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The potential of enhanced agricultural management practices to drive sustainability is rarely quantified at grassroots level. Here we analyse nitrogen use and loss in Chinese cropland, drawing from data collected in 2,238,550 sites in two national agricultural pollution source censuses from 2007 to 2017. We find an upswing of 10% in crop yields and an 8% reduction in nitrogen pollution during this period, owing to the promotion and adoption of various management practices (including the combination of organic and chemical fertilizers, straw recycling and deep placement of fertilizer). These practices have collectively contributed to an 18% increase in nitrogen use efficiency in the country. By fully embracing them, we project that annual cropland pollution could be further reduced by up to 1.4 Mt of nitrogen without compromising crop yields. Environmental and human health benefits are projected to consistently outweigh implementation costs in the future, with total benefits reaching US$15 billion.
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Agricultura , Fertilizantes , Nitrógeno , China , Humanos , Agricultura/métodos , Fertilizantes/análisis , Conservación de los Recursos Naturales/métodos , Productos Agrícolas , Contaminación Ambiental/prevención & control , Desarrollo SostenibleRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: To explore the differences in the anti-inflammatory efficacy and mechanisms of the Miao medicine, both raw and after processing, using the "sweat soaking method" of Radix Wikstroemia indica (RWI). AIM OF THE STUDY: The purpose of this study was to explore the differences in the anti-inflammatory efficacy and mechanism of action before and after the processing of the Miao medicine (RWI) using the "sweat soaking method." MATERIALS AND METHODS: Network pharmacology technology was used to construct the "drug-component target-pathway-disease" network, and the main anti-inflammatory pathways of RWI were identified. Rat models of collagen-induced arthritis were established. The changes in body weight, swelling rate of the foot pad and ankle joint, arthritis index, thymus index, spleen index, pathological changes of the ankle joint, and the content of inflammatory cytokines (IL-1ß, IL-2, IL-6, IL-10, TNF-α, and NO) were used as indices to evaluate the effect of RWI on rats with collagen-induced arthritis before and after its processing. Plasma and urine samples were collected from the rats, and the potential biomarkers of, and metabolic pathways underlying the anti-inflammatory effects of RWI before and after processing were identified using 1H-Nuclear magnetic resonance metabolomics combined with a multivariate statistical analysis. RESULTS: Eleven key anti-inflammatory targets of IL6, IL-1ß, TNF, ALB, AKT1, IFNG, INS, STAT3, EGFR, TP53, and SRC were identified by network pharmacology. The PI3K-Akt signaling pathway, steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, tryptophan metabolism, and other pathways were mainly involved in these effects. Pharmacodynamic studies found that both raw and processed RWI products downregulated inflammatory factors in rats with collagen-induced arthritis and alleviated the pathological changes. A total of 41 potential pathways for the anti-inflammatory effects of raw RWI products and 36 potential pathways for the anti-inflammatory effects of processed RWI products were identified by plasma and urine metabolomics. The common pathways of network pharmacology and metabolomics were steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. CONCLUSIONS: The anti-inflammatory effect of RWI was mainly related to the regulation of steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. Finally, the "sweat soaking method" enhanced the anti-inflammatory effect of RWI.
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Artritis Experimental , Medicamentos Herbarios Chinos , Wikstroemia , Ratas , Animales , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Sudor/química , Fosfatidilinositol 3-Quinasas , Triptófano , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/análisis , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Arginina , Esteroides , Hormonas , ProlinaRESUMEN
Objective: The objective of this study is to assess the clinical performance of a urine-based high-risk human papillomavirus (hrHPV) test for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). Methods: Between September and December 2021, women aged 20 to 65 years referred to colposcopy clinic were prospectively recruited at three clinical centers in China. Paired urine and cervical specimens from all enrolled women were obtained for hrHPV DNA fluorescence quantitative PCR test. The results of liquid-based cytology (LBC), colposcopy and diagnostic biopsies were collected. We evaluated the sensitivity and specificity for CIN and assessed the agreement/kappa value. Results: A total of 732 women (median age, 40 years) with valid results were included in the study, and 130 (17.8%) women were histologically confirmed as CIN2+. The sensitivity of urine and cervical test for CIN2+ and CIN3+ were 87.69% and 85.45%, respectively. The specificity of urine test performed better than cervical test in women with
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OBJECTIVE: Diminished ovarian reserve (DOR) can lead to early menopause, poor fecundity, and an increased risk of disorders such as osteoporosis, cardiovascular disease, and cognitive impairment, seriously affecting the physical and mental health of women. There is still no safe and effective strategy or method to combat DOR. We have developed a novel Chinese herbal formula, Tongji anti-ovarian aging 101 (TJAOA101), to treat DOR. However, its safety and efficacy need to be further validated. METHODS: In this prospective and pre-post clinical trial, 100 eligible patients aged 18-45 diagnosed with DOR will be recruited. All participants receive TJAOA101 twice a day for 3 months. Then, comparisons before and after treatment will be analyzed, and the outcomes, including anti-mullerian hormone (AMH) and follicle-stimulating hormone (FSH) levels and the antral follicle count (AFC), the recovery rate of menopause, and the Kupperman index (KMI), will be assessed at baseline, every month during medication (the intervention period), and 1, 3 months after medication (the follow-up period). Assessments for adverse events will be performed during the intervention and follow-up periods. CONCLUSION: A multicenter, prospective study will be conducted to further confirm the safety and efficacy of TJAOA101 in treating DOR and to provide new therapeutic strategies for improving the quality of life in DOR patients.
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Enfermedades del Ovario , Reserva Ovárica , Femenino , Humanos , Estudios Prospectivos , Calidad de Vida , Envejecimiento , Estudios Multicéntricos como AsuntoRESUMEN
Maintaining food production while reducing agricultural nitrogen pollution is a grand challenge under global climate change. Yet, the response of global agricultural nitrogen uses and losses to climate change on the temporal and spatial scales has not been fully characterized. Here, using historical data for 1961-2018 from over 150 countries, we show that global warming leads to small temporal but substantial spatial impacts on cropland nitrogen use and losses. Yield and nitrogen use efficiency increase in 29% and 56% of countries, respectively, whereas they reduce in the remaining countries compared with the situation without global warming in 2018. Precipitation and farm size changes would further intensify the spatial variations of nitrogen use and losses globally, but managing farm size could increase the global cropland nitrogen use efficiency to over 70% by 2100. Our results reveal the importance of reducing global inequalities of agricultural nitrogen use and losses to sustain global agriculture production and reduce agricultural pollution.
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Cambio Climático , Nitrógeno , Agricultura/métodos , Calentamiento Global , Productos AgrícolasRESUMEN
Rapid demographic ageing substantially affects socioeconomic development1-4 and presents considerable challenges for food security and agricultural sustainability5-8, which have so far not been well understood. Here, by using data from more than 15,000 rural households with crops but no livestock across China, we show that rural population ageing reduced farm size by 4% through transferring cropland ownership and land abandonment (approximately 4 million hectares) in 2019, taking the population age structure in 1990 as a benchmark. These changes led to a reduction of agricultural inputs, including chemical fertilizers, manure and machinery, which decreased agricultural output and labour productivity by 5% and 4%, respectively, further lowering farmers' income by 15%. Meanwhile, fertilizer loss increased by 3%, resulting in higher pollutant emissions to the environment. In new farming models, such as cooperative farming, farms tend to be larger and operated by younger farmers, who have a higher average education level, hence improving agricultural management. By encouraging the transition to new farming models, the negative consequences of ageing can be reversed. Agricultural input, farm size and farmer's income would grow by approximately 14%, 20% and 26%, respectively, and fertilizer loss would reduce by 4% in 2100 compared with that in 2020. This suggests that management of rural ageing will contribute to a comprehensive transformation of smallholder farming to sustainable agriculture in China.
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Distribución por Edad , Agricultura , Agricultores , Granjas , Seguridad Alimentaria , Población Rural , Desarrollo Sostenible , Humanos , Agricultura/economía , Agricultura/educación , Agricultura/métodos , Agricultura/organización & administración , China , Agricultores/educación , Agricultores/estadística & datos numéricos , Granjas/economía , Granjas/organización & administración , Granjas/estadística & datos numéricos , Granjas/tendencias , Fertilizantes/análisis , Factores de Edad , Seguridad Alimentaria/economía , Seguridad Alimentaria/métodos , Desarrollo Sostenible/economía , Desarrollo Sostenible/tendencias , Población Rural/estadística & datos numéricos , Población Rural/tendencias , Eficiencia , Contaminantes AmbientalesRESUMEN
Dysregulated endocrine hormones (EHs) contribute to tumorigenesis, but how EHs affect the tumor immune microenvironment (TIM) and the immunotherapy of non-small cell lung cancer (NSCLC) is still unclear. Here, endogenous ouabain (EO), an adrenergic hormone, is elevated in patients with NSCLC and closely related to tumor pathological stage, metastasis, and survival. EO promotes the suppression of TIM in vivo by modulating the expression of immune checkpoint proteins, in which programmed cell death protein ligand 1 (PD-L1) plays a major role. EO increases PD-L1 transcription; however, the EO receptor Na- and K-dependent adenosine triphosphatase (Na, K-ATPase) α1 interacts with PD-L1 to trigger the endocytic degradation of PD-L1. This seemingly contradictory result led us to discover the mechanism whereby EO cooperates with Na, K-ATPase α1 to finely control PD-L1 expression and dampen tumoral immunity. In conclusion, the Na, K-ATPase α1/EO signaling facilitates immune escape in lung cancer, and manipulation of this signaling shows great promise in improving immunotherapy for lung adenocarcinoma.
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Adenocarcinoma del Pulmón , Antígeno B7-H1 , Neoplasias Pulmonares , ATPasa Intercambiadora de Sodio-Potasio , Humanos , Adenosina Trifosfatasas , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Ligandos , Pulmón/metabolismo , Neoplasias Pulmonares/patología , Microambiente Tumoral , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
Cropland is a main source of global nitrogen pollution1,2. Mitigating nitrogen pollution from global croplands is a grand challenge because of the nature of non-point-source pollution from millions of farms and the constraints to implementing pollution-reduction measures, such as lack of financial resources and limited nitrogen-management knowledge of farmers3. Here we synthesize 1,521 field observations worldwide and identify 11 key measures that can reduce nitrogen losses from croplands to air and water by 30-70%, while increasing crop yield and nitrogen use efficiency (NUE) by 10-30% and 10-80%, respectively. Overall, adoption of this package of measures on global croplands would allow the production of 17 ± 3 Tg (1012 g) more crop nitrogen (20% increase) with 22 ± 4 Tg less nitrogen fertilizer used (21% reduction) and 26 ± 5 Tg less nitrogen pollution (32% reduction) to the environment for the considered base year of 2015. These changes could gain a global societal benefit of 476 ± 123 billion US dollars (USD) for food supply, human health, ecosystems and climate, with net mitigation costs of only 19 ± 5 billion USD, of which 15 ± 4 billion USD fertilizer saving offsets 44% of the gross mitigation cost. To mitigate nitrogen pollution from croplands in the future, innovative policies such as a nitrogen credit system (NCS) could be implemented to select, incentivize and, where necessary, subsidize the adoption of these measures.
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Producción de Cultivos , Productos Agrícolas , Contaminación Ambiental , Nitrógeno , Suelo , Humanos , Análisis Costo-Beneficio , Ecosistema , Fertilizantes/análisis , Nitrógeno/análisis , Suelo/química , Contaminación Ambiental/economía , Contaminación Ambiental/prevención & control , Producción de Cultivos/economía , Producción de Cultivos/métodos , Producción de Cultivos/tendenciasRESUMEN
In brief: Inflammation and abnormal immune response are the key processes in the development of endometriosis (EMs), and m6A modification can regulate the inflammatory response. This study reveals that METTL3-mediated N6-methyladenosine (m6A) modification plays an important role in EMs. Abstract: m6A modification is largely involved in the development of different diseases. This study intended to investigate the implication of m6A methylation transferase methyltransferase like 3 (METTL3) in EMs. EMs- and m6A-related mRNAs and long non-coding RNAs were identified through bioinformatics analysis. Next, EM mouse models established by endometrial autotransplantation and mouse endometrial stromal cell (mESC) were prepared and treated with oe-METTL3 or sh-MIR17HG for pinpointing the in vitro and in vivo effects of METTL3 on EMs in relation to MIR17HG through the determination of mESC biological processes as well as estradiol (E2) and related lipoprotein levels. We demonstrated that METTL3 and MIR17HG were downregulated in the EMs mouse model. Overexpression of METTL3 suppressed the proliferation, migration, and invasion of mESCs. In addition, METTL3 enhanced the expression of MIR17HG through m6A modification. Moreover, METTL3 could inhibit the E2 level and alter related lipoprotein levels in EMs mice through the upregulation of MIR17HG. The present study highlighted that the m6A methylation transferase METTL3 prevents EMs progression by upregulating MIR17HG expression.
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Endometriosis , Metiltransferasas , Humanos , Femenino , Ratones , Animales , Metiltransferasas/genética , Metiltransferasas/metabolismo , Empalme Alternativo , Endometriosis/genética , Metilación , Regulación hacia ArribaRESUMEN
Nitrogen use efficiency (NUE, defined as the fraction of N input harvested as product) is an important indicator to understand nitrogen use and losses in croplands as an element of determining sustainable food production. China, as the country with the largest amount of nitrogen fertilizer use globally, research into NUE consistently finds it to be much lower than that in developed countries. Understanding the driving forces of the underlying causes of this low NUE is thus crucial to improve nitrogen use and reduce losses in China. Here we applied the CHANS model to estimate cropland NUE for over 2800 counties in China for the year 2017. Results showed that in most counties NUE ranged between 20% and 40%, while an NUE >50% was mainly found in Northeastern China, likely as a result of large-scale, modern agriculture operations. The source of N input and crop types significantly affected NUE in our assessment. Nitrogen deposition, straw recycling, and biological nitrogen fixation (BNF) could improve NUE, while chemical nitrogen fertilizer and manure inputs reduce NUE. Grain crops have a much higher NUE compared to vegetables, which are often over-fertilized. Moreover, NUE in Southern China is strongly influenced by natural factors such as temperature and precipitation. Specifically, NUE in the Yangtze River Delta (eastern coastal region of China) is associated with socio-economic factors including GDP and the degree of urbanization, while in North-central China, NUE is mainly determined by nitrogen input sources. These examples illustrate that approaches aiming at improving NUE need to be location-specific with consideration of multiple natural and socioeconomic factors.
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Fertilizantes , Nitrógeno , Nitrógeno/análisis , Agricultura/métodos , Productos Agrícolas , Estiércol , ChinaRESUMEN
Erythropoietin-producing hepatoma receptor A2 (EphA2), receptor tyrosine kinase, the most widespread member of the largest receptor tyrosine kinase family, plays a critical role in physiological and pathological conditions. In recent years, the role of EphA2 in the occurrence and development of cancer has become a research hotspot and is considered a promising potential target. Our previous studies have shown that EphA2 has an indisputable cancer-promoting role in cervical cancer, but its related mechanism requires further research. In this study, high-throughput sequencing was performed on EphA2 knockdown cervical cancer cells and the control group. An analysis of differentially expressed genes revealed that EphA2 may exert its cancer-promoting effect through C-X-C motif chemokine ligand 11 (CXCL11). In addition, we found that EphA2 could further regulate programmed cell death ligand 1 (PD-L1) through CXCL11. This has also been further demonstrated in in vivo experiments. Our study demonstrated that EphA2 plays a tumor-promoting role in cervical carcinoma through the CXCL11/PD-L1 pathway, providing new guidance for the targeted therapy and combination therapy of cervical carcinoma.
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Objective: To evaluate the optimal waiting period for frozen-thawed embryo transfer (FET) after hysteroscopic polypectomy (HSC-P). Design: Retrospective cohort. Setting: University-affiliated hospital. Patients: All patients included in this research underwent hysteroscopy before the first FET cycle after whole embryo freezing. A total of 206 patients had undergone HSC-P, and 3681 patients without endometrial polyps were defined as the controls. Interventions: HSC-P. Main outcome measures: The HSC-P group was divided into three subgroups based on the time interval between HSC-P and the start of an FET cycle. Subgroup 1 consisted of patients who underwent FET after their next menses, subgroup 2 after two menstrual cycles, and subgroup 3 after three or more menstrual cycles. Demographics, baseline in vitro fertilization (IVF) characteristics, and pregnancy outcomes, especially perinatal outcomes after FET were compared among the groups. Results: There were 137 patients in subgroup 1, 40 in subgroup 2, and 29 in subgroup 3. There were no differences in the baseline characteristics of the three groups. IVF-related data and FET-related data, such as endometrial thickness and ET no. Of embryoes, were similar among the three subgroups. The three subgroups showed no significant differences in implantation rate, biochemical pregnancy rate, abortion rate, clinical pregnancy rate or live birth rate. Besides, There was no significant difference in perinatal outcomes including very preterm delivery, preterm delivery, low birth weight, macrosomia, small for gestational age, large for gestational age, birth weight(g), birth-height(cm)and Apgar Scores. Conclusions: Compared with FET after their next menses, FET after two or more menstrual cycles after HSC-P does not necessarily produce superior outcomes.
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Nacimiento Prematuro , Transferencia de Embrión , Femenino , Humanos , Recién Nacido , Embarazo , Índice de Embarazo , Puntaje de Propensión , Estudios RetrospectivosRESUMEN
Multiple studies have proved that participating in sports can effectively reduce adults' depression. This paper provides evidence from China by using the survey data from China Family Panel Studies (CFPS), which contains sport-types, personal characteristics, and CES-D20 depression-scale score data of 33,236 individuals. In addition to the Ordinary Least Squares regression model, we adopt the Two-way Fixed Effect and Propensity Score Matching method to alleviate the endogeneity. The empirical result shows that for every additional time of physical exercise, the depression level drops by an average of 0.152; the depression level of people who participate in sports is significantly lower than that of non-participants by 0.397 points. The lowering effect of physical activity on depression is not linear, and excessive exercise may lead to increased depression. Furthermore, heterogeneity analyses discover that with the increase of age and education, the impact continued to expand. For every increase in physical exercise of the group over 76-year old, the depression level decreased by 0.373 points; while for individuals with primary school education, their depression level decreased only by 0.124 points.
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Ejercicio Físico , Deportes , Anciano , Antidepresivos , China , Escolaridad , HumanosRESUMEN
Radix Wikstroemia indica (L.) C.A. Mey. (RWI) is a toxic medicinal species primarily present in the Miao area of China. The toxicity of RWI is effectively reduced whilst maintaining the therapeutic effect when processed using the 'sweat-soaking method', which is a common method of Traditional Chinese Medicine preparation. However, there is a lack of scientific and medical evidence to explain the potential mechanisms by which the toxicity of RWI is reduced after preparation using this method, and the endogenous systemic metabolic effect of RWI remains uncertain. The aim of the present study was to explore the endogetnous metabolic alterations caused by RWI and to examine the possibility of reducing the toxicity of RWI using the sweat-soaking method using proton nuclear magnetic resonance (NMR) metabolomic analysis in rats. Principal Component Analysis, Partial Least Squares-Discriminant Analysis (PLS-DA) and Orthogonal PLS-DA were used to assess individual proton NMR spectra. A total of 34 metabolic products were altered after delivering raw RWI, and 32 endogenous metabolites were induced by processed RWI. The metabolic pathways that lead to a significant impact on energy and carbohydrate, amino acid, organic acids and lipid metabolism following raw and processed RWI use were identified. The mitochondria of hepatic and renal tubules of rats were injured in the raw RWI group, whereas the processed product reduced or interfered with energy substrate, carbohydrate and amino acid metabolism, whilst reducing the levels of metabolic markers of hepatotoxicity and nephrotoxicity, without causing damage to the mitochondria. Our previous study showed that the median lethal dose (LD50) value of raw RWI was 4.05 g/kg in rats after oral administration; however, the LD50 value of the processed RWI could not be measured. The maximum tolerated dose and minimum lethal dose were 20 and 30 g/kg for the processed RWI, respectively, corresponding to 109 and 164 times the clinical daily dose (0.029 g/kg). Thus, the sweat-soaking method reduced the toxicity of RWI. Moreover, after processing, the toxic component YH-10 was converted into a YH-10 + OH compound, reducing the content of the toxic YH-10 by 48%, whilst also reducing the contents of the toxic components YH-12 and YH-15 by 44 and 65%, respectively. In conclusion, the present study showed that the sweat-soaking method reduced the toxicity of RWI, as evidenced by the reduction of the levels of metabolic markers and the activity of metabolic pathways, thus providing a basis for processing of RWI for clinical use.
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Farm size affects nitrogen fertilizer input and agricultural practices, which are key determinants of ammonia (NH3) emissions from croplands. However, the degree to which NH3 emissions are associated with changes in farm size is not well understood yet despite its crucial role in achieving agricultural sustainability in China, where agricultural production is still dominated by smallholder farms. Here we provide a first analysis of the relationship between farm size and NH3 emissions based on 863â¯000 surveys conducted in 2017 across China. Results show that NH3 emissions (kg ha-1) on average decrease by 0.07% for each 1% increase in average farm size. This change occurs mainly due to a reduction in nitrogen fertilizer use and the introduction of more efficient fertilization practices. The largest reduction in NH3 emissions is found in maize, with less pronounced changes in rice cultivation, and none for wheat production. Overall lower NH3 emissions factors can be observed in the north of China with increasing farm size, especially in the northeast, the opposite pattern was found in the south. National total NH3 emissions could be approximately halved (1.5 Tg) in a scenario favoring a conversion to large-scale farming systems. This substantial reduction potential highlights the potential of such a transition to reduce NH3 emissions, including benefits from a socioeconomic point of view as well as for improving air quality.
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Amoníaco , Fertilizantes , Agricultura , China , Productos Agrícolas , Granjas , Nitrógeno/análisisRESUMEN
EMs is a kind of benign disease with certain malignant behaviors. The adhesion, invasive growth, and angiogenesis of ectopic endometrial cells are the pathological basis of EMs occurrence, but its etiology and pathogenesis have not been completely illustrated yet. In our research, we aim to investigate the role of miR-363 in the pathogenesis of endometriosis. Real-time quantitative PCR was used to detect the expression of miR-363 before and after ESC/NSC transfection. CCK-8, flow cytometry, and transwell assay were used to detect the effect of the miR-363 expression on cell proliferation, apoptosis, and invasion. The effects of the miR-363 expression on the contents of Fas/APO-1 and ICAM-1 in cell culture supernatant were detected by ELISA. qRT-PCR and WB assay were used to detect the effects of the miR-363 expression on the mRNA and protein expression levels of ICAM-1, MMP-7, and VEGF in ESC. The increased expression of miR-363 could inhibit the proliferation and invasion of ESC, promote apoptosis, and inhibit the secretion of FAS/APO-1 and ICAM-1. The knockdown expression of miR-363 promoted proliferation and invasion of NSC, inhibited apoptosis, and promoted secretion of FAS/APO-1 and ICAM-1. VCAM-1, VEGF, and MMP-7 were detected in ESCs before transfection. The protein expression level was higher than that of NSCs. Compared with pretransfection, the protein levels of VCAM-1, VEGF, and MMP-7 in the M-363 group were significantly downregulated. The downregulated expression of miR-363 was associated with a stronger cell proliferation ability, a lower cell apoptosis rate, and a stronger ESC. Migration is associated with invasiveness, proliferation, angiogenesis, and immune escape. The low expression of miR-363 promotes endogenesis through posttranscriptional regulation of target genes VCAM-1, MMP-7, and VEGF. The differential expression of miR-363 between ESC and NSC may be an important factor in the many biological differences between ESC and NSC.
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Endometriosis , Células Epiteliales , MicroARNs , Movimiento Celular/genética , Proliferación Celular/genética , Endometriosis/patología , Endometrio/citología , Endometrio/patología , Células Epiteliales/metabolismo , Femenino , Humanos , MicroARNs/metabolismo , Células del Estroma/patologíaRESUMEN
OBJECTIVES: This retrospective study aimed to investigate the correlations between phenotypes of fetal renal abnormalities on prenatal ultrasound and genetic aetiologies detected using chromosomal microarray analysis (CMA) and whole-exome sequencing (WES). METHODS: Fetuses with renal abnormalities were subjected to CMA and were further analysed by WES when CMA-negative. The detection rates for chromosomal abnormalities and monogenic variants among different types of isolated renal abnormalities and those with extrarenal abnormalities (non-isolated cases) were determined and compared. RESULTS: CMA detected chromosomal abnormalities in 78 of 577 fetuses (13.52%). WES detected monogenic variants in 31 of 160 fetuses (19.38%) that had non-diagnostic CMA results. In cases of isolated hyperechogenic kidney, polycystic kidney disease, and multicystic dysplastic kidney, the detection rates of copy number variants (CNVs) by CMA and monogenic variants by WES were not significantly different (p > 0.05). However, monogenic variants were more frequently detected than CNVs when kidney abnormalities were accompanied by reduced amniotic fluid (p < 0.05). Other renal abnormalities identified on prenatal ultrasound had different detection rates. CONCLUSIONS: Our findings contribute to the overall knowledge of genetic variants associated with prenatally identified renal anomalies and may aid in decision making regarding prenatal genetic testing options for affected pregnancies.
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Variaciones en el Número de Copia de ADN , Diagnóstico Prenatal , Aberraciones Cromosómicas , Femenino , Humanos , Análisis por Micromatrices , Embarazo , Diagnóstico Prenatal/métodos , Estudios Retrospectivos , Ultrasonografía PrenatalRESUMEN
BACKGROUND AND OBJECTIVE: Asparagine synthetase deficiency (ASNSD) is a rare neurometabolic disease caused by variations of the ASNS gene. It manifests as microcephaly, severe developmental delay, and spastic quadriplegia. 71% of ASNSD patients died during early infancy. We aim to investigate mutations related to intractable epilepsy in one Chinese genealogy. MATERIAL AND METHODS: Head Magnetic Resonance Imaging (MRI), whole exome sequencing (WES), and Liquid Chromatography-Mass Spectrometry (LC-MS) to help 2 patients with intractable epilepsy find the underlying mechanisms of disease. RESULTS: These two patients had a compound heterozygous mutation (c.224A > G, p.N75S and c.1612A > G, p.M538V) in the ASNS gene, of which c.1612A > G was a novel mutation. The asparagine levels in patients' plasmas were normal. In addition, they had a later onset, longer survival, and were milder than previously reported ASNSD patients. CONCLUSIONS: Two patients were diagnosed with a milder form of ASNSD. Clinically, the asparagine level in the patient's plasma cannot be used as the only basis to diagnose this disease. This study has expanded the disease phenotype spectrum of ASNSD and broadened the variation profile of the ASNS gene, which can assist in the clinical diagnosis and treatment of ASNSD patients.