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The avermectin derivative doramectin is widely used clinically as an antiparasitic drug and, in addition, doramectin may have a modulatory role in obesity. Adipose tissue macrophage recruitment and polarization play an important role in obesity-induced inflammation and insulin resistance. The aim of this study was to investigate the effects of doramectin on high-fat diet-induced inflammation and macrophage polarization in white adipose tissue of epididymis of obese mice. We found that compared with high-fat diet-fed obese mice, doramectin treatment resulted in a significant decrease in body weight and lipid levels, improved insulin resistance, an increase in the proportion of M2-type macrophages and a decrease in the proportion of M1-type macrophages in the epididymal white adipose tissues, as well as a decrease in the infiltration of inflammatory cells in the adipose tissues. Thus, doramectin can ameliorate high-fat diet-induced obesity and adipose inflammation by affecting macrophage polarization in white adipose tissue.
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LncRNAs have been demonstrated to regulate biological processes in malignant tumors. In our previous study, we identified the immune-related LncRNA RNF144A-AS1 as a potential regulator in SKCM. However, its precise function and regulatory mechanism remain unclear. In this study, we observed upregulation of RNF144A-AS1 in SKCM and found that knockdown of RNF144A-AS1 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition abilities of melanoma cells. Mechanistically, as a high-risk prognostic factor, RNF144A-AS1 regulated biological processes of SKCM by interacting with TAF15 through an RNA-binding protein-dependent (RBP-dependent) manner. Furthermore, we confirmed that TAF15 activated downstream transcriptional regulation of YAP1 to modulate malignant behaviors in melanoma cells. In vivo experiments revealed that knockdown of RNF144A-AS1 inhibited tumorigenic capacity of melanoma cells and exhibited promising therapeutic effects. Collectively, these findings highlight the significance of the RNF144A-AS1/TAF15/YAP1 axis in promoting malignant behaviors in SKCM and provide novel insights into potential prognostic biomarkers and therapeutic targets for this disease.
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Postmenopausal osteoporosis is a common bone metabolic disease, and gut microbiota (GM) imbalance plays an important role in the development of metabolic bone disease. Here, we show that ovariectomized mice had high levels of lipopolysaccharide in serum and gut microbiota dysbiosis through increases in luminal Firmicutes:Bacteroidetes ratio. We depleted the GM through antibiotic treatment and observed improvements in bone mass, bone microstructure, and bone strength in ovariectomized mice. Conversely, transplantation of GM adapted to ovariectomy induced bone loss. However, GM depletion reversed ovariectomy-induced gene expression in the tibia and increased periosteal bone formation. Furthermore, bioinformatics analysis revealed that the G-protein-coupled bile acid receptor (TGR5) and systemic inflammatory factors play key roles in bone metabolism. Silencing TGR5 expression through small interfering RNA (siRNA) in the local tibia and knockout of TGR5 attenuated the effects of GM depletion in ovariectomized mice, confirming these findings. Thus, this study highlights the critical role of the GM in inducing bone loss in ovariectomized mice and suggests that targeting TGR5 within the GM may have therapeutic potential for postmenopausal osteoporosis.
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Microbioma Gastrointestinal , Osteoporosis Posmenopáusica , Humanos , Femenino , Ratones , Animales , Osteoporosis Posmenopáusica/tratamiento farmacológico , Receptores Acoplados a Proteínas G/metabolismo , Densidad Ósea , Estrógenos/uso terapéuticoRESUMEN
RESEARCH QUESTION: Does blastocyst biopsy for preimplantation genetic testing (PGT) increase the risk of adverse maternal and neonatal outcomes? STUDY DESIGN: Retrospective cohort study of 5097 single vitrified-warmed blastocyst transfer cycles from January 2016 to December 2018, with 2061 cycles in the biopsied group and 3036 cycles in the unbiopsied group enrolled in the analyses. Maternal and neonatal outcomes were compared between the two groups. RESULTS: The live birth rate in the biopsied group (41.1%) was significantly higher than that in the unbiopsied group (35.6%, adjusted odds ratio [aOR] 1.27, 95% confidence interval [CI] 1.05-1.54, Pâ¯=â¯0.012) after adjusting for maternal age, maternal body mass index, gravidity, parity, infertility diagnosis, timing of blastocyst transfer, blastocyst quality, regimen of endometrial preparation, endometrial thickness before transfer and treatment year. The rates of total pregnancy loss (25.4% versus 32.2%, aOR 0.69, 95% CI 0.52-0.91, Pâ¯=â¯0.008) and early miscarriage (12.1% versus 17.3%, aOR 0.56, 95% CI 0.38-0.83, Pâ¯=â¯0.004) were significantly lower in the biopsied group than in the unbiopsied group. No significant differences were found in sex ratio or the risks of hypertensive disorders in pregnancy, diabetes in pregnancy, placenta previa, preterm premature rupture of membranes, low birthweight, very low birthweight, macrosomia, small for gestational age, large for gestational age or birth defects between the two groups. When the subgroup analyses were conducted based on different types of PGT, similar patterns were found for all types. CONCLUSION: Blastocyst biopsy might not increase the risks of adverse maternal and neonatal outcomes in the short term.
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Aborto Espontáneo , Blastocisto , Biopsia , Blastocisto/patología , Transferencia de Embrión , Femenino , Pruebas Genéticas , Humanos , Recién Nacido , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Transferencia de un Solo EmbriónRESUMEN
INTRODUCTION: This study aimed to observe the effects of long-term alendronate pretreatment on the healing of osteoporotic calvarial defects, and further investigate the effect of alendronate combined with once-weekly parathyroid hormone following 12 weeks of alendronate treatment in ovariectomized rats. MATERIALS AND METHODS: Thirty 3-month-old female rats were ovariectomized, and 24 rats received alendronate for 12 weeks. Then, a critical defect was created in the calvaria of all animals. Immediately after osteotomy, the animals received one of five treatments for 8 weeks: (1) continuation of vehicle (group E), (2) alendronate followed by vehicle (group A), (3) continuation of alendronate (group B), (4) alendronate followed by once-weekly parathyroid hormone alone (group C), or (5) continuation of alendronate combined with once-weekly parathyroid hormone (group D). Calvarial defect healing was assessed using dual-energy X-ray absorptiometry, micro-computed tomography, histology, and sequential fluorescence labeling. RESULTS: Group E showed a significantly higher volume of newly formed bone than groups A, B, C, and D. Evidence of new dense bone formation in group E was observed histologically. In addition, the immunohistochemical expression of runt-related transcription factor 2 was increased in group E but inhibited in groups A, B, C, and D. Sequential immunofluorescence also showed inhibited mineral apposition in groups A, B, C, and D compared with group E. CONCLUSION: The present study shows that long-term pretreatment with alendronate inhibited calvarial defect healing in osteoporotic rats, and this effect could not be reversed by stopping alendronate, switching to parathyroid hormone, or combining with once-weekly parathyroid hormone.
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Alendronato , Densidad Ósea , Absorciometría de Fotón , Alendronato/farmacología , Animales , Femenino , Hormona Paratiroidea , Ratas , Microtomografía por Rayos XRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by the development of renal cysts and progression to renal failure. Preimplantation genetic testing-monogenic disease (PGT-M) is an alternative option to obtain healthy babies. However, de novo PKD1 mutation of one of the spouses or the absence of a positive family history poses a serious challenge to PGT-M. Here, we described a comprehensive strategy which includes preimplantation genetic testing for aneuploidies (PGT-A) study and monogenic diagnosis study for ADPKD patients bearing de novo mutations. The innovation of our strategy is to use the gamete (polar body or single sperm) as proband for single-nucleotide polymorphism (SNP) linkage analysis to detect an embryo's carrier status. Nine ADPKD couples with either de novo mutation or without a positive family history were recruited and a total of 34 embryos from 13 PGT-M cycles were examined. Within these nine couples, two successfully delivered healthy babies had their genetic status confirmed by amniocentesis. This study provides a creative approach for embryo diagnosis of patients with de novo mutations or patients who lack essential family members for linkage analysis.
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Aneuploidia , Pruebas Genéticas/métodos , Nacimiento Vivo/epidemiología , Mutación , Riñón Poliquístico Autosómico Dominante/diagnóstico , Diagnóstico Preimplantación/métodos , Canales Catiónicos TRPP/genética , Adulto , Transferencia de Embrión , Embrión de Mamíferos/metabolismo , Embrión de Mamíferos/patología , Femenino , Fertilización In Vitro , Ligamiento Genético , Células Germinativas/metabolismo , Células Germinativas/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Riñón Poliquístico Autosómico Dominante/epidemiología , Riñón Poliquístico Autosómico Dominante/genética , Embarazo , Adulto JovenRESUMEN
PURPOSE: To determine whether next-generation sequencing (NGS) could be used to directly detect different mutations of Duchenne muscular dystrophy (DMD) during preimplantation genetic testing (PGT). METHODS: From Sep. 2016 to Aug. 2018, a total of six couples participated in this study. Four cases carried DMD exon deletions and two carried exon duplications. Trophectoderm cells were biopsied at day 5 or 6 and NGS was used in the genetic testing of the biopsied cells after whole-genome amplification. We developed a new method-DIRected Embryonic Cell Testing of Exon Deletion/Duplication (DIRECTED) to directly detect the single-gene mutation by NGS. Linage analysis based on single-nucleotide polymorphism (SNP) was used to validate the results from DIRECTED. RESULTS: In the four deletion cases, DIRECTED was used to detect DMD exon deletion in 16 biopsied embryos. All DIRECTED results were consistent with linkage analysis, indicating this method was reliable in detecting deletions around 1 Mb. In the two cases carrying exon duplications, no blastocyst was obtained for biopsy. Nonetheless, preliminary experiment results suggested that DIRECTED could also be used for direct detection of exon duplications in embryos. CONCLUSIONS: Exon deletions or duplications in DMD of preimplantation embryos could be detected directly by NGS-based methods during PGT.
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Distrofina/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Distrofia Muscular de Duchenne/diagnóstico , Diagnóstico Preimplantación , Adulto , Biopsia , Blastocisto/metabolismo , Blastocisto/patología , Exones/genética , Femenino , Eliminación de Gen , Tamización de Portadores Genéticos , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Secuenciación de Nucleótidos de Alto Rendimiento/tendencias , Humanos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patología , Mutación/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
BACKGROUND: Hip fracture is a public health concern because of its considerable morbidity, excess mortality, great risk of disability, and high societal healthcare costs. China has the largest population of older people in the world and is experiencing rapid population aging and facing great challenges from an increasing number of hip fractures. However, few studies reported the epidemiology, especially at a national level. We aimed to evaluate trends in hip fracture incidence and associated costs for hospitalization in China. METHODS AND FINDINGS: We conducted a population-based study using data between 2012 and 2016 from the national databases of Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance in China, covering about 480 million residents. Data from around 102.56 million participants aged 55 years and older during the study period were analyzed. A total of 190,560 incident hip fracture patients (mean age 77.05 years, standard deviation 8.94; 63.99% female) were identified. Primary outcomes included the age- and sex-specific incidences of hip fracture. Associated annual costs for hospitalization were also calculated. Incidence was described as per 100,000 person-years at risk, and 95% confidence intervals were computed assuming a Poisson distribution. Hip fracture incidence overall in China did not increase during the study period despite rapid population aging. Incidence per 100,000 was 180.72 (95% CI 137.16, 224.28; P < 0.001) in 2012 and 177.13 (95% CI 139.93, 214.33; P < 0.001) in 2016 for females, and 121.86 (95% CI 97.30, 146.42; P < 0.001) in 2012 and 99.15 (95% CI 81.31, 116.99; P < 0.001) in 2016 for males. For both sexes, declines in hip fracture incidence were observed in patients aged 65 years and older, although incidence was relatively stable in younger patients. However, the total absolute number of hip fractures in those 55 years and older increased about 4-fold. The total costs for hospitalization showed a steep rise from US$60 million to US$380 million over the study period. Costs for hospitalization per patient increased about 1.59-fold, from US$4,300 in 2012 to US$6,840 in 2016. The main limitation of the study was the unavailability of data on imaging information to adjudicate cases of hip fracture. CONCLUSIONS: Our results show that hip fracture incidence among patients aged 55 and over in China reached a plateau between 2012 and 2016. However, the absolute number of hip fractures and associated medical costs for hospitalization increased rapidly because of population aging.
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Fracturas de Cadera/diagnóstico , Fracturas de Cadera/epidemiología , Vigilancia de la Población , Población Urbana/tendencias , Anciano , Anciano de 80 o más Años , China/epidemiología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Gut microbiota dysbiosis has been studied under the pathological conditions of osteoarthritis (OA). However, the effect of antibiotic-induced gut flora dysbiosis on OA remains incompletely understood at present. Herein, we used a mouse (8 weeks) OA model of destabilization of the medial meniscus (DMM) and gut microbiome dysbiosis induced by antibiotic treatment with ampicillin and neomycin for 8 weeks. The results show that antibiotic-induced intestinal microbiota dysbiosis reduced the serum level of lipopolysaccharide (LPS) and the inflammatory response, such as suppression of the levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which can lead to decreased matrix metalloprotease-13 (MMP-13) expression and improvement of OA after joint injury. In addition, trabecular thickness (Tb.Th) and osteophyte scores were increased significantly in antibiotic-induced male mice compared with female mice. We further used network correlation analysis to verify the effect of gut microbiota dysbiosis on OA. Therefore, the present study contributes to our understanding of the gut-joint axis in OA and reveals the relationship between the inflammatory response, sex and gut microbiota, which may provide new strategies to prevent the symptoms and long-term sequelae of OA. Conclusion: Our data showed that gut microbiome dysbiosis alleviates the progression of OA.
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Progresión de la Enfermedad , Disbiosis/microbiología , Microbioma Gastrointestinal , Osteoartritis/microbiología , Osteoartritis/patología , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Biomarcadores/sangre , Huesos/efectos de los fármacos , Huesos/patología , Calcificación Fisiológica/efectos de los fármacos , Cartílago/efectos de los fármacos , Cartílago/patología , Disbiosis/sangre , Disbiosis/complicaciones , Disbiosis/tratamiento farmacológico , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Inflamación/patología , Masculino , Metaloproteinasa 13 de la Matriz/metabolismo , Meniscos Tibiales/efectos de los fármacos , Meniscos Tibiales/patología , Ratones Endogámicos C57BL , Esclerosis/complicaciones , Esclerosis/patología , Caracteres SexualesRESUMEN
LINE-1 is an autonomous non-LTR retrotransposon in mammalian genomes and encodes ORF1P and ORF2P. ORF2P has been clearly identified as the enzyme supplier needed in LINE-1 retrotransposition. However, the role of ORF1P is not well explored. In this study, we employed loss/gain-of-function approach to investigate the role of LINE1-ORF1P in mouse oocyte meiotic maturation. During mouse oocyte development, ORF1P was observed in cytoplasm as well as in nucleus at germinal vesicle (GV) stage while was localized on the spindle after germinal vesicle breakdown (GVBD). Depletion of ORF1P caused oocyte arrest at the GV stage as well as down-regulation of CDC2 and CYCLIN B1, components of the maturation-promoting factor (MPF). Further analysis demonstrated ORF1P depletion triggered DNA damage response and most of the oocytes presented altered chromatin configuration. In addition, SMAD4 showed nuclear foci signal after Orf1p dsRNA injection. ORF1P overexpression held the oocyte development at MI stage and the chromosome alignment and spindle organization were severely affected. We also found that ORF1P could form DCP1A body-like foci structure in both cytoplasm and nucleus after heat shock. Taken together, accurate regulation of ORF1P plays an essential role in mouse oocyte meiotic maturation.
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Elementos de Nucleótido Esparcido Largo/genética , Meiosis/genética , Oocitos/citología , Oogénesis/fisiología , Proteínas de Unión al ARN/metabolismo , Animales , Proteína Quinasa CDC2/metabolismo , Ciclina B1/metabolismo , Reparación del ADN/genética , Endorribonucleasas/metabolismo , Femenino , Factor Promotor de Maduración/metabolismo , Mesotelina , Ratones , Ratones Endogámicos ICR , ARN Mensajero/genética , Proteínas de Unión al ARN/genética , Proteína Smad4/metabolismo , Huso Acromático/metabolismo , Transactivadores/metabolismoRESUMEN
BACKGROUND: Abnormal serum lipid levels have been shown to be associated with the occurrence of atherosclerosis, but little is known about the relationships of them with the risk of developing intervertebral disc degeneration (IVDD) in Chinese population. METHODS: We performed a case-control study to assess the relationship between serum lipid levels and lumbar disc degeneration. A total of 790 Chinese patients were recruited for this study at the time of hospitalization. We examined fasting serum lipid levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). 396 patients (235 men and 161 women; mean age: 41.07 years) underwent surgery for single-level lumbar disc herniation. A control group of 394 patients (225 men and 169 women; mean age: 42.1 years) underwent surgery for wounded lower limbs during the same period. Patients in the control group were collected randomly from among patients who were age- and sex-matched patients with the case group. RESULTS: Patients with lumbar disc herniation had significantly higher TC and LDL-C serum concentrations (P < 0.001 for both) than controls. Percentage of High-TC, High-TG, High-LDL-C, borderline High-TC and borderline High-LDL-C were significantly higher in the disc herniation group (P = 0.017, P = 0.002, P = 0.039, P =0.002 and P < 0.001, respectively). Ratios of TC/HDL-C and LDL-C/HDL-C were significantly associated with disc herniation (P < 0.001 for both). Logistic regression revealed that patients with higher serum LDL-C levels had a higher risk of disc herniation, in which odds ratio (OR) was 1.462 and confidence interval (CI) was 1.179 ~ 1.813. Moreover, patients with High-TG and borderline High-LDL-C had a higher probability of disc herniation (OR: 2.974, CI: 1.488 ~ 5.945, statistical power: 100%; OR: 1.626, CI: 1.012 ~ 2.612, statistical power: 61.4%, respectively). However, hyperlipidaemia did not seem to be associated with the herniated segment of the lumbar intervertebral disc (p = 0.374). CONCLUSIONS: The present study suggests that dyslipidaemia may be associated with a higher risk of developing lumbar disc herniation. Serum lipid levels could be a useful predictor for intervertebral disc degeneration in Chinese population.
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Desplazamiento del Disco Intervertebral/sangre , Lípidos/sangre , Vértebras Lumbares/fisiopatología , Adulto , Pueblo Asiatico , Estudios de Casos y Controles , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dislipidemias/sangre , Femenino , Humanos , Hiperlipidemias/sangre , Desplazamiento del Disco Intervertebral/etiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Triglicéridos/sangreRESUMEN
Excessive salt intake is a widespread health issue observed in almost every country around the world. A high salt diet (HSD) has a strong correlation with numerous diseases, including hypertension, chronic kidney disease, and autoimmune disorders. However, the mechanisms underlying HSD-promotion of inflammation and exacerbation of these diseases are not fully understood. In this study, we observed that HSD consumption reduced the abundance of the gut microbial metabolite L-fucose, leading to a more substantial inflammatory response in mice. A HSD led to increased peritonitis incidence in mice, as evidenced by the increased accumulation of inflammatory cells and elevated levels of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1, also known as C-C motif chemokine ligand 2 or CCL2), in peritoneal lavage fluid. Following the administration of broad-spectrum antibiotics, HSD-induced inflammation was abolished, indicating that the proinflammatory effects of HSD were not due to the direct effect of sodium, but rather to HSD-induced alterations in the composition of the gut microbiota. By using untargeted metabolomics techniques, we determined that the levels of the gut microbial metabolite L-fucose were reduced by a HSD. Moreover, the administration of L-fucose or fucoidan, a compound derived from brown that is rich in L-fucose, normalized the level of inflammation in mice following HSD induction. In addition, both L-fucose and fucoidan inhibited LPS-induced macrophage activation in vitro. In summary, our research showed that reduced L-fucose levels in the gut contributed to HSD-exacerbated acute inflammation in mice; these results indicate that L-fucose and fucoidan could interfere with HSD-promotion of the inflammatory response.
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Fucosa , Polisacáridos , Cloruro de Sodio Dietético , Ratones , Animales , Fucosa/farmacología , Inflamación/metabolismo , DietaRESUMEN
Pathogens in drinking water remain a challenge for human health, photo-Fenton process is a promising technique for pathogen inactivation, herein, two common iron oxides, hematite and magnetite mediate persulfate (peroxymonosulfate-PMS - and peroxydisulfate-PDS) involved photo-Fenton-like processes were constructed for E. coli inactivation, and the inactivation performance was investigated and compared with the photo-Fenton process under a low intensity UVA irradiation. Results indicated that with a low dose of iron oxides (1 mg/L) and inorganic peroxides (10 mg/L), PMS-involved photo-Fenton-like process is the best substitute for the photo-Fenton one over pH range of 5-8. In addition, humic acid (HA, one of the important components of natural organic matter) incorporated iron oxide-mediated photo-Fenton-like processes for bacteria inactivation was also studied, and facilitating effect was found in UVA/hematite/PMS and UVA/magnetite/PDS systems. Reactive oxygen species (ROS) exploration experiments revealed that ·OH was the predominant radical in H2O2- and PDS-containing systems, whereas 1O2 was one of the principal reactive species in the PMS systems. In addition to the semiconductor photocatalysis of iron oxides and UVA-activated oxidants, iron-complexes (iron-oxidant complexes and iron-bacteria complexes) mediated ligand-to-metal charge transfer (LMCT) processes also made contribution to bacterial inactivation. Overall, this study demonstrates that it is feasible to replace H2O2 with PMS in a photo-Fenton-like process for water disinfection using a low dose of reagents, mediated by cheap catalysts, such as hematite and magnetite, it is also hoped to provide some insights to practical water treatment.
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Desinfectantes , Compuestos Férricos , Rayos Ultravioleta , Compuestos Férricos/química , Desinfectantes/farmacología , Peróxido de Hidrógeno/química , Oxidantes/química , Escherichia coli/efectos de los fármacos , Desinfección/métodos , Especies Reactivas de Oxígeno/metabolismo , Purificación del Agua/métodos , Peróxidos/químicaRESUMEN
The photo-Fenton process is effective for pathogen removal, and its low-cost versions can be applied in resource-poor contexts. Herein, a photo-Fenton-like system was proposed using low concentrations of iron oxides (hematite and magnetite) and persulfates (peroxymonosulfate - PMS, and peroxydisulfate - PDS), which exhibited excellent inactivation performance towards MS2 bacteriophages. In the presence of bacteria, MS2 inactivation was inhibited in H2O2 and PDS systems but promoted in PMS-involved systems. The inactivation efficacy of all the proposed systems for mixed bacteria and viruses was greater than that of the sole bacteria, showing potential practical applications. The inactivation performance of humic acid-incorporated iron oxides mediating photo-Fenton-like processes was also studied; except for the PMS-involved system, the inactivation efficacy of the H2O2- and PDS-involved systems was inhibited, but the PDS-involved system was still acceptable (< 2 h). Reactive species exploration experiments indicated that ·OH was the main radical in the H2O2 and PDS systems, whereas 1O2 played a key role in the PMS-involved system. In summary, hematite- and magnetite-mediated persulfate-assisted photo-Fenton-like systems at low concentrations can be used as alternatives to the photo-Fenton process for virus inactivation in sunny areas, providing more possibilities for point-of-use drinking water treatment in developing countries.
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Compuestos Férricos , Peróxido de Hidrógeno , Peróxido de Hidrógeno/química , Compuestos Férricos/química , Concentración de Iones de Hidrógeno , Purificación del Agua/métodos , Sulfatos/química , Peróxidos/químicaRESUMEN
Preimplantation genetic testing (PGT) can minimize the risk of birth defects. However, the accuracy and applicability of routine PGT is confounded by uneven genome coverage and high allele drop-out rate from existing single-cell whole genome amplification methods. Here, a method to diagnose genetic mutations and concurrently evaluate embryo competence by leveraging the abundant mRNA transcript copies present in trophectoderm cells is developed. The feasibility of the method is confirmed with 19 donated blastocysts. Next, the method is applied to 82 embryos from 26 families with monogenic defects for simultaneous mutation detection and competence assessment. The accuracy rate of direct mutation detection is up to 95%, which is significantly higher than DNA-based method. Meanwhile, this approach correctly predicted seven out of eight (87.5%) embryos that failed to implant. Of six embryos that are predicted to implant successfully, four met such expectations (66.7%). Notably, this method is superior at conditions for mutation detection that are challenging when using DNA-based PGT, such as when detecting pathogenic genes with a high de novo rate, multiple pseudogenes, or an abnormal expansion of CAG trinucleotide repeats. Taken together, this study establishes the feasibility of an RNA-based PGT that is also informative for assessing implantation competence.
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Pruebas Genéticas , Diagnóstico Preimplantación , Humanos , Diagnóstico Preimplantación/métodos , Femenino , Pruebas Genéticas/métodos , Blastocisto/metabolismo , Embarazo , Transcriptoma/genética , Mutación/genéticaRESUMEN
Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, but its diagnosis and treatment remain obscure. Non-coding RNAs (ncRNAs), as potential biomarkers, have attracted increasing attention in digestive diseases. Here, we present a comprehensive research status, development trends, and valuable insights in this subject area. The literature search was performed using Web of Science Core Collection. VOSviewer 1.6.20, Citespace 6.2.R4, and Microsoft Excel 2021 were used for bibliometric analysis. A total of 124 articles were included in the analysis. Overall, publication patterns fluctuated. Globally, People's Republic of China, the USA, and Germany were the top three contributors of publications. Guangzhou University of Chinese Medicine, University of California, Mayo Clinic, and University of California, Los Angeles contributed the highest number of publications. The pathways and specific mechanisms by which ncRNAs regulate transcription and translation and thus regulate the pathophysiological processes of IBS are the main research hotspots in this field. We found that microRNA (miRNAs) are intricately involved in the regulation of key pathologies such as viscera sensitivity, intestinal permeability, intestinal mucosal barrier, immunoinflammatory response, and brain-gut axis in the IBS, and these topics have garnered significant attention in research community. Notably, microecological disorders are also associated with IBS pathogenesis, and ncRNA may play an important role in the interactions between host and intestinal flora. This is the first bibliometric study to comprehensively summarize the research hotspots and trends related to IBS and ncRNAs (especially miRNAs). Our findings will help understand the role of ncRNAs in IBS and provide guidance to future studies.
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Bibliometría , Síndrome del Colon Irritable , MicroARNs , Humanos , Síndrome del Colon Irritable/genética , MicroARNs/genéticaRESUMEN
The well known and most important function of nucleoli is ribosome biogenesis. However, the nucleolus showed delayed development and malfunction in somatic cell nuclear transfer (NT) embryos. Previous studies indicated that nearly half rRNA genes (rDNA) in somatic cells were inactive and not transcribed. We compared the rDNA methylation level, active nucleolar organizer region (NORs) numbers, nucleolar proteins (upstream binding factor (UBF), nucleophosmin (B23)) distribution, and nucleolar-related gene expression in three different donor cells and NT embryos. The results showed embryonic stem cells (ESCs) had the most active NORs and lowest rDNA methylation level (7.66 and 6.76%), whereas mouse embryonic fibroblasts (MEFs) were the opposite (4.70 and 22.57%). After the donor cells were injected into enucleated MII oocytes, cumulus cells and MEFs nuclei lost B23 and UBF signals in 20 min, whereas in ESC-NT embryos, B23 and UBF signals could still be detected at 60 min post-NT. The embryos derived from ESCs, cumulus cells, and MEFs showed the same trend in active NORs numbers (7.19 versus 6.68 versus 5.77, p < 0.05) and rDNA methylation levels (6.36 versus 9.67% versus 15.52%) at the 4-cell stage as that in donor cells. However, the MEF-NT embryos displayed low rRNA synthesis/processing potential at morula stage and had an obvious decrease in blastocyst developmental rate. The results presented clear evidences that the rDNA reprogramming efficiency in NT embryos was determined by the rDNA activity in donor cells from which they derived.
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Blastocisto/metabolismo , Nucléolo Celular/metabolismo , Metilación de ADN , ADN Ribosómico/metabolismo , Genes de ARNr , Técnicas de Transferencia Nuclear , Procesamiento Postranscripcional del ARN , Animales , Femenino , Masculino , Ratones , Proteínas Nucleares/metabolismo , Nucleofosmina , Factores de TiempoRESUMEN
A number of germ cell-specific transcription factors essential for ovarian formation and folliculogenesis have been identified and studied. However, the role of these factors during early embryonic development has been poorly explored. In the present study, we investigated the role of SEBOX, a maternal homeobox transcription factor, during early embryonic development in porcine parthenotes. mRNA for SEBOX is preferentially expressed in oocytes, and expression persists until embryonic genome activation (EGA). Knockdown of SEBOX by siRNA disrupted early embryonic development, but not oocyte maturation. Many maternal genes essential for early embryonic development were upregulated in SEBOX-depleted embryos. Moreover, some pluripotency-associated genes, including SOX2 and NANOG, were upregulated when SEBOX was knocked down. Therefore, our data demonstrate that SEBOX is required for early embryonic development in pigs and appears to regulate the degradation of maternal transcripts and the expression of pluripotency genes.
Asunto(s)
Blastocisto/metabolismo , Ectogénesis , Embrión de Mamíferos/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Oocitos/metabolismo , Mataderos , Animales , Blastocisto/citología , Células Cultivadas , Células del Cúmulo/citología , Células del Cúmulo/metabolismo , Técnicas de Cultivo de Embriones , Embrión de Mamíferos/citología , Femenino , Células de la Granulosa/citología , Células de la Granulosa/metabolismo , Proteínas de Homeodominio/antagonistas & inhibidores , Proteínas de Homeodominio/genética , Técnicas de Maduración In Vitro de los Oocitos , Oocitos/citología , Partenogénesis , Interferencia de ARN , Estabilidad del ARN , ARN Mensajero/metabolismo , ARN Interferente Pequeño , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Sus scrofa , Regulación hacia ArribaRESUMEN
[This corrects the article DOI: 10.3389/fsurg.2022.939096.].
RESUMEN
A novel catalytic system for effective photocatalytic inactivation of Escherichia coli (E. coli) was constructed by anchoring Ag nanoparticles (AgNPs) on silane coupling agent (SCA) pretreated TiO2 nano-tube arrays (Ag/SCA/TiO2NTAs). Morphology and structural analyses revealed that SCA could disperse AgNPs evenly on TiO2NTAs, thus inducing a superior surface plasmon resonance (SPR) effect. Ag/SCA/TiO2NTAs catalyst exhibited excellent inactivation performance when in the presence of peroxymonosulfate (PMS) and visible light (VL), with 6-log E. coli was completely inactivated within 60 min, which was 5.3, 12.5 and 13.2 times higher than that of Ag/SCA/TiO2NTAs/VL, PMS/VL and Ag/SCA/TiO2NTAs/PMS/dark systems, respectively. Additionally, the photocatalyst exhibited a highly reusable property, with the inactivation performance almost unchanged after ten cycles of uses with minimal Ag leaching. The inactivation mechanism analysis demonstrated that both radical (SO4â¢-, OH) and non-radical (h+, 1O2) pathways involved in E. coli inactivation, and SCA played a pivotal role in the production of reactive species. Chloride ions (Cl-) greatly enhanced the inactivation efficiency, while bicarbonate (HCO3-) and phosphate (H2PO4-) showed an inhibitory effect. Humic acid (HA) displayed a dual effect on inactivation performance, where the low concentration of HA facilitated the bacteria inactivation, while the higher dose suppressed bacteria inactivation. Moreover, the system exhibited excellent inactivation performance in tap water. This work first used SCA as the binder to fix AgNPs on TiO2NTAs for VL photocatalytic inactivation of bacteria with the assistance of PMS, which was expected to provide some insights into the practical treatment of drinking water.