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Hydrological connectivity is crucial for the healthy operation of wetland ecosystems. However, the current design of ecological corridors in wetland biodiversity networks is mostly based on species migration resistance, neglecting the important role of hydrological connectivity. How to incorporate hydrological connectivity into the wetland ecological corridor system (ECS) is still unclear. To answer the question, we proposed a framework for constructing a wetland ECS with the goal of improving conservation value of previously identified wetland biodiversity hotspots based on hydrological connectivity. In the proposed framework, we clarified the function-level-dimension of each corridor based on the dynamics of conservation value of biodiversity hotspots, the hierarchical classification of rivers and the dimension of hydrological connectivity. Then we determined the spatial distribution and functional zoning of the corridors by least cost model (LCM) using indicators that reflect wetland hydrological connectivity resistance, including water coverage, water use efficiency of vegetation, and land use suitability. The results are as follows: (1) to improve the overall hydrological connectivity and conservation value of biodiversity hotspots, 25 corridors should be constructed for vertical hydrological connectivity (with 3 for maintaining the status quo, 6 for improving and 16 for restoring connectivity) and 3 corridors should be constructed for lateral hydrological connectivity; (2) total area of all corridors are 11 km2, accounting for 6.79% of the study area (2.47% of core zone and 4.32% of buffer zone); (3) low suitability areas of hydrological vegetation gradient (HVG) are the most extensive, followed by low suitability areas of land use/cover change (LUCC) and the average fraction coverage of water surface (AFCW), accounting for 65.08%, 47.87% and 6.76% of the corridor coverage, respectively. The proposed framework of constructing wetland ECS in this study has the potential to provide the post-2020 global biodiversity framework and sustainable development goals with specific technical support and more targeted-control strategies for building a hydrological connected wetland biodiversity network.
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BACKGROUND: In the field of ornamental horticulture, phenotypic mutations, particularly in leaf color, are of great interest due to their potential in developing new plant varieties. The introduction of variegated leaf traits in plants like Heliopsis helianthoides, a perennial herbaceous species with ecological adaptability, provides a rich resource for molecular breeding and research on pigment metabolism and photosynthesis. We aimed to explore the mechanism of leaf variegation of Heliopsis helianthoides (using HY2021F1-0915 variegated mutant named HY, and green-leaf control check named CK in 2020 April, May and June) by analyzing the transcriptome and metabolome. RESULTS: Leaf color and physiological parameters were found to be significantly different between HY and CK types. Chlorophyll content of HY was lower than that of CK samples. Combined with the result of Weighted Gene Co-expression Network Analysis (WGCNA), 26 consistently downregulated differentially expressed genes (DEGs) were screened in HY compared to CK subtypes. Among the DEGs, 9 genes were verified to be downregulated in HY than CK by qRT-PCR. The reduction of chlorophyll content in HY might be due to the downregulation of FSD2. Low expression level of PFE2, annotated as ferritin-4, might also contribute to the interveinal chlorosis of HY. Based on metabolome data, differential metabolites (DEMs) between HY and CK samples were significantly enriched on ABC transporters in three months. By integrating DEGs and DEMs, they were enriched on carotenoids pathway. Downregulation of four carotenoid pigments might be one of the reasons for HY's light color. CONCLUSION: FSD2 and PFE2 (ferritin-4) were identified as key genes which likely contribute to the reduced chlorophyll content and interveinal chlorosis observed in HY. The differential metabolites were significantly enriched in ABC transporters. Carotenoid biosynthesis pathway was highlighted with decreased pigments in HY individuals. These findings not only enhance our understanding of leaf variegation mechanisms but also offer valuable insights for future plant breeding strategies aimed at preserving and enhancing variegated-leaf traits in ornamental plants.
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Metaboloma , Hojas de la Planta , Transcriptoma , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Clorofila/metabolismo , Regulación de la Expresión Génica de las Plantas , Perfilación de la Expresión Génica , Pigmentación/genéticaRESUMEN
BACKGROUND: As a screening method, inaccuracies in noninvasive prenatal screening (NIPS) exist, which are often attributable to biological factors. One such factor is the history of transplantation. However, there are still limited reports on such NIPS cases. METHODS: We report an NIPS case of a pregnant woman who had received a stem cell transplant from a male donor. To determine the karyotype in the woman's original cell, we performed chromosome microarray analysis (CMA) on her postnatal blood and oral mucosa. To comprehensively estimate the cell-free DNA (cfDNA) composition, we further performed standard NIPS procedures on the postnatal plasma. Moreover, we reviewed all published relevant NIPS case reports about pregnant women with transplantation history. RESULTS: NIPS showed a low-risk result for common trisomies with a fetal fraction of 65.80%. CMA on maternal white blood cells showed a nonmosaic male karyotype, while the oral mucosa showed a nonmosaic female karyotype. The proportion of donor's cfDNA in postnatal plasma was 94.73% based on the Y-chromosome reads ratio. The composition of cfDNA in maternal plasma was estimated as follows: prenatally, 13.60% maternal, 65.80% donor, and 20.60% fetal/placental, whereas postnatally, 5.27% maternal and 94.73% donor. CONCLUSIONS: This study expanded our understanding of the influence of stem cell transplantation on NIPS, allowing us to optimize NIPS management for these women.
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Ácidos Nucleicos Libres de Células , Pruebas Prenatales no Invasivas , Humanos , Femenino , Embarazo , Masculino , Adulto , Ácidos Nucleicos Libres de Células/genética , Ácidos Nucleicos Libres de Células/sangre , Pruebas Prenatales no Invasivas/métodos , Trasplante de Células Madre , Donantes de Tejidos , Trisomía/genéticaRESUMEN
The human cerebral cortex, pivotal for advanced cognitive functions, is composed of six distinct layers and dozens of functionally specialized areas1,2. The layers and areas are distinguished both molecularly, by diverse neuronal and glial cell subtypes, and structurally, through intricate spatial organization3,4. While single-cell transcriptomics studies have advanced molecular characterization of human cortical development, a critical gap exists due to the loss of spatial context during cell dissociation5,6,7,8. Here, we utilized multiplexed error-robust fluorescence in situ hybridization (MERFISH)9, augmented with deep-learning-based cell segmentation, to examine the molecular, cellular, and cytoarchitectural development of human fetal cortex with spatially resolved single-cell resolution. Our extensive spatial atlas, encompassing 16 million single cells, spans eight cortical areas across four time points in the second and third trimesters. We uncovered an early establishment of the six-layer structure, identifiable in the laminar distribution of excitatory neuronal subtypes by mid-gestation, long before the emergence of cytoarchitectural layers. Notably, while anterior-posterior gradients of neuronal subtypes were generally observed in most cortical areas, a striking exception was the sharp molecular border between primary (V1) and secondary visual cortices (V2) at gestational week 20. Here we discovered an abrupt binary shift in neuronal subtype specification at the earliest stages, challenging the notion that continuous morphogen gradients dictate mid-gestation cortical arealization6,10. Moreover, integrating single-nuclei RNA-sequencing and in situ whole transcriptomics revealed an early upregulation of synaptogenesis in V1-specific Layer 4 neurons, suggesting a role of synaptogenesis in this discrete border formation. Collectively, our findings underscore the crucial role of spatial relationships in determining the molecular specification of cortical layers and areas. This work not only provides a valuable resource for the field, but also establishes a spatially resolved single-cell analysis paradigm that paves the way for a comprehensive developmental atlas of the human brain.
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Lipopolysaccharide (LPS) is known to elicit a robust immune response. This study aimed to investigate the impact of LPS on the transcriptome of human nasal epithelial cells (HNEpC). HNEpC were cultured and stimulated with LPS (1 µg/mL) or an equivalent amount of normal culture medium. Subsequently, total RNA was extracted, purified, and sequenced using next-generation RNA sequencing technology. Differentially expressed genes (DEGs) were identified and subjected to functional enrichment analysis. A protein-protein interaction (PPI) network of DEGs was constructed, followed by Ingenuity Pathway Analysis (IPA) to identify molecular pathways influenced by LPS exposure on HNEpC. Validation of key genes was performed using quantitative real-time PCR (qRT-PCR). A total of 97 DEGs, comprising 48 up-regulated genes and 49 down-regulated genes, were identified. Results from functional enrichment analysis, PPI, and IPA indicated that DEGs were predominantly enriched in chemokine-related signaling pathways. Subsequent qRT-PCR validation demonstrated significant upregulation of key genes in these pathways in LPS-treated HNEpC compared to control cells. In conclusion, LPS intervention profoundly altered the transcriptome of HNEpC, potentially exacerbating inflammatory responses through the activation of chemokine-related signaling pathways.
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Perfilación de la Expresión Génica , Lipopolisacáridos , Humanos , Perfilación de la Expresión Génica/métodos , Lipopolisacáridos/farmacología , Transcriptoma , Transducción de Señal/genética , Células Epiteliales , Quimiocinas/genética , Biología Computacional/métodosRESUMEN
BACKGROUND: SERPINB2, a biomarker of Type-2 (T2) inflammatory processes, has been described in the context of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also correlated with T2 inflammation and elevated 15LO1 induced by IL-4/13 in nasal epithelial cells. The aim of this study was to evaluate the expression and location of SERPINB2 in nasal epithelial cells (NECs) and determine whether SERPINB2 regulates 15LO1 and downstream T2 markers in NECs via STAT6 signalling. METHODS: SERPINB2 gene expression in bulk and single-cell RNAseq database was analysed by bioinformatics analysis. SERPINB2, 15LO1 and other T2 markers were evaluated from CRSwNP and HCs NECs. The colocalization of SERPINB2 and 15LO1 was evaluated by immunofluorescence. Fresh NECs were cultured at an air-liquid interface with or without IL-13, SERPINB2 Dicer-substrate short interfering RNAs (DsiRNAs) transfection, exogenous SERPINB2, 15-HETE recombinant protein and pSTAT6 inhibitors. 15LO1, 15-HETE and downstream T2 markers were analysed by qRT-PCR, western blot and ELISA. RESULTS: SERPINB2 expression was increased in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues and positively correlated with 15LO1 and other downstream T2 markers. SERPINB2 was predominantly expressed by epithelial cells in NP tissue and was colocalized with 15LO1. In primary NECs in vitro, SERPINB2 expression was induced by IL-13. Knockdown or overexpression SERPINB2 decreased or enhanced expression of 15LO1 and 15-HETE in NECs, respectively, in a STAT6-dependent manner. SERPINB2 siRNA also inhibited the expression of the 15LO1 downstream genes, such as CCL26, POSTN and NOS2. STAT6 inhibition similarly decreased SERPINB2-induced 15LO1. CONCLUSIONS: SERPINB2 is increased in NP epithelial cells of eosinophilic CRSwNP (eCRSwNP) and contributes to T2 inflammation via STAT6 signalling. SERPINB2 could be considered a novel therapeutic target for eCRSwNP.
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Células Epiteliales , Pólipos Nasales , Rinitis , Factor de Transcripción STAT6 , Transducción de Señal , Sinusitis , Humanos , Factor de Transcripción STAT6/metabolismo , Factor de Transcripción STAT6/genética , Pólipos Nasales/metabolismo , Pólipos Nasales/patología , Pólipos Nasales/inmunología , Sinusitis/metabolismo , Sinusitis/patología , Sinusitis/inmunología , Rinitis/metabolismo , Rinitis/patología , Enfermedad Crónica , Células Epiteliales/metabolismo , Inhibidor 2 de Activador Plasminogénico/metabolismo , Inhibidor 2 de Activador Plasminogénico/genética , Femenino , Masculino , Quimiocina CCL26/metabolismo , Quimiocina CCL26/genética , Adulto , Persona de Mediana Edad , Eosinofilia/metabolismo , Eosinofilia/patología , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , Mucosa Nasal/inmunología , Regulación de la Expresión Génica , RinosinusitisRESUMEN
Optical genome mapping (OGM) has been known as an all-in-one technology for chromosomal aberration detection. However, there are also aberrations beyond the detection range of OGM. This study aimed to report the aberrations missed by OGM and analyze the contributing factors. OGM was performed by taking both GRCh37 and GRCh38 as reference genomes. The OGM results were analyzed in blinded fashion and compared to standard assays. Quality control (QC) metrics, sample types, reference genome, effective coverage and classes and locations of aberrations were then analyzed. In total, 154 clinically reported variations from 123 samples were investigated. OGM failed to detect 10 (6.5%, 10/154) aberrations with GRCh37 assembly, including five copy number variations (CNVs), two submicroscopic balanced translocations, two pericentric inversion and one isochromosome (mosaicism). All the samples passed pre-analytical and analytical QC. With GRCh38 assembly, the false-negative rate of OGM fell to 4.5% (7/154). The breakpoints of the CNVs, balanced translocations and inversions undetected by OGM were located in segmental duplication (SD) regions or regions with no DLE-1 label. In conclusion, besides variations with centromeric breakpoints, structural variations (SVs) with breakpoints located in large repetitive sequences may also be missed by OGM. GRCh38 is recommended as the reference genome when OGM is performed. Our results highlight the necessity of fully understanding the detection range and limitation of OGM in clinical practice.
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Fine particulate matter (PM2.5) represents a prevalent environmental pollutant in the atmosphere, capable of exerting deleterious effects on human health. Numerous studies have indicated a correlation between PM2.5 exposure and the development of chronic upper airway inflammatory diseases. The objective of this study was to investigate the impact of PM2.5 on the transcriptome of fibroblasts derived from nasal mucosa. Initially, nasal mucosa-derived fibroblasts were isolated, cultured, and subsequently stimulated with PM2.5 (100 µg/mL) or an equivalent volume of normal culture medium for a duration of 24 h. Following this, total RNA from these cells was extracted, purified, and subjected to sequencing using next-generation RNA sequencing technology. Differentially expressed genes (DEGs) were then identified and utilized for functional enrichment analysis. A protein-protein interaction (PPI) network of DEGs was constructed, and validation of key genes and proteins was carried out using quantitative real-time PCR and ELISA methods. Results revealed 426 DEGs, comprising 276 up-regulated genes and 150 down-regulated genes in nasal mucosa-derived fibroblasts treated with PM2.5 compared to control cells. Functional enrichment analysis indicated that DEGs were predominantly associated with inflammation-related pathways, including the IL-17 signaling pathway. In alignment with this, PPI analysis highlighted that hub genes were primarily involved in the regulation of the IL-17 signaling pathway. Subsequent validation through quantitative real-time PCR and ELISA confirmed significant alterations in the relative expressions of IL-17 signaling pathway-related genes and concentrations of IL-17 signaling pathway related proteins in nasal mucosa-derived fibroblasts treated with PM2.5 compared to control cells. In conclusion, PM2.5 intervention substantially altered the transcriptome of nasal mucosa-derived fibroblasts. Furthermore, PM2.5 has the potential to exacerbate the inflammatory responses of these fibroblasts by modulating the expression of key genes in the IL-17 signaling pathway.
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Interleucina-17 , Mucosa Nasal , Humanos , Interleucina-17/metabolismo , Mucosa Nasal/metabolismo , Transducción de Señal , Material Particulado/metabolismo , Fibroblastos/metabolismoRESUMEN
BACKGROUND AND AIMS: Hearing loss is a common sensorineural disease with genetic heterogeneity. More than 140 genes are known to cause hereditary hearing loss. We aim to uncover the etiologies of hearing loss and provide patients with reasonable reproductive choices. MATERIALS AND METHODS: Total 825 participants were recruited, including 74 individuals, 47 couples, and 219 families, to identify the molecular etiologies of hearing loss using next-generation sequencing (NGS). Novel mutations were verified with a minigene splicing assay and the construction of three-dimensional protein models. RESULTS: A positive molecular diagnosis was obtained for 244 patients, a rate of 63.05 %. Total 470 mutations were identified in 18 causative genes in positive patients. The most common genes mutated were GJB2 and SLC26A4. 47 novel mutations were identified. Further analysis predicted that two splicing mutations would cause abnormal mRNA splicing and three missense mutations would affect the protein structure. The results of prenatal diagnosis showed that the genotypes of 15 fetuses were the same as the probands. CONCLUSION: Our findings expand the mutation spectrum of hearing loss and highlight the importance of genetic diagnosis and prenatal diagnosis to allow accurate and personalized guidance for those at high risk of deafness.
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Sordera , Pérdida Auditiva Sensorineural , Pérdida Auditiva , Embarazo , Femenino , Humanos , Conexinas/genética , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/genética , Pruebas Genéticas , Sordera/diagnóstico , Sordera/genética , Pérdida Auditiva Sensorineural/genética , Mutación , Secuenciación de Nucleótidos de Alto Rendimiento/métodosRESUMEN
BACKGROUND: It remains controversial whether prenatal screening or diagnostic testing should be offered to fetuses with nasal bone (NB) absence or hypoplasia, and there are no studies comparing the yield of chromosomal microarray analysis (CMA) to non-invasive prenatal screening (NIPS). The aim of this study was to evaluate the residual risk of clinically significant copy number variations (CNVs) in fetuses with NB absence or hypoplasia after excluding theoretically NIPS-detectable abnormalities, and to assess their clinical outcomes. METHODS: This prospective study encompassed 400 fetuses with NB absence or hypoplasia undergoing CMA testing between 2015 and 2022. Clinically significant CMA findings were categorized into three subgroups, including three-NIPS-detectable (trisomies 21, 18 and 13), five-NIPS-detectable (trisomies 21, 18 and 13 and sex chromosome aneuploidies) and genome-wide NIPS-detectable (variants over 7 Mb). We calculated the theoretical residual risk and compared it with the results of a control cohort of low-risk pregnancies. We further evaluated their clinical outcomes. RESULTS: The overall diagnostic yield in our cohort was 7.8% (31/400). The detection rate of clinically significant CMA findings in fetuses with non-isolated NB absence or hypoplasia was significantly higher than that in fetuses with isolated NB absence or hypoplasia (20.0% vs. 6.6%, P =.005). The theoretical residual risks in all NIPS models were significantly higher when compared with the control cohort. The normal infant rate in fetuses with normal CMA results was 97.9% (323/330), and a significant higher incidence was observed in fetuses with isolated NB absence or hypoplasia compared with non-isolated NB absence or hypoplasia (98.4% vs. 91.7%, P =.028). CONCLUSIONS: The residual risk of clinically significant CNVs in fetuses with NB absence or hypoplasia following the exclusion of theoretically NIPS-detectable findings was higher than that in low-risk pregnancies. This risk should be considered in genetic counseling to make a more comprehensive and precise choice regarding prenatal genetic testing.
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Variaciones en el Número de Copia de ADN , Diagnóstico Prenatal , Embarazo , Femenino , Humanos , Diagnóstico Prenatal/métodos , Trisomía , Estudios Prospectivos , Hueso Nasal/anomalías , Feto/anomalías , Análisis por Micromatrices , Aberraciones CromosómicasRESUMEN
Congenital contractural arachnodactyly (CCA) is a rare connective tissue disorder characterized by arachnodactyly, multiple joint contractures, progressive kyphoscoliosis, pectus deformity and abnormal crumpled ears. FBN2 is the only gene currently known to be associated with CCA. In this study, we report on a prenatal case presented with skeletal, cardiac and spinal malformations. And his father had elongated limbs, contractures of the proximal interphalangeal joints, high myopia and scoliosis. We conducted whole exome sequencing (WES) on the fetus-parental trio and a heterozygous variant (hg19 chr5:127,673,685, c.3598 + 4A > G, NM_001999.4) in intron 27 of the FBN2 gene was successfully identified, inherited from the father. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate the potential splicing effect of this variant, which confirmed that the variant caused a deletion of exon 27 (126 bp) by disrupting the splice-donor site and destroyed the 17th calcium-binding epidermal growth factor-like (cbEGF) domain. Our research not only finds the etiology of the disease in affected individuals and expands the mutation spectrum of FBN2 gene, but also provides genetic counseling and fertility guidance for this family.
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Objectives: Mass vaccination campaigns can rapidly increase the vaccination rate for the COVID-19 vaccine, the establishment of mass vaccination centers is indispensable. At the beginning of March 2021, China began to carry out COVID-19 vaccination activities nationwide. Here, we aimed to evaluate the criteria established by mass vaccination centers, COVID-19 vaccination experience, the incidence of adverse events following immunization and opinions. Methods: We describe the layout and functioning of Nan'an District mass vaccination center, the working mechanism, experience and effectiveness. Distribution of COVID-19 vaccine vaccination and adverse events following immunization reported in the mass vaccination center of Nan'an District were evaluated. Results: From March 26, 2021 to April 28, 2022, the mass vaccination center has inoculated about 381,364 doses of COVID-19 vaccine to the population. The study found that the incidence of adverse events following immunization (AEFI) was very low (1.04/100000). The chances of having AEFI were significantly higher in COVID-19 vaccine (CHO cell) than COVID-19 vaccine (Vero cell). Conclusion: The mass vaccination center was running successfully. It was effective and safe, providing vaccination services and increasing COVID-19 vaccination rates among the population. The experience of the mass vaccination center for COVID-19 in China can provide a reference for other countries and regions to carry out COVID-19 vaccination.
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COVID-19 , Vacunación Masiva , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/etiología , Vacunas contra la COVID-19/administración & dosificación , Inmunización/efectos adversos , Vacunación/efectos adversosRESUMEN
BACKGROUND: Emerging studies suggest that whole genome sequencing provides additional diagnostic yield of genomic variants when compared with chromosomal microarray analysis in the etiologic diagnosis of infants and children with suspected genetic diseases. However, the application and evaluation of whole genome sequencing in prenatal diagnosis remain limited. OBJECTIVE: This study aimed to evaluate the accuracy, efficacy, and incremental yield of whole genome sequencing in comparison with chromosomal microarray analysis for routine prenatal diagnosis. STUDY DESIGN: In this prospective study, a total of 185 unselected singleton fetuses with ultrasound-detected structural anomalies were enrolled. In parallel, each sample was subjected to whole genome sequencing and chromosomal microarray analysis. Aneuploidies and copy number variations were detected and analyzed in a blinded fashion. Single nucleotide variations and insertions and deletions were confirmed by Sanger sequencing, and trinucleotide repeats expansion variants were verified using polymerase chain reaction plus fragment-length analysis. RESULTS: Overall, genetic diagnoses using whole genome sequencing were obtained for 28 (15.1%) cases. Whole genome sequencing not only detected all these aneuploidies and copy number variations in the 20 (10.8%) diagnosed cases identified by chromosomal microarray analysis, but also detected 1 case with an exonic deletion of COL4A2 and 7 (3.8%) cases with single nucleotide variations or insertions and deletions. In addition, 3 incidental findings were detected including an expansion of the trinucleotide repeat in ATXN3, a splice-sites variant in ATRX, and an ANXA11 missense mutation in a case of trisomy 21. CONCLUSION: Compared with chromosomal microarray analysis, whole genome sequencing increased the additional detection rate by 5.9% (11/185). Using whole genome sequencing, we detected not only aneuploidies and copy number variations, but also single nucleotide variations and insertions and deletions, trinucleotide repeat expansions, and exonic copy number variations with high accuracy in an acceptable turnaround time (3-4 weeks). Our results suggest that whole genome sequencing has the potential to be a new promising prenatal diagnostic test for fetal structural anomalies.
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Variaciones en el Número de Copia de ADN , Ultrasonografía Prenatal , Embarazo , Femenino , Lactante , Niño , Humanos , Estudios Prospectivos , Primer Trimestre del Embarazo , Diagnóstico Prenatal/métodos , Aneuploidia , Secuenciación Completa del Genoma , Análisis por Micromatrices , Aberraciones CromosómicasRESUMEN
Objective:To investigate the safety and effectiveness of the ethmoid artery pedicled septal floor mucosal flap in repair of postoperative cerebrospinal fluid leakage after transsphenoidal pituitary tumor surgery.Methods: The clinical data of 6 patients with cerebrospinal fluid leak in Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2011 to June 2022. In 6 patients with postoperative cerebrospinal fluid leakage after transsphenoidal pituitary surgery, the bilateral posterior septal arteries were sacrificed due to the endoscopic transsphenoidal expanded approach, so the ethmoid artery pedicled septal floor mucosal flaps were adopted.Results:All patients had good growth of the mucosal flaps during postoperative follow-up without recurrent cerebrospinal fluid leakage. Conclusion:Cerebrospinal fluid leakage is still one of the postoperative complications of pituitary surgery. For patients with bilateral posterior septal arteries sacrificed through the transsphenoidal approach, when the classic posterior septal artery pedicled mucosal flap is not available, the ethmoid artery pedicled septal floor mucosal flap is one of the alternative methods.
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Neoplasias Hipofisarias , Base del Cráneo , Humanos , Base del Cráneo/cirugía , China , Pérdida de Líquido Cefalorraquídeo/cirugía , Complicaciones Posoperatorias , Membrana Mucosa , Arterias , Estudios Retrospectivos , Neoplasias Hipofisarias/cirugíaRESUMEN
PURPOSE: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a chronic sinonasal inflammatory disease characterized histologically by hyperplastic nasal epithelium and epithelial cells proliferation. Cysteine-rich angiogenic inducer 61 (CYR61) acts as a positive regulator of cell cycle process. Cyclin D1 (CCND1) and c-Myc play key roles in the processes of cell cycle and cell growth. The purpose of our research was to explore the expression and roles of CYR61, CCND1 and c-Myc in CRSwNP. METHODS: FeaturePlot and vlnPlot functions embedded in the seurat package (version 4.1.1) of R software (version 4.2.0) were applied to explore the cellular distribution of CYR61, CCND1 and c-Myc in the single-cell RNA sequencing (scRNA-seq) dataset of nasal tissue samples. CYR61, CCND1 and c-Myc immunolabeling and mRNA levels in nasal tissue samples were assessed by immunohistochemistry and real-time PCR. Co-localization of CYR61, CCND1 and c-Myc with basal epithelial cell marker P63 was assayed using double-label immunofluorescence staining. Furthermore, we collected and cultured human nasal epithelial cells (HNEC) to assess the regulation and role of CYR61 in vitro study. RESULTS: CYR61, CCND1 and c-Myc were primarily expressed by nasal epithelial cells. Significant upregulation of CYR61, CCND1 and c-Myc positive cells and increased levels of CYR61, CCND1 and c-Myc mRNA were found in nasal polyps in comparison to control samples. Of note, CYR61 mRNA and protein levels were altered by SEB, LPS, IFN-γ, IL-13, IL-17A and TGF-ß1 in HNEC. In addition, CYR61 intervention could increase CCND1 and c-Myc mRNA and protein levels to promote HNEC proliferation, and siRNA against ITGA2 (si-ITGA2) could reverse CYR61 induced upregulation of CCND1 and c-Myc mRNA and protein levels in HNEC and cell proliferation of HNEC. CONCLUSIONS: CYR61, CCND1 and c-Myc were primarily expressed by epithelial cells in nasal mucosa. CYR61, CCND1 and c-Myc expression levels were increased in CRSwNP compared with controls. CYR61 could interact with ITGA2 to enhance HNEC proliferation via upregulating CCND1 and c-Myc levels in the HNEC, leading to hyperplastic nasal epithelium in CRSwNP.
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Proteína 61 Rica en Cisteína , Pólipos Nasales , Rinitis , Humanos , Proliferación Celular , Enfermedad Crónica , Ciclina D1/genética , Ciclina D1/metabolismo , Células Epiteliales/metabolismo , Mucosa Nasal/metabolismo , Pólipos Nasales/metabolismo , Rinitis/metabolismo , ARN Mensajero/metabolismo , Proteína 61 Rica en Cisteína/metabolismoRESUMEN
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common sinonasal inflammatory disorder with high heterogeneity. Increasing evidence have indicated that the infiltration of macrophages especially M2 macrophages play pivotal roles in the pathogenesis of CRSwNP, but the underlying mechanisms remain undetermined. This study sought to identify potential biomarkers related to M2 macrophages in CRSwNP. Methods: The expression datasets of GSE136825 and GSE179265 were download from Gene Expression Omnibus (GEO) database and merged. Then, CIBERSORT and weighted gene co-expression network analysis (WGCNA) algorithms were applied to identify M2 macrophage-related gene modules. Thereafter, differentially expressed genes (DEGs) related to M2 macrophages were selected to perform functional enrichment analyses. A protein-protein interaction (PPI) network was built to identify hub genes and quantitative real-time reverse transcriptions PCR was used to verify the bioinformatics results. Results: A total of 92 DEGs associated with M2 macrophages were identified for further analysis. The results of Gene ontology (GO) and Kyoto Encyclopedia of genes and genomes (KEGG) analyses illustrated that M2 macrophage-associated DEGs primarily enriched in immune responses and extracellular matrix structure. PPI network analysis identified 18 hub genes related to M2 macrophages that might be pivotal in the pathogenesis of CRSwNP. After verification, AIF1, C1QA, C1QB, C3AR1, CCR1, CD163, CD4, CD53, CD86, CSF1R, CYBB, FCER1G, FCGR3A, IL10RA, ITGB2, LAPTM5, PLEK, TYROBP were identified as potential M2 macrophage-related biomarkers for CRSwNP. Conclusion: These findings yield new insights into the hub genes and mechanisms related to M2 macrophages in the pathogenesis of CRSwNP. Further studies of these hub genes would help better understand the disease progression and identify potential treatment targets.
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Pólipos Nasales , Sinusitis , Humanos , Pólipos Nasales/genética , Sinusitis/genética , Genes fms , Enfermedad Crónica , MacrófagosRESUMEN
BACKGROUND: Multiple sulfatase deficiency (MSD) (MIM#272200) is an ultra-rare autosomal recessive lysosomal storage disorder caused by mutation of the Sulfatase Modifying Factor 1 (SUMF1) gene. METHODS: Herein, we report an eight-year-old boy with a late infantile form of multiple sulfatase deficiency. A combination of copy-number variation sequencing (CNV-seq) and whole-exome sequencing (WES) were used to analyze the genetic cause for the MSD patient. RESULTS: Our results, previously not seen in China, show a novel compound heterozygous mutation with one allele containing a 240.55 kb microdeletion on 3p26.1 encompassing the SETMAR gene and exons 4-9 of the SUMF1 gene, and the other allele containing a novel missense mutation of c.671G>A (p.Arg224Gln) in the SUMF1 gene. Both were inherited from the proband's unaffected parents, one from each. Bioinformatics analyses show the novel variation to be "likely pathogenic." SWISS-MODEL analysis shows that the missense mutation may alter the three-dimensional (3D) structure. CONCLUSIONS: In summary, this study reported a novel compound heterozygous with microdeletion in SUMF1 gene, which has not been reported in China. The complex clinical manifestations of MSD may delay diagnosis; however, molecular genetic analysis of the SUMF1 gene can be performed to help obtain an early diagnosis.
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Enfermedad por Deficiencia de Múltiples Sulfatasas , Masculino , Humanos , Niño , Enfermedad por Deficiencia de Múltiples Sulfatasas/genética , Enfermedad por Deficiencia de Múltiples Sulfatasas/diagnóstico , Sulfatasas/genética , Mutación/genética , Mutación Missense , Biología Computacional , N-Metiltransferasa de Histona-Lisina/genética , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/genéticaRESUMEN
OBJECTIVE: To explore the genetic basis for fetuses with renal anomalies. METHODS: Genomic DNA of four fetuses and their parents was extracted from amniotic fluid and peripheral blood samples and subjected to whole genome sequencing. Candidate variants were predicted according to the American College of Medical Genetics and Genomics (ACMG) guidelines and validated by SNP-array and Sanger sequencing. RESULTS: Two fetuses were found to carry a 1.45 Mb pathogenic microdeletion in 17q12 and a pathogenic 1.85 Mb microduplication at 1q21.1-21.2, respectively. One fetus was found to harbor compound heterozygous variants c.8301del (p.Asn2768Thrfs*18) and c.4481del (p.Asn1494Thrfs*6) of the PKHD1 gene, which were predicted to be pathogenic. And one fetus has harbored homozygous c.1372dup (p.Thr458Asnfs*5) variants of the BBS12 gene, which was predicted to be likely pathogenic. All variants were validated by Sanger sequencing. CONCLUSION: Whole genome sequencing can enable efficient prenatal diagnosis for fetuses with renal anomalies with high accuracy.
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Feto , Diagnóstico Prenatal , Femenino , Feto/anomalías , Humanos , Embarazo , Secuenciación Completa del GenomaRESUMEN
BACKGROUND: The competing endogenous RNA (ceRNA) activity of circular RNAs (circRNAs) has been implicated in the pathogenesis of cancers, including esophageal squamous cell carcinoma (ESCC). Here, we identified the ceRNA mechanism of circ_0000654 regulation in ESCC. METHODS: The levels of circ_0000654, E2F transcription factor 3 (E2F3), and microRNA (miR)-375 were gauged by quantitative real-time PCR (qRT-PCR) and western blot. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell apoptosis was detected by flow cytometry. Cell colony formation was tested by colony formation assay. Dual-luciferase reporter, RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to confirm the direct relationship between miR-375 and circ_0000654 or E2F3. Xenograft model assays were used to evaluate the effect of circ_0000654 in vivo. RESULTS: Circ_0000654 and E2F3 were upregulated in ESCC. Circ_0000654 depletion enhanced cell apoptosis and hindered cell proliferation and glycolysis in vitro, as well as weakened tumor growth in vivo. Increased expression of E2F3 counteracted the effects of circ_0000654 depletion. Mechanistically, E2F3 was a target of miR-375, and circ_0000654 modulated E2F3 expression through sequestering miR-375. Furthermore, miR-375 upregulation phenocopied circ_0000654 knockdown in inhibiting ESCC progression. CONCLUSION: Our findings identify a new circ_0000654/miR-375/E2F3 ceRNA crosstalk for the oncogenic role of circ_0000654 in ESCC and establish a notion that targeting circ_0000654 and its pathways may have the potential to improve ESCC outcome.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Factor de Transcripción E2F3/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
Wetlands are important ecosystems for biodiversity preservation and environmental regulation. However, the integrity of wetland ecosystems has been seriously compromised and damaged due to the reckless and indiscriminate exploitation of wetland resources during economic development by human society. Hence, wetland restoration has now attracted wide attention. Understanding wetland restoration suitability and its relationship with river grade and river distance is an important step in further implementing wetland restoration and ensuring an orderly wetland development and utilization. In this study, wetland restoration suitability is evaluated combining natural and human factors. Taking its result as an important basis, the spatial distribution characteristics of different levels of wetland restoration suitability are discussed for the studied region; the percentage distribution of different levels of wetland restoration suitability is analyzed for 10 km long buffer zones of rivers of different grades, and the association between the distribution of different levels of wetland restoration suitability and the river distance (2, 4, 6, 8, and 10 km) is also analyzed for different buffer zones of rivers in different grades. Our findings show that the spatial distribution of wetland restoration suitability is closely associated with the grade of rivers and the distance of the wetland patches from the river. The higher the river grade, the higher the percentage of the wetland with high restoration suitability within the same river distance. The percentage of wetlands with high restoration suitability has shown a notably decreasing trend as the river distance increases for the areas beside rivers of all grades, while the percentage of a wetland area with relatively high restoration suitability tends to increase as the river distance increases for the areas beside rivers of grade I and II and does not have a noticeable trend to change as the river distance changes for the area beside rivers of other grades. Results of this can provide technical support for wetland restoration suitability evaluation for plain areas, a spatial reference for wetland restoration prioritizing, and an orderly wetland development and utilization in future studies and planning.