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Prenatal diagnostic testing of amniotic fluid, chorionic villi, or more rarely, fetal cord blood is recommended following a positive or unreportable noninvasive cell-free fetal DNA test, abnormal maternal biochemical serum screen, abnormal ultrasound, or increased genetic risk for a cytogenomic abnormality based on family history. Although chromosomal microarray is recommended as the first-tier prenatal diagnostic test, in practice, multiple assays are often assessed in concert to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive. Optical genome mapping (OGM) is an emerging technique with application for prenatal diagnosis because of its ability to detect and resolve, in a single assay, all classes of pathogenic cytogenomic aberrations. In an effort to characterize the potential of OGM as a novel alternative to traditional standard of care (SOC) testing of prenatal samples, OGM was performed on a total of 200 samples representing 123 unique cases, which were previously tested with SOC methods (92/123 = 74.7% cases tested with at least two SOCs). OGM demonstrated an overall accuracy of 99.6% when compared with SOC methods, a positive predictive value of 100%, and 100% reproducibility between sites, operators, and instruments. The standardized workflow, cost-effectiveness, and high-resolution cytogenomic analysis demonstrate the potential of OGM to serve as a first-tier test for prenatal diagnosis.
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Noradrenergic neurons play a crucial role in the functioning of the nervous system. They formed compact small clusters in the central nervous system. To target noradrenergic neurons in combination with viral tracing and achieve cell-type specific functional manipulation using chemogenetic or optogenetic tools, new transgenic animal lines are needed, especially rat models for their advantages in large body size with facilitating easy operation, physiological parameter monitoring, and accommodating complex behavioral and cognitive studies. In this study, we successfully generated a transgenic rat strain capable of expressing Cre recombinase under the control of the dopamine beta-hydroxylase (DBH) gene promoter using the CRISPR-Cas9 system. Our validation process included co-immunostaining with Cre and DBH antibodies, confirming the specific expression of Cre recombinase. Furthermore, stereotaxic injection of a fluorescence-labeled AAV-DIO virus illustrated the precise Cre-loxP-mediated recombination activity in noradrenergic neurons within the locus coeruleus (LC). Through crossbreeding with the LSL-fluorescence reporter rat line, DBH-Cre rats proved instrumental in delineating the position and structure of noradrenergic neuron clusters A1, A2, A6 (LC), and A7 in rats. Additionally, our specific activation of the LC noradrenergic neurons showed effective behavioral readout using chemogenetics of this rat line. Our results underscore the effectiveness and specificity of Cre recombinase in noradrenergic neurons, serving as a robust tool for cell-type specific targeting of small-sized noradrenergic nuclei. This approach enhances our understanding of their anatomical, physiological, and pathological roles, contributing to a more profound comprehension of noradrenergic neuron function in the nervous system.
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Neuronas Adrenérgicas , Sistemas CRISPR-Cas , Dopamina beta-Hidroxilasa , Integrasas , Ratas Transgénicas , Animales , Integrasas/genética , Integrasas/metabolismo , Neuronas Adrenérgicas/metabolismo , Ratas , Dopamina beta-Hidroxilasa/genética , Dopamina beta-Hidroxilasa/metabolismo , Locus Coeruleus/metabolismo , Masculino , Ratas Sprague-DawleyRESUMEN
Soft tissue integration around titanium (Ti) implants is weaker than that around natural teeth, compromising long-term success of Ti implants. Carbon monoxide (CO) possesses distinctive therapeutic properties, rendering it as a highly promising candidate for enhancing STI. However, achieving controlled CO generation at the STI interface remains challenging. Herein, a controlled CO-releasing dual-function coating was constructed on Ti surfaces. Under near-infrared (NIR) irradiation, the designed surface could actively accelerate CO generation for antibiosis against both aerobic and anaerobic bacteria. More importantly, in the absence of NIR, the slow release of CO induces macrophage polarization from pro-inflammatory phenotype towards pro-regenerative phenotype. In a rat implantation model with induced infection, the designed surface effectively controlled the bacterial infection, alleviates accompanying inflammation and modulated immune microenvironment, leading to enhanced STI. Single-cell sequencing revealed that the coating alters the cytokine profile within the soft tissue, thereby influencing cellular functions. Differentially expressed genes in macrophages are highly enriched in the PIK3-Akt pathway. Furthermore, the cellular communication between fibroblasts and macrophages was significantly enhanced through the CXCL12/CXCL14/CXCR4 and CSF1-CSF1R ligand-receptor pair. These findings indicate that our coating showed an appealing prospect for enhancing STI around Ti implants, which would ultimately contribute to the improved long-term success of Ti implants.
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Hematological neoplasms are heterogeneous diseases with various subtypes, each with its unique genomic features. Cell culture and slide preparation are essential steps to enrich and collect sufficient neoplastic cells for cytogenetic studies of the neoplasms. This chapter describes methods that are commonly used for culturing hematological neoplastic cells and preparing cytogenetic slides for clinical diagnosis and research of the neoplasms.
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Análisis Citogenético , Neoplasias Hematológicas , Humanos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patología , Análisis Citogenético/métodos , Técnicas de Cultivo de Célula/métodosRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease that requires personalized clinical treatment. Assigning patients to different risk categories and cytogenetic abnormality and genetic mutation groups has been widely applied for prognostic stratification of DLBCL. Increasing evidence has demonstrated that dysregulated metabolic processes contribute to the initiation and progression of DLBCL. Metabolic competition within the tumor microenvironment is also known to influence immune cell metabolism. However, metabolism- and immune-related stratification has not been established. Here, 1660 genes involved in 84 metabolic pathways were selected and tested to establish metabolic clusters (MECs) of DLBCL. MECs established based on independent lymphoma datasets distinguished different survival outcomes. The CIBERSORT algorithm and EcoTyper were applied to quantify the relative abundance of immune cell types and identify variation in cell states for 13 lineages comprising the tumor micro environment among different MECs, respectively. Functional characterization showed that MECs were an indicator of the immune microenvironment and correlated with distinctive mutational characteristics and oncogenic signaling pathways. The novel immune-related MECs exhibited promising clinical prognostic value and potential for informing DLBCL treatment decisions.
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Linfoma de Células B Grandes Difuso , Redes y Vías Metabólicas , Microambiente Tumoral , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/mortalidad , Humanos , Pronóstico , Biomarcadores de Tumor/metabolismo , Femenino , Masculino , Perfilación de la Expresión Génica , MutaciónRESUMEN
Recurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate the response to therapeutic interventions. CD58 interacts with the CD2 receptor on T cells and NK cells and is recurrently mutated and deleted in DLBCL, suggesting that it may play a role in regulating antitumor immunity. In this study, we comprehensively analyzed the genomic characteristics of CD58 through targeted next-generation sequencing, RNA sequencing (RNA-seq), whole-exome sequencing, and single-cell RNA-seq in patients with newly diagnosed DLBCL. The CD58 mutation rate was 9.1%, and the copy number loss rate was 44.7% among all enrolled patients with DLBCL. Notably, CD58 genetic alterations, along with low CD58 expression, significantly correlated with reduced rates of response to R-CHOP therapy and inferior progression-free survival and overall survival. Single-cell RNA-seq revealed that CD58 expression in tumor cells was negatively correlated with CD8+ T-cell exhaustion/dysfunction status. Insufficient T-cell activation resulting from CD58 alterations could not be attributed solely to CD2 signaling. CD58 inhibited the activity of the JAK2/STAT1 pathway by activating the LYN/CD22/SH2 domain-containing phosphatase 1 (SHP1) axis, thereby limiting PDL1 and IDO expression. Elevated PDL1 and IDO expression in CD58-deficient DLBCL cells led to immune evasion and tumor-intrinsic resistance to chimeric antigen receptor T-cell therapy. Direct activation of CD58-CD2 costimulatory signaling in combination with anti-PDL1 blockade or IDO inhibitor sensitized CD58-deficient DLBCL to chimeric antigen receptor T-cell therapy. Collectively, this work identified the multiple roles of CD58 in regulating antitumor immune responses in DLBCL. Significance: Loss of CD58 mediates immune evasion and therapy resistance in diffuse large B-cell lymphoma by upregulating PDL1 and IDO through LYN/CD22/SHP1 signaling, providing potential targets and therapeutic strategies to improve patient treatment.
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Antígeno B7-H1 , Antígenos CD58 , Indolamina-Pirrol 2,3,-Dioxigenasa , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Antígenos CD58/genética , Antígenos CD58/metabolismo , Femenino , Masculino , Mutación , Animales , Persona de Mediana Edad , Ratones , Línea Celular Tumoral , AncianoAsunto(s)
Células Asesinas Naturales , Linfoma , Humanos , Estudios Retrospectivos , Linfoma/patologíaRESUMEN
Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare extra-nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI-FL and 34 892 nodal FL (N-FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age-adjusted average annual incidence of PGI-FL was 0.111/100000. The median overall survival (OS) for PGI-FL and N-FL patients was 207 and 165 months respectively. The 5-year diffuse large B-cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1-, 5- and 10-year OS and disease-specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI-FL has increased over the past 40 years, and PGI-FL has a better prognosis and a lower DLBCL transformation rate than N-FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high-risk patients and choosing the optimal individualized treatments.
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Neoplasias Gastrointestinales , Linfoma Folicular , Programa de VERF , Humanos , Linfoma Folicular/mortalidad , Linfoma Folicular/epidemiología , Linfoma Folicular/terapia , Linfoma Folicular/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias Gastrointestinales/epidemiología , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/terapia , Adulto , Estudios Retrospectivos , Pronóstico , Anciano de 80 o más Años , Nomogramas , Incidencia , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Adolescente , Adulto JovenRESUMEN
OBJECTIVE: This study was designed to investigate the therapeutic effect of Cangfu Daotan Decoction (CDD) combined with drospirenone and ethinylestradiol tablets (II) on patients with polycystic ovary syndrome (PCOS). METHODS: Patients with PCOS were gathered from September 2020 to September 2022 and divided into the experimental group (n = 36), treated with CDD combined with drospirenone and ethinylestradiol tablets (II), and the control group (n = 41), received only drospirenone and ethinylestradiol tablets (II). Levels of sex hormone, obesity, blood glucose, blood lipid were detected and compared between the two groups pre- and post-treatment. The treatment efficacy, Traditional Chinese Medicine (TCM) syndrome score, adverse drug reactions, and pregnancy rate were compared as well. RESULTS: After treatment, the experimental group had a higher treatment efficacy (94.44% vs 73.17%, P < 0.05) and a higher pregnancy rate (44.44% vs 21.95%, P < 0.05) than the control group, but the difference in the incidence of adverse drug reactions was not statistically significant (P > 0.05). Compared with control group, TCM syndrome score and levels of fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and waist circumference of the experimental group after treatment displayed remarkable reduction (P < 0.05), while the levels of estradiol (E2) and high-density lipoprotein cholesterol (HDL-C) showed a remarkable increase (P < 0.05). CONCLUSION: CDD in combination with drospirenone and ethinylestradiol tablets (II) may be effective in treating PCOS by improving obesity, glucose metabolism and lipid metabolism with no serious adverse events, making it a feasible clinical practice option.
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Androstenos , Medicamentos Herbarios Chinos , Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Embarazo , Femenino , Humanos , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/metabolismo , Obesidad , Comprimidos/uso terapéuticoRESUMEN
BACKGROUND: Infertility is a common reproductive disease that affects not only individuals and families, but also the growth of the social population. Hence, understanding the burden of female infertility in China and worldwide is of great significance for the development of infertility prevention and treatment strategies. METHODS: The Global Burden of Disease Study (GBD 2019) Data Resources were used to collect and collate relevant data on female infertility in China and worldwide from 1990 to 2019. The difference in the number, age-standardised prevalence rate (ASPR), disability-adjusted life years and age-standardised disability-adjusted life years rate (ASDR) of women with infertility in different periods and geographical areas were analysed. The autoregressive integrated moving average method was used to predict the ASPR and ASDR of female infertility in China and worldwide in the next 11years. RESULTS: In the past 30years, the number of female infertility cases increased by 7.06million in China and 56.71million worldwide. The corresponding average annual increase of ASPR was 10.10% and 7.28%, respectively, and that of ASDR was 0.08% and 0.79%, respectively. In addition, there are differences in age and time between Chinese and global female infertility. In 1990, the crude prevalence rate of female infertility was the highest in women aged 40-44years and 35-39years in China and worldwide, respectively. In 2019, the crude prevalence rate of female infertility was still the highest in women aged 40-44years in China, whereas that around the world reached the highest in women aged 30-34years, which was significantly earlier. The forecast for the next 11years suggests that the ASPR and ASDR for female infertility in China will first rise and then decline, but the overall magnitude of change is not very significant, whereas the ASPR and ASDR for female infertility globally are still on the rise. The ASPR value of female infertility is expected to be 5025.56 in 100 000 persons in China and 3725.51 in 100 000 persons worldwide by 2030. The ASDR value of female infertility is expected to be 26.16 in 100 000 persons in China and 19.96 in 100 000 persons worldwide by 2030. CONCLUSION: The burden of female infertility is still increasing in China and worldwide. Therefore, it is of great significance to pay more attention to infertile women, and advocate a healthy lifestyle to reduce the burden of disease for infertile women.
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Infertilidad Femenina , Humanos , Femenino , Infertilidad Femenina/epidemiología , Factores de Riesgo , Prevalencia , China/epidemiología , Predicción , Salud GlobalRESUMEN
ETV6::ABL1 gene fusion is a rare recurrent genomic rearrangement associated with hematologic malignancies, and frequently occurs with additional anomalies. Due to the opposite chromosome orientations of the ETV6 and ABL1 genes, an oncogenic in-frame ETV6::ABL1 gene fusion cannot be formed by a simple translocation. The molecular mechanism of the ETV6::ABL1 fusion and the significance of co-occurring anomalies are not fully understood. We characterized genomic alterations in an individual with ETV6::ABL1 gene-fusion-positive myeloid neoplasm using various genomic technologies. Our findings uncovered a molecular mechanism of the ETV6::ABL1 fusion, in which a paracentric inversion within the short arm of chromosome 12 (12p) and a translocation between the long arm of a chromosome 9 and the 12p with the inversion were involved. In addition, we detected multiple additional anomalies in the individual, and our findings suggested that the ETV6::ABL1 fusion occurred as a secondary event in a subset of cells with the additional anomalies. We speculate that the additional anomalies may predispose to further pathogenic changes, including ETV6::ABL1 fusion, leading to neoplastic transformation.
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Trastornos Mieloproliferativos , Neoplasias , Humanos , Translocación Genética/genética , Trastornos Mieloproliferativos/genética , Fusión Génica , Genómica , Neoplasias/genéticaRESUMEN
Fluorescent RNAs, aptamers that bind and activate small fluorogenic dyes, have provided a particularly attractive approach to visualizing RNAs in live cells. However, the simultaneous imaging of multiple RNAs remains challenging due to a lack of bright and stable fluorescent RNAs with bio-orthogonality and suitable spectral properties. Here, we develop the Clivias, a series of small, monomeric and stable orange-to-red fluorescent RNAs with large Stokes shifts of up to 108 nm, enabling the simple and robust imaging of RNA with minimal perturbation of the target RNA's localization and functionality. In combination with Pepper fluorescent RNAs, the Clivias enable the single-excitation two-emission dual-color imaging of cellular RNAs and genomic loci. Clivias can also be used to detect RNA-protein interactions by bioluminescent imaging both in live cells and in vivo. We believe that these large Stokes shift fluorescent RNAs will be useful tools for the tracking and quantification of multiple RNAs in diverse biological processes.
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Aptámeros de Nucleótidos , Colorantes Fluorescentes , ARN , Microscopía Fluorescente , Aptámeros de Nucleótidos/genéticaRESUMEN
Perinatal hypoxia-ischemia (HI) insult is an important cause of neonatal encephalopathy, and the effective therapeutic approaches are currently limited. Interleukin (IL)-33 acts as a member of the IL-1 superfamily and has been shown to be neuroprotective following experimental neonatal HI and adult stroke. Here, we explore the effect of IL-33 and its specific receptor ST2 axis on endogenous neurogenesis in neonatal brain after HI. ST2 was found on the surface of NSCs, and the expression of ST2 was further enhanced after HI challenge. Delivery of IL-33 obviously repopulated the size of NSC pool, whereas ST2 deficiency worsened the neurogenesis of NSCs in neonatal brain post HI insult. Further in vivo and in vitro studies showed IL-33 regulates the survival, proliferation and differentiation of NSCs through ST2 signaling pathways. Intriguingly, IL-33 facilitated translocation of Nrf2 from the cytoplasm to the nucleus, which is involved in neural differentiation of NSCs. These data demonstrate a critical role of IL-33/ST2 axis in regulation of endogenous neurogenesis of NSCs via activation of the Nrf2 signaling, which provide a new insight into the effect of IL-33 in neonatal brain following HI injury.
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Hipoxia-Isquemia Encefálica , Células-Madre Neurales , Recién Nacido , Humanos , Animales , Interleucina-33/metabolismo , Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Neurogénesis , Isquemia/metabolismo , Hipoxia-Isquemia Encefálica/terapia , Hipoxia-Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Animales Recién NacidosRESUMEN
Follicular lymphoma (FL), the most common indolent lymphoma, is a clinically and genetically heterogeneous disease. However, the prognostic value of driver gene mutations and copy number alterations has not been systematically assessed. Here, we analysed the clinical-biological features of 415 FL patients to identify variables associated with disease progression within 24 months of first-line therapy (POD24). Patients with B symptoms, elevated lactate dehydrogenase and ß2-microglobulin levels, unfavourable baseline haemoglobin levels, advanced stage, and high-risk FL International Prognostic Index (FLIPI) scores had an increased risk of POD24, with FLIPI being the most important factor in logistic regression. HIST1H1D, identified as a driver mutation, was correlated with POD24. Gains of 6p22.2 (HIST1H1D) and 18q21.33 (BCL2) and loss of 1p36.13 (NBPF1) predicted POD24 independent of FLIPI. Gene expression profiling of FL samples showed that the POD24 cohort was significantly enriched in the inflammatory response (mediated by interferon and tumour necrosis factor), cell cycle regulation (transcription, replication and proliferation) sets and PI3K-AKT-mTOR signalling. This result was further validated with transcriptome-wide information provided by RNA-seq at single-cell resolution. Our study, performed on a large cohort of FL patients, highlights the importance of distinctive genetic alterations and gene expression relevant to disease diagnosis and early progression.
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Linfoma Folicular , Humanos , Linfoma Folicular/terapia , Transcriptoma , Fosfatidilinositol 3-Quinasas/genética , Pronóstico , Mutación , Perfilación de la Expresión Génica , GenómicaRESUMEN
OX40 enhances the T-cell activation via costimulatory signaling. However, its molecular characteristics and value in predicting response to immunochemotherapy in DLBCL remain largely unexplored. Here, we performed an integrative analysis of sequencing and multiplex immunofluorescence staining, and discovered abnormally higher expression of OX40 in DLBCL patients. Elevated OX40 could activate T cells leading to a higher immune score for tumor immune microenvironment (TiME). OX40 upregulation simultaneously happened with immune-related genes including PD-1, CTLA4 and TIGIT et,al. Patients with high OX40 expression exhibited a lower Ann Arbor stage and IPI score and more easily achieved a complete response/partial response. The analysis of infiltrated T-cell subset revealed that patients with a greater number of CD4+/OX40+ or CD8+/OX40+ T cells had a longer OS. Our findings indicated that OX40 shapes an inflamed tumor immune microenvironment and predicts response to immunochemotherapy, providing insights for the application of OX40 agonist in DLBCL patients.
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Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Linfocitos T CD8-positivos , Subgrupos de Linfocitos T/patología , Transducción de Señal , Microambiente Tumoral , PronósticoRESUMEN
Soft-tissue integration (STI) plays an essential role in the long-term success of percutaneous Ti implants since it acts as a biological barrier that protects the soft and hard tissue around implants. Surface modification of Ti implants with drug-release properties to achieve soft-tissue regeneration has been proven to be effective in STI. However, the short-acting effect caused by the uncontrolled drug release of the topical delivery system limits long-term STI enhancement. Herein, a long-acting protein delivery system for Ti implants that involved micro-arc oxidation of Ti surfaces (MAO-Ti) and localized immobilization of cellular communication network factor 2 (CCN2) bearing mesoporous silica nanoparticles (MSNs) on MAO-Ti was prepared, namely, CCN2@MSNs-Ti. The CCN2 release study of CCN2@MSNs-Ti demonstrated a sustained-release profile for 21 days, which was able to maintain long-term stable STI. In addition, in vitro cell behavior evaluation results indicated that CCN2@MSNs-Ti could promote the STI-related biological response of human dermal fibroblasts via the FAK-MAPK pathway. More importantly, the system could effectively enhance STI after 4 weeks and proinflammatory factors in the soft tissue decreased significantly in a rat model of implantation. These results denote that CCN2@MSNs-Ti showed an appealing application prospect for enhanced STI around transcutaneous Ti implants, which would ultimately result in an increased success rate of percutaneous Ti implants.
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Prótesis e Implantes , Titanio , Ratas , Humanos , Animales , Titanio/farmacología , Oxidación-Reducción , Propiedades de SuperficieRESUMEN
Non-invasive prenatal screening (NIPS) is a DNA sequencing-based screening test for fetal aneuploidies and possibly other pathogenic genomic abnormalities, such as large deletions and duplications. Validation and quality assurance (QA) of this clinical test using plasmas with and without targeted chromosomal abnormalities from pregnant women as negative and positive controls are required. However, the positive plasma controls may not be available for many laboratories that are planning to establish NIPS. Limited synthetic positive plasmas are commercially available, but the types of abnormalities and the number/quantity of synthetic plasmas for each abnormality are insufficient to meet the minimal requirements for the initial validation. We report here a method of making synthetic positive plasmas by adding cell-free DNA (cfDNA) isolated from culture media of prenatal cells with chromosomal abnormalities to the plasmas from non-pregnant women. Thirty-eight positive plasmas with various chromosomal abnormalities, including autosomal and sex chromosomal aneuploidies, large deletions and duplications, were synthesized. The synthetic plasmas were characterized side-by-side with real positive plasmas from pregnant women and commercially available synthetic positive plasmas using the Illumina VeriSeq NIPT v2 system. All chromosomal abnormalities in the synthetic plasmas were correctly identified with the same testing sensitivity and specificity as in the real and commercial synthetic plasmas. The findings demonstrate that the synthetic positive plasmas are excellent alternatives of real positive plasmas for validation and QA of NIPS. The method described here is simple and straightforward, and can be readily used in clinical genetics laboratories with accessibility to prenatal cultures.
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Identifying the key factors mediating the progression from hypertension to cardiac hypertrophy is critically important for developing a strategy to protect against heart failure. Serum exosomes have been revealed to be involved in the development of cardiovascular disease. In the current study, we found that either serum or serum exosomes derived from SHR induced hypertrophy in H9c2 cardiomyocytes. SHR Exo injection through the tail vein for 8 weeks induced left ventricular wall thickening and decreased cardiac function in C57BL/6 mice. SHR Exo carried the renin-angiotensin system (RAS) proteins AGT, renin, and ACE into cardiomyocytes, which increased the autocrine secretion of Ang II. Moreover, the AT1-type receptor antagonist telmisartan prevented hypertrophy of H9c2 cells induced by SHR Exo.These results identified a novel role of exosomes derived from SHR serum in cardiac hypertrophy and revealed that SHR Exo induced cardiac hypertrophy by carrying AGT, renin, and ACE proteins into cardiomyocytes to increase their autocrine secretion of Ang II. The emergence of this new mechanism will help us better understand how hypertension progresses to cardiac hypertrophy.
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Exosomas , Hipertensión , Ratas , Ratones , Animales , Angiotensina II/metabolismo , Ratas Endogámicas SHR , Miocitos Cardíacos/metabolismo , Renina/metabolismo , Exosomas/metabolismo , Ratones Endogámicos C57BL , Cardiomegalia/inducido químicamente , Cardiomegalia/metabolismo , Sistema Renina-Angiotensina , Hipertensión/metabolismoRESUMEN
Rice-duck and rice-crayfish co-culture patterns can increase soil productivity and sustainability and reduce the use of chemical pesticides and fertilizers, thereby reducing the resulting negative environmental impacts. However, most studies have focused on the rice-duck and rice-crayfish binary patterns and have ignored integrated systems (three or more), which may have unexpected synergistic effects. To test these effects, a paddy field experiment was carried out in the Chaohu Lake Basin, Hefei city, Southeast China. Four groups, including a rice-duck-crayfish ecological co-culture system (RDC), idle field (CK), single-season rice planting system (SSR), and double-season rice planting system (DSR), were established in this study. The results showed that the RDC improved the soil physical properties, fertility, humus content, and enzyme activity. In the RDC system, the soil total nitrogen content ranged from 8.54% to 28.37% higher than other systems in the 0-10 cm soil layer. Similar increases were found for soil total phosphorus (8.22-30.53%), available nitrogen (6.93-22.72%), organic matter (18.24-41.54%), urease activity (16.67-71.51%), and acid phosphatase activity (23.41-66.20%). Relative to the SSR treatment, the RDC treatment reduced the total losses of nitrogen and phosphorus runoff by 24.30% and 10.29%, respectively. The RDC also did not cause any harm to the soil in terms of heavy metal pollution. Furthermore, the RDC improved the yield and quality of rice, farmer incomes, and eco-environmental profits. In general, the RDC can serve as a valuable method for the management of agricultural nonpoint-source pollution in the Chaohu Lake area and the revitalization of the countryside.