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Leymus chinensis, a dominant perennial grass in the Eurasian Steppe, is well known for its remarkable adaptability and forage quality. Hardly any breeding has been done on the grass, limiting its potential in ecological restoration and forage productivity. To enable genetic improvement of the untapped, important species, we obtained a 7.85-Gb high-quality genome of L. chinensis with a particularly long contig N50 (318.49 Mb). Its allotetraploid genome is estimated to originate 5.29 million years ago (MYA) from a cross between the Ns-subgenome relating to Psathyrostachys and the unknown Xm-subgenome. Multiple bursts of transposons during 0.433-1.842 MYA after genome allopolyploidization, which involved predominantly the Tekay and Angela of LTR retrotransposons, contributed to its genome expansion and complexity. With the genome resource available, we successfully developed a genetic transformation system as well as the gene-editing pipeline in L. chinensis. We knocked out the monocot-specific miR528 using CRISPR/Cas9, resulting in the improvement of yield-related traits with increases in the tiller number and growth rate. Our research provides valuable genomic resources for Triticeae evolutionary studies and presents a conceptual framework illustrating the utilization of genomic information and genome editing to accelerate the improvement of wild L. chinensis with features such as polyploidization and self-incompatibility.
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Fitomejoramiento , Poaceae , Poaceae/genética , Genoma , Evolución MolecularRESUMEN
Adenomyosis (ADS) is a common gynecological disorder, and its pathogenesis remains unclear. This study explores the functions of circRNAs in the eutopic endometrium of ADS and their diagnostic efficacy for ADS. High-throughput RNA sequencing was performed on 12 eutopic endometrial samples from ADS patients and 3 control endometrial samples. Additionally, circRNAs were analyzed in conjunction with clinical features. A competitive endogenous RNA network was established based on bioinformatics analysis, comprising 3 circRNAs, 1 miRNA, and 13 mRNAs. In the ADS group, the expression levels of hsa_circ_0008959 and SLC15A4 were significantly reduced, while hsa-miR-124-3p expression was increased. SLC15A4 was associated with cell proliferation and invasion. Decreased expression of hsa_circ_0008959 and SLC15A4, along with high VAS scores and elevated hsa-miR-124-3p levels, were identified as risk factors for ADS development. The combination of hsa_circ_0008959 and VAS scores demonstrated the highest diagnostic value for ADS.
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Advanced bifunctional electrocatalysts are essential for propelling overall water splitting (OWS) progress. Herein, relying on the obvious difference in the work function of Ir (5.44 eV) and CoMoO4 (4.03 eV) and the constructed built-in electric field (BEF), an Ir/CoMoO4/NF heterogeneous catalyst, with ultrafine Ir nanoclusters (1.8 ± 0.2 nm) embedded in CoMoO4 nanosheet arrays on the surface of nickel foam skeleton, is reported. Impressively, the Ir/CoMoO4/NF shows remarkable electrocatalytic bifunctionality toward hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), especially at large current densities, requiring only 13 and 166 mV to deliver 10 and 1000 mA cm-2 for HER and 196 and 318 mV for OER. Furthermore, the Ir/CoMoO4/NF||Ir/CoMoO4/NF electrolyzer demands only 1.43 and 1.81 V to drive 10 and 1000 mA cm-2 for OWS. Systematical theoretical calculations and tests show that the formed BEF not only optimizes interfacial charge distribution and the Fermi level of both Ir and CoMoO4, but also reduces the Gibbs free energy (ΔGH*, from 0.25 to 0.03 eV) and activation energy (from 13.6 to 8.9 kJ mol-1) of HER, the energy barrier (from 3.47 to 1.56 eV) and activation energy (from 21.1 to 13.9 kJ mol-1) of OER, thereby contributing to the glorious electrocatalytic bifunctionality.
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Improving local bone mineral density (BMD) at fracture-prone sites of bone is a clinical concern for osteoporotic fracture prevention. In this study, a featured radial extracorporeal shock wave (rESW) responsive nano-drug delivery system (NDDS) is developed for local treatment. Based on a mechanic simulation, a sequence of hollow zoledronic acid (ZOL)-contained nanoparticles (HZNs) with controllable shell thickness that predicts various mechanical responsive properties is constructed by controlling the deposition time of ZOL and Ca2+ on liposome templates. Attributed to the controllable shell thickness, the fragmentation of HZNs and the release of ZOL and Ca2+ can be precisely controlled with the intervention of rESW. Furthermore, the distinct effect of HZNs with different shell thicknesses on bone metabolism after fragmentation is verified. In vitro co-culture experiments demonstrate that although HZN2 does not have the strongest osteoclasts inhibitory effect, the best pro-osteoblasts mineralization results are achieved via maintaining osteoblast-osteoclast (OB-OC) communication. In vivo, the HZN2 group also shows the strongest local BMD enhancement after rESW intervention and significantly improves bone-related parameters and mechanical properties in the ovariectomy (OVX)-induced osteoporosis (OP) rats. These findings suggest that an adjustable and precise rESW-responsive NDDS can effectively improve local BMD in OP therapy.
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Osteoporosis , Fracturas Osteoporóticas , Femenino , Ratas , Animales , Osteoclastos , Fracturas Osteoporóticas/metabolismo , Liberación de Fármacos , Huesos , Osteoporosis/tratamiento farmacológico , Osteoporosis/prevención & control , Osteoporosis/metabolismo , Osteoblastos , Ácido Zoledrónico/metabolismo , Ácido Zoledrónico/farmacología , Ácido Zoledrónico/uso terapéuticoRESUMEN
Histone acetylation is the earliest and most well-characterized of post-translation modifications. It is mediated by histone acetyltransferases (HAT) and histone deacetylases (HDAC). Histone acetylation could change the chromatin structure and status and further regulate gene transcription. In this study, nicotinamide, a histone deacetylase inhibitor (HDACi), was used to enhance the efficiency of gene editing in wheat. Transgenic immature and mature wheat embryos harboring a non-mutated GUS gene, the Cas9 and a GUS-targeting sgRNA were treated with nicotinamide in two concentrations (2.5 and 5 mM) for 2, 7, and 14 days in comparison with a no-treatment control. The nicotinamide treatment resulted in GUS mutations in up to 36% of regenerated plants, whereas no mutants were obtained from the non-treated embryos. The highest efficiency was achieved when treated with 2.5 mM nicotinamide for 14 days. To further validate the impact of nicotinamide treatment on the effectiveness of genome editing, the endogenous TaWaxy gene, which is responsible for amylose synthesis, was tested. Utilizing the aforementioned nicotinamide concentration to treat embryos containing the molecular components for editing the TaWaxy gene, the editing efficiency could be increased to 30.3% and 13.3%, respectively, for immature and mature embryos in comparison to the 0% efficiency observed in the control group. In addition, nicotinamide treatment during transformation progress could also improve the efficiency of genome editing approximately threefold in a base editing experiment. Nicotinamide, as a novel approach, may be employed to improve the editing efficacy of low-efficiency genome editing tools such as base editing and prime editing (PE) systems in wheat.
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Edición Génica , Triticum , Edición Génica/métodos , Triticum/genética , Sistemas CRISPR-Cas , Histonas/genética , MutaciónRESUMEN
The rational design of advanced nanohybrids (NHs) with optimized interface electronic environment and rapid reaction kinetics is pivotal to electrocatalytic schedule. Herein, we developed a multiple heterogeneous Co9 S8 /Co3 S4 /Cu2 S nanoparticle in which Co3 S4 germinates between Co9 S8 and Cu2 S. Using high-angle annular-dark-field imaging and theoretical calculation, it was found that the integration of Co9 S8 and Cu2 S tends to trigger the interface phase transition of Co9 S8 , leading to Co3 S4 interlayer due to the low formation energy of Co3 S4 /Cu2 S (-7.61â eV) than Co9 S8 /Cu2 S (-5.86â eV). Such phase transition not only lowers the energy barrier of oxygen evolution reaction (OER, from 0.335â eV to 0.297â eV), but also increases charge carrier density (from 7.76×1014 to 2.09×1015 â cm-3 ), and creates more active sites. Compared to Co9 S8 and Cu2 S, the Co9 S8 /Co3 S4 /Cu2 S NHs also demonstrate notable photothermal effect that can heat the catalyst locally, offset the endothermic enthalpy change of OER, and promote carrier migrate, reaction intermediates adsorption/deprotonation to improve reaction kinetics. Profiting from these favorable factors, the Co9 S8 /Co3 S4 /Cu2 S catalyst only requires an OER overpotential of 181â mV and overall water splitting cell voltage of 1.43â V to driven 10â mA cm-2 under the irradiation of near-infrared light, outperforming those without light irradiation and many reported Co-based catalysts.
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KEY MESSAGE: New translocation lines with T6V#4S·6AL in the Ph1 and ph1b backgrounds were developed with improved inheritance of powdery mildew resistance. The wheat-Dasypyrum villosum T6V#4S·6DL translocation line Pm97033, which exhibits strong powdery mildew (PM) resistance, was developed many years ago, but has limited application in wheat breeding. One of the major reasons for this is that the translocation chromosome has low transmission rate, which makes it difficult to obtain ideal genotype through recombination with other elite agronomic traits in a limited segregating population. Further modifications are thus needed to make better use of this genetic resource. In this study, Pm97033 and the T6V#2S·6AL translocation line NY-W were hybridized with the CS ph1b mutant, and two F1 hybrids were hybridized with each other. Then, plants homozygous for the ph1b deletion carrying the alien chromosome arm(s) 6V#2S and 6V#4S were identified from the segregating populations using molecular markers. New T6V#4S·6AL and T6V#2-6V#4S·6AL translocations were identified by molecular markers and confirmed by genomic in situ hybridization (GISH). Individuals that were heterozygous or homozygous for the translocation chromosome in Ph1 and ph1b backgrounds were obtained. The ratio of PM resistance vs. susceptibility in the self-pollinated heterozygous plants was 3:1, and the phenotype was completely consistent with the KASP genotyping. Thus, the new translocation chromosomes had higher transmission rate than the original T6V#4S·6DL, and so can be effectively applied in breeding programs.
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Fitomejoramiento , Triticum , Cromosomas de las Plantas/genética , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Poaceae/genética , Translocación Genética , Triticum/genéticaRESUMEN
RESEARCH QUESTION: What are the prevalence and risk factors of intrauterine adhesions (IUA) in patients with a septate uterus? DESIGN: In this retrospective cohort study, patients with a septate uterus who underwent septum resection between 2015 and 2020 were analysed. Two-dimensional transvaginal ultrasonography plus hysteroscopy was used to diagnose uterine septum or IUA. The prevalence and risk factors for IUA in patients with a septate uterus were examined. RESULTS: Among 522 eligible patients with a septate uterus, 165 patients were diagnosed with IUA (prevalence 31.6% [95% CI 27.7 to 35.5%]). In the multivariable logistic regression analysis of risk factors for IUA, patients who had experienced one or more miscarriages were more likely to have IUA than patients who had not (OR 3.38, 95% CI 1.96 to 5.83, P < 0.001, and OR 2.55, 95% CI 1.24 to 5.23, Pâ¯=â¯0.011, respectively). Patients who underwent one or more dilatation and curettage (D&C) procedures had a significantly increased risk of IUA compared with patients who did not (OR 3.42, 95% CI 1.87 to 6.26, P < 0.001, and OR 3.99, 95% CI 1.93 to 8.26, P < 0.001, respectively). For patients with a history of miscarriage or D&C, the prevalence rates of IUA were 46.5% (95% CI 40.6 to 52.4%) and 44.0% (95% CI 38.5 to 49.5%), respectively. CONCLUSION: Nearly one-third of patients with a septate uterus have concomitant IUA. A previous miscarriage or D&C is an important risk factor for IUA in patients with a septate uterus.
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Aborto Espontáneo , Enfermedades Uterinas , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Femenino , Humanos , Histeroscopía/métodos , Embarazo , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Adherencias Tisulares/epidemiología , Adherencias Tisulares/etiología , Enfermedades Uterinas/cirugía , Útero/diagnóstico por imagen , Útero/cirugíaRESUMEN
PURPOSE: The study aims to evaluate whether frozen embryo transfer can restore optimal receptivity leading to better assisted reproductive technology outcomes in women with endometriosis. METHODS: This systematic review and meta-analysis, conducted from January 10, 2021 to July 1, 2021, searched the Cochrane Library, PubMed, Embase, Web of Science, OVID, and Clinicaltrials.gov databases from inception to January 10, 2021. The search strategy combined search terms as follows: ("endometriosis" OR "deep endometriosis" OR "endometrioma") AND ("frozen-thawed embryo transfer" OR "frozen embryo transfer" OR "freeze-all strategy") AND ("pregnancy outcome" OR "live birth rate" OR "clinical pregnancy rate" OR "miscarriage rate"). No publication time or language limits were set during the searches. In addition, references of the related articles were searched by hand. Patients were included if they had a history of endometriosis and had received fresh or frozen embryo transfer. Only the first transfer cycle was included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to express outcomes, and data synthesis was conducted using RevMan, version 5.4 software. RESULTS: A total of six studies with moderate methodologic quality were retrieved in the meta-analysis. The studies included 3010 women with endometriosis who wanted to conceive; 1777 (59.0%) had frozen embryo transfer, and 1233 (41.0%) had fresh embryo transfer. There was a significantly higher frequency of live births in the frozen embryo group than in the fresh embryo group (OR, 1.53; 95% CI, 1.13-2.08; P = .007). Despite a similar clinical pregnancy rate in the two groups (OR, 1.26; 95% CI, 0.95-1.69; P = .11), the difference in miscarriage rate was significant (OR, 0.70; 95% CI, 0.50-0.97; P = .03). Evidence quality was considered moderate. CONCLUSION: Cryopreserved embryo transfer has resulted in preferable reproduction outcomes when compared with fresh embryo transfer in patients with endometriosis, but the evidence is not yet abundant. More strictly designed research is needed to evaluate whether frozen embryo transfer leads to better reproductive outcomes in women with endometriosis compared with those receiving fresh embryo transfer. REGISTRATION NUMBER: PROSPERO CRD42021248313.
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Aborto Espontáneo , Endometriosis , Infertilidad , Aborto Espontáneo/etiología , Transferencia de Embrión/métodos , Femenino , Humanos , Infertilidad/etiología , Nacimiento Vivo , Embarazo , Índice de EmbarazoRESUMEN
For developing an effective interventional approach and treatment modality for PM2.5, the effects of omega-3 fatty acids on alleviating inflammation and attenuating lung injury induced by inhalation exposure of PM2.5 were assessed in murine models. We found that daily oral administration of the active components of omega-3 fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) effectively alleviated lung parenchymal lesions, restored normal inflammatory cytokine levels and oxidative stress levels in treating mice exposed to PM2.5 (20 mg/kg) every 3 days for 5 times over a 14-day period. Especially, CT images and the pathological analysis suggested protective effects of DHA and EPA on lung injury. The key molecular mechanism is that DHA and EPA can inhibit the entry and deposition of PM2.5, and block the PM2.5-mediated cytotoxicity, oxidative stress, and inflammation.
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Ácidos Grasos Omega-3 , Lesión Pulmonar , Administración Oral , Animales , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/uso terapéutico , Ácido Eicosapentaenoico/farmacología , Ácido Eicosapentaenoico/uso terapéutico , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Inflamación/tratamiento farmacológico , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/etiología , Ratones , Material Particulado/toxicidadRESUMEN
Abscisic acid (ABA) is a key regulator of plant responses to abiotic stresses, such as drought. Abscisic acid receptors and coreceptors perceive ABA to activate Snf1-related protein kinase2s (SnRK2s) that phosphorylate downstream effectors, thereby activating ABA signaling and the stress response. As stress responses come with fitness penalties for plants, it is crucial to tightly control SnRK2 kinase activity to restrict ABA signaling. However, how SnRK2 kinases are inactivated remains elusive. Here, we show that NUCLEAR PORE ANCHOR (NUA), a nuclear pore complex (NPC) component, negatively regulates ABA-mediated inhibition of seed germination and post-germination growth, and drought tolerance in Arabidopsis thaliana. The role of NUA in response to ABA depends on SnRK2.2 and SnRK2.3 for seed germination and on SnRK2.6 for drought. NUA does not directly inhibit the phosphorylation of these SnRK2s or affects their abundance. However, the NUA-interacting protein EARLY IN SHORT DAYS 4 (ESD4), a SUMO protease, negatively regulates ABA signaling by directly interacting with and inhibiting SnRK2 phosphorylation and protein levels. More importantly, we demonstrated that SnRK2.6 can be SUMOylated in vitro, and ESD4 inhibits its SUMOylation. Taken together, we identified NUA and ESD4 as SnRK2 kinase inhibitors that block SnRK2 activity, and reveal a mechanism whereby NUA and ESD4 negatively regulate plant responses to ABA and drought stress possibly through SUMOylation-dependent regulation of SnRK2s.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Poro Nuclear/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
The development of three-dimensional (3D) single-cell imaging and protein quantitative methods can provide more comprehensive information for diagnoses. We report the design and synthesis of a multisignal nanoprobe (AuGdNC@BSA-CV) for single-cell 3D imaging and quantifying the integrin αIIbß3 using correlated synchrotron radiation soft X-ray tomography microscopy and an iterative tomographic algorithm termed equally sloped tomography for the first time. Moreover, on the basis of the Au or Gd content of our nanoprobe, the number of integrin αIIbß3 on a single cell also can be accurately quantified (1.5 × 107 per cell) via inductively coupled plasma mass spectrometry.
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Imagenología Tridimensional , Integrinas/análisis , Nanopartículas/química , Análisis de la Célula Individual , Tomografía Computarizada por Rayos X , Línea Celular Tumoral , Gadolinio/química , Oro/química , Humanos , Albúmina Sérica Bovina/química , SincrotronesRESUMEN
Genitourinary syndrome of menopause (GSM) seriously affects the quality of life of women in this stage and patients with breast cancer, but optimal treatment options as well as risks associated with the complication remain controversial. We aimed at exploring the safest and most effective treatment for genitourinary syndrome of menopause. The study was performed following a pre-established protocol registered on PROSPERO (CRD42020180807). We searched through PubMed, Embase, Scopus, Cochrane Library, Web of Science and ScienceDirect electronic databases, clinicaltrials.gov and OVID for relevant data on Genitourinary syndrome of menopause provided by March 2020. Randomised controlled trials (RCTs) on women presenting with some or all the signs and symptoms for genitourinary syndrome of menopause were extracted and analyzed based on the Bayesian theory. The key variables were additionally evaluated using the network sub-analyses, standard pairwise comparisons, regression analysis and subgroup and sensitivity analyses. The pooled estimates were quantified as odd ratios or mean differences where appropriate, at 95 % confidence intervals. In the end, 29 randomized controlled trials (RCTs) evaluating 5 different treatment regimens for genitourinary syndrome of menopause, involving 8311 patients, were included in the study. Laser therapy had excellent effect on vaginal dryness, dysparunia, urinary incontinence, proportion of parabasal cells, pH and VHI. Vaginal estrogen also had significant effects on these aspects, although its effect was inferior to that of laser therapy. Ospemifene therapy was however superior to laser and vaginal estrogen therapies in ameliorating sexual function, however, it presents a high risk of developing adverse events and endometrial hyperplasia. Moisturizer/lubricant was effective on dysparunia, proportion of parabasal cells and vaginal pH. In regression analysis, age was an essential factor affecting vaginal dryness and pH treatment effect. Compared with other currently available interventional treatments for genitourinary syndrome of menopause, laser therapy, followed by vaginal estrogen, confers superior clinical outcomes for most aspects associated with the disease. In addition, they pose relatively low risks of developing adverse events. Ospemifene and DHEA therapies on their part significantly improve sexual function of women with GSM. A strong relationship between treatment effect and age provides insights for future studies on clinical treatment.
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Enfermedades Urogenitales Femeninas/terapia , Teorema de Bayes , Deshidroepiandrosterona/uso terapéutico , Estrógenos/uso terapéutico , Femenino , Humanos , Terapia por Láser , Menopausia , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome , Tamoxifeno/análogos & derivados , Tamoxifeno/uso terapéutico , Resultado del TratamientoRESUMEN
Heterochromatin is widespread in eukaryotic genomes and has diverse impacts depending on its genomic context. Previous studies have shown that a protein complex, the ASI1-AIPP1-EDM2 (AAE) complex, participates in polyadenylation regulation of several intronic heterochromatin-containing genes. However, the genome-wide functions of AAE are still unknown. Here, we show that the ASI1 and EDM2 mostly target the common genomic regions on a genome-wide level and preferentially interacts with genetic heterochromatin. Polyadenylation (poly(A) sequencing reveals that AAE complex has a substantial influence on poly(A) site usage of heterochromatin-containing genes, including not only intronic heterochromatin-containing genes but also the genes showing overlap with heterochromatin. Intriguingly, AAE is also involved in the alternative splicing regulation of a number of heterochromatin-overlapping genes, such as the disease resistance gene RPP4. We provided evidence that genic heterochromatin is indispensable for the recruitment of AAE in polyadenylation and splicing regulation. In addition to conferring RNA processing regulation at genic heterochromatin-containing genes, AAE also targets some transposable elements (TEs) outside of genes (including TEs sandwiched by genes and island TEs) for epigenetic silencing. Our results reveal new functions of AAE in RNA processing and epigenetic silencing, and thus represent important advances in epigenetic regulation.
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Epigénesis Genética/genética , Empalme Alternativo/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Elementos Transponibles de ADN/genética , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Heterocromatina/genética , Poliadenilación/genética , Poliadenilación/fisiología , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
The aim of this systematic review and meta-analysis was to assess the effect of oestrogen therapy as a preoperative intervention for improving clinical outcomes and fertility outcomes in women with intrauterine adhesions (IUA). A systematic search of PubMed, Embase, The Cochrane Library, clinicaltrials.gov, OVID and Chinese databases was carried out to identify relevant studies published before December 2019. Outcomes were expressed as odds ratios and 95% confidence intervals. Five cohort studies with moderate to high methodological quality were included in the meta-analysis. Preoperative oestrogen therapy was strongly associated with better clinical outcome at second-look hysteroscopy (OR 2.72; 95% CI 1.49 to 4.96; Pâ¯=â¯0.001); whereas no significant difference was found in menstruation improvement and conception rate (OR 1.45; 95% CI, 0.95 to 2.23; Pâ¯=â¯0.09; and OR 0.96; 95% CI 0.60 to 1.54; Pâ¯=â¯0.87, respectively). The overall quality of the evidence ranged from moderate to very low. Preoperative oestrogen therapy may improve the short-term prognosis of IUA at second-look hysteroscopy, whereas the long-term prognosis-fertility outcome was similar to the control group. More strictly designed research studies are needed to assess the effectiveness of oestrogen administration before hysteroscopic adhesiolysis.
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Estrógenos/uso terapéutico , Histeroscopía/métodos , Adherencias Tisulares/cirugía , Enfermedades Uterinas/cirugía , Femenino , Humanos , Cuidados Preoperatorios , PronósticoRESUMEN
The Hedgehog (Hh) pathway effector Gli1 plays an important role in cervical cancer, and GANT61 is an Hh signaling inhibitor. In this study, we aimed to investigate the inhibitory effect of GANT61 on cervical cancer and to study its safety in nude mice. We used in vivo experiments to assess the effect of GANT61 on the growth of cervical cancer HeLa cells, and we measured the WBC, HGB, PLT, ALT, AST and Cre levels in nude mice. Next, we examined the organ and tumor morphology and distant metastasis by HE staining. We used immunohistochemistry to monitor the expression levels of Gli1, FoxM1, Ki-67, cyclinD1, E-cadherin, vimentin, survivin, caspase-3 and CD34+. Western blotting and RT-RCR were used to measure Gli1 expression. GANT61 inhibited the growth and metastasis of HeLa cervical cancer cells upon their transplantation into nude mice, and we preliminarily propose that GANT61 is safe for nude mice. These findings suggest that GANT61 could be used as a Hedgehog inhibitor to inhibit EMT and proliferation and to promote apoptosis via Gli1 downregulation.
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Piridinas/efectos adversos , Piridinas/farmacología , Pirimidinas/efectos adversos , Pirimidinas/farmacología , Alanina Transaminasa/sangre , Animales , Apoptosis/efectos de los fármacos , Aspartato Aminotransferasas/sangre , Plaquetas/metabolismo , Creatinina/sangre , Modelos Animales de Enfermedad , Femenino , Células HeLa , Hemoglobinas/metabolismo , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Especificidad de Órganos , Carga Tumoral , Neoplasias del Cuello Uterino/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The intestinal epithelium is a major barrier that limits the absorption of oral drugs. The integrity of the epithelial tissue is a very important factor for preventing intestinal diseases. However, destabilization of the epithelium can promote the transportation of nanocarriers and increase the absorption of oral drugs. In our research, three different gold nanoparticles (GNPs) of the same size but with differing negative surface charge were designed and constructed as a model to determine the surface properties crucial for promoting absorptivity and bioavailability of the nanocarriers. The higher the ratio of surface carboxyl groups on GNPs, the higher capacity to induce transepithelial electrical resistance change and cell monolayer tight junction opening with higher permeability. The half carboxyl and half methyl surfaced GNPs displayed unique zonal surface patterns exhibited the greater ability to pass through intestinal epithelial cell layer but had a relatively small influence on tight junction distribution.
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Portadores de Fármacos , Enterocitos/metabolismo , Oro , Nanopartículas del Metal/química , Células CACO-2 , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Enterocitos/citología , Oro/química , Oro/farmacocinética , Oro/farmacología , Humanos , PermeabilidadRESUMEN
In eukaryotic cells, gene expression is greatly influenced by the dynamic chromatin environment. Epigenetic mechanisms, including covalent modifications to DNA and histone tails and the accessibility of chromatin, create various chromatin states for stress-responsive gene expression that is important for adaptation to harsh environmental conditions. Recent studies have revealed that many epigenetic factors participate in abiotic stress responses, and various chromatin modifications are changed when plants are exposed to stressful environments. In this review, we summarize recent progress on the cross-talk between abiotic stress response pathways and epigenetic regulatory pathways in plants. Our review focuses on epigenetic regulation of plant responses to extreme temperatures, drought, salinity, the stress hormone abscisic acid, nutrient limitations and ultraviolet stress, and on epigenetic mechanisms of stress memory.
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Epigénesis Genética/genética , Ensamble y Desensamble de Cromatina/genética , Ensamble y Desensamble de Cromatina/fisiología , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Estrés Fisiológico/genética , Estrés Fisiológico/fisiologíaRESUMEN
Osteoclasts are multinucleated terminal cells that originate from a hematopoietic monocyte/macrophage lineage. Excessive osteoclast formation in vivo can lead to bone metabolic diseases such as postmenopausal osteoporosis, multiple myeloma, rheumatoid arthritis, and lytic bone metastases of cancer cells. Au nanoparticles (AuNPs) are inorganic nanoparticles with outstanding biocompatibility. We assessed their effect on osteoclastogenesis and found that pre-osteoclast fusion induced by receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colonystimulating factor (M-CSF) was suppressed by AuNPs. Cell migration and actin ring formation were also significantly inhibited. Finally, AuNPs reduced osteoclast bone absorption function. Interestingly, we observed altered fusogenic gene expression in treated pre-osteoclasts. Our results suggest that AuNPs have potential as a therapeutic agent for osteoclast-related bone metabolism diseases.
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Nanopartículas del Metal , Osteoclastos , Diferenciación Celular , Oro/farmacología , Osteogénesis/genéticaRESUMEN
Small RNAs represent a class of small but powerful agents that regulate development and abiotic and biotic stress responses during plant adaptation to a constantly challenging environment. Previous findings have revealed the important roles of small RNAs in diverse cellular processes. The recent discovery of bidirectional trafficking of small RNAs between different kingdoms has raised many interesting questions. The subsequent demonstration of exosome-mediated small RNA export provided a possible tool for further investigating how plants use small RNAs as a weapon during the arms race between plant hosts and pathogens. This review will focus on discussing the roles of small RNAs in plant immunity in terms of three aspects: the biogenesis of extracellular small RNAs and the transportation and trafficking small RNA-mediated gene silencing in pathogens.