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This report describes a detailed study of Ni phosphine catalysts for the Suzuki-Miyaura coupling of dichloropyridines with halogen-containing (hetero)aryl boronic acids. With most phosphine ligands these transformations afford mixtures of mono- and diarylated cross-coupling products as well as competing oligomerization of the boronic acid. However, a ligand screen revealed that PPh2Me and PPh3 afford high yield and selectivity for monoarylation over diarylation as well as minimal competing oligomerization of the boronic acid. Several key observations were made regarding the selectivity of these reactions, including: (1) phosphine ligands that afford high selectivity for monoarylation fall within a narrow range of Tolman cone angles (between 136° and 157°); (2) more electron-rich trialkylphosphines afford predominantly diarylated products, while less-electron rich di- and triarylphosphines favor monoarylation; (3) diarylation proceeds via intramolecular oxidative addition; and (4) the solvent (MeCN) plays a crucial role in achieving high monoarylation selectivity. Experimental and DFT studies suggest that all these data can be explained based on the reactivity of a key intermediate: a Ni0-π complex of the monoarylated product. With larger, more electron-rich trialkylphosphine ligands, this π complex undergoes intramolecular oxidative addition faster than ligand substitution by the MeCN solvent, leading to selective diarylation. In contrast, with relatively small di- and triarylphosphine ligands, associative ligand substitution by MeCN is competitive with oxidative addition, resulting in selective formation of monoarylated products. The generality of this method is demonstrated with a variety of dichloropyridines and chloro-substituted aryl boronic acids. Furthermore, the optimal ligand (PPh2Me) and solvent (MeCN) are leveraged to achieve the Ni-catalyzed monoarylation of a broader set of dichloroarene substrates.
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Veterinary anatomy plays a crucial role in the curriculum for veterinary medicine and surgery. The integration of modern information technology in veterinary education can greatly benefit from innovative tools such as augmented reality (AR) applications. The aim of this study was to develop an accurate and interactive three-dimensional (3D) digital model of an animal skull using AR technology, aiming to enhance the learning of skull anatomy in veterinary anatomy education. In this study, a canine skull specimen was isolated, and the skull bones were scanned using a structured light scanner to create a 3D digital model of the canine skull, which was found to be indistinguishable from the original specimen by measurement of skull proportions. Furthermore, the interactive AR model of the canine skull, displayed using Unity3D, was subjected to testing and evaluation by 60 first-year veterinary medical students attending the gross anatomy of the animal. The students were divided into two groups: the traditional group and AR group. Both groups completed an objective test and a questionnaire. The evaluation of learning effectiveness in the test revealed no significant difference between the traditional group (which learned using textbooks and a canine skull specimen) and AR group (which learned using AR tools). However, in the questionnaire, students displayed high enthusiasm and interest in using the AR tool. Therefore, the application of AR tools can improve students' motivation for learning and enhance the comprehension of anatomical structures in three dimensions. Furthermore, this study exemplifies the use of AR as an auxiliary tool for teaching and learning in veterinary anatomy education.
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Anatomía , Realidad Aumentada , Educación en Veterinaria , Estudiantes de Medicina , Humanos , Animales , Perros , Educación en Veterinaria/métodos , Anatomía/educación , Cráneo/diagnóstico por imagenRESUMEN
Acute kidney injury (AKI) is closely associated with the overproduction of reactive oxygen species (ROS), which can cause multiple organ dysfunctions without timely treatment. However, only supportive treatments are currently available for AKI in clinics. Here, we developed nanomaterials of hyperbranched polyphosphoester (PPE) containing abundant thioether (S-PPE NP) and thioketal bonds (TK-PPE NP). Our data demonstrates that S-PPE NP exhibits an excellent capability of absorbing and scavenging multiple types of ROS, including H2O2, â¢OH, and â¢O2-, via thioether oxidation to sulfone or sulfoxide; it was also determined that S-PPE NP efficiently eliminates intracellular ROS, thus preventing cellular damage. Moreover, S-PPE NP was able to efficiently accumulate in the injured kidneys of AKI-bearing mice. As a result, the administration of S-PPE NP provided a superior therapeutic effect in AKI-bearing mice by downregulating ROS- and inflammation-related signaling pathways, thus reducing cell apoptosis. This thioether-containing polymer represents a promising broad-spectrum ROS scavenger that can be used for effective AKI treatments.
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Nervous system disease (NSD) is a global health burden with increasing prevalence in the last 30 years. There is evidence that greenness can improve nervous system health through a variety of mechanisms; however, the evidence is inconsistent. In the present systematic review and meta-analysis, we examined the relationship between greenness exposure and NSD outcomes. Studies on the relationship between greenness and NSD health outcomes published till July 2022 were searched in PubMed, Cochrane, Embase, Scopus, and Web of Science. In addition, we searched the cited literature and updated our search on Jan 20, 2023, to identify any new studies. We included human epidemiological studies that assess the association of greenness exposure with the risk of NSD. Greenness exposure was measured using NDVI (the normalized difference vegetation index) and the outcome was the mortality or morbidity of NSD. The pooled relative risks (RRs) were estimated using a random effects model. Of 2059 identified studies, 15 studies were included in our quantitative evaluation, in which 11 studies found a significant inverse relationship between the risk of NSD mortality or incidence/prevalence and an increase in surrounding greenness. The pooled RRs for cerebrovascular diseases (CBVD), neurodegenerative diseases (ND), and stroke mortality were 0.98 (95 % CI: 0.97, 1.00), 0.98 (95 % CI: 0.98, 0.99), and 0.96 (95 % CI: 0.93, 1.00), respectively. The pooled RRs for PD incidence and stroke prevalence/incidence were 0.89 (95 % CI: 0.78, 1.02) and 0.98 (95 % CI: 0.97, 0.99), respectively. The confidence of evidence for ND mortality, stroke mortality, and stroke prevalence/incidence was downgraded to "low", while CBVD mortality and PD incidence were downgraded to "very low" due to inconsistency. We found no evidence of publication bias and the sensitivity analysis results of all subgroups are robust except for the stroke mortality subgroup. This is the first comprehensive meta-analysis of greenness exposure and NSD outcomes in which an inverse relationship was observed. It is necessary to conduct further research to ascertain the role greenness exposure plays in various NSDs and the management of greenness should be considered a public health strategy.
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Trastornos Cerebrovasculares , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/epidemiología , Incidencia , PrevalenciaRESUMEN
With the development of urbanization, ecological space is increasingly disturbed and invaded by human activities. From 2000 to 2020, the value of ecosystem services in China decreased from 28.05 to 27.77 trillion yuan. This paper combines the natural and social data of 370 administrative units in China from 2000 to 2020 with the GTWR model. Our results show that in most regions of China, the coefficient value of factor GDP or POP is significantly higher than that of other factors. The regions with higher natural factors coefficient value are concentrated in the northwest and southeast. In addition, this study found that the driving factors and ESV have geographical spillover effects. The above conclusions have important practical significance for planning policies according to local conditions.
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Efectos Antropogénicos , Ecosistema , Humanos , Urbanización , China , Conservación de los Recursos NaturalesRESUMEN
Age-related changes in human vaginal microbiota composition have been reported, and such changes might be influenced by humidity, external stimuli, hormone levels, drug to use, and other factors. However, there is no report about the vaginal microbiota composition of female beagles at different ages. To investigate the effects of aging on the vaginal microbiota independent of other effects, we analyzed the vaginal microbiomes of 23 beagles at a wide range of ages from 1 year to 7 years old (except the 3rd year), 1-2 y were categorized into youth stage (YS), 4-5 y were categorized into middle stage (MS), and 6-7 y were categorized into elderly stage (ES) based on age. Samples were collected by scraping the vaginal mucosa of YS (n = 8), MS (n = 5) and ES (n = 10), and analyzed by 16S-rRNA gene high-throughput-sequencing. The diversity of the vaginal microbiome in female beagles was found to continuously change with age. We also found associations between age and specific members and functions of the vaginal microbiome. The metabolism of terpenoids and polyketide and the cell motility are significantly enhanced with age. Our results suggest that the proportion of Tenericutes might be a biomarker which could distinguish between YS and others.
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Microbiota , Animales , Perros , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/veterinaria , Humanos , ARN Ribosómico 16S/genética , VaginaRESUMEN
OBJECTIVE: This study aimed to investigate whether liposomal quercetin (LQ) could enhance the effects of microwave ablation (MVA) in treating the rabbit VX2 liver tumor model. METHODS: Rabbits with VX2 liver tumors were randomly divided into three groups: intravenous LQ group (LQ group), MWA group and LQ combined with MWA (LQ + MWA) group. Five rabbits were randomly selected and sacrificed from each group at 12 h and on days 3, 7 and 14 of the operation. The tumor samples were detected and quantified by immunohistochemistry, Western blot, and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: For up to 7 days, the coagulation necrosis volume (CV) of the LQ + MWA group was larger than that of MWA and LQ groups (p < 0.05). Fourteen days after the operation, the total tumor volume of the LQ + MWA group was smaller than that of the LQ group and the MWA group (p < 0.05). The survival time of the LQ + MWA group was significantly longer than that of the MWA and LQ groups (p < 0.01). Heat shock protein 70 (HSP70), hypoxia inducible factor-1 α (HIF-1 α), vascular endothelial growth factor (VEGF), tumor microvessel density (MVD) were lower in the LQ + MWA group than the MWA and LQ groups at 12 h, on days 3 and 7. At hour 12 and on days 3 and 7, HSP70 mRNA and HIF-1α mRNA expression of MWA group were significantly higher than that of the LQ and LQ + MWA groups (p < 0.001). At 12 h, and on days 3 and 7, apoptotic rate of tumor cells in LQ + MWA group was higher than that of the MWA and LQ groups (p < 0.05). At 12 h and on days 3, 7 and 14, the proliferation index of tumor cells in residual tumor in LQ + MWA group was lower than that in the MWA and LQ groups (p < 0.05). CONCLUSION: Preoperative infusion of LQ can significantly enhance the MWA effects of liver VX2 tumor, inhibit the excessive proliferation of residual tumor and angiogenesis, and decrease metastasis and prolong the survival period of experimental animals.
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Liposomas , Neoplasias Hepáticas , Animales , Conejos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Microondas/uso terapéutico , Quercetina/farmacología , Quercetina/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: The present study aimed to evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) followed by apatinib in treating hepatocellular carcinoma (HCC) patients with Barcelona Clinic Liver Cancer (BCLC) stage C. METHODS: Totally, 110 HCC patients with BCLC stage C treated with DEB-TACE followed by apatinib were consecutively enrolled. Treatment response (including complete response rate (CR), objective response rate (ORR) and disease control rate (DCR)), survival data (progression-free survival (PFS), overall survival (OS)), and adverse events were documented during the follow-up. RESULTS: CR, ORR and DCR were 25.5%, 77.2% and 79.1% at 3 months, then were 29.1%, 59.1% and 71.0% at 6 months, respectively. Regarding survival, median PFS (95%CI) was 6.3 (5.0-7.7) months, meanwhile 1-year and 2-year PFS were 19.8% and 3.3%, respectively; median OS (95%CI) was 16.9 (10.2-23.7) months, then 1-year, 2-year and 3-year OS were 66.5%, 34.7% and 14.2%, respectively. Further subgroup analysis indicated that nodule size, Child-Pugh stage, Eastern Cooperative Oncology Group performance status score and level of portal vein invasion were negatively correlated with PFS or OS, which were further validated by univariate and multivariate Cox's regression analysis. Most adverse events by DEB-TACE and apatinib treatment were mild and well-tolerable. CONCLUSION: DEB-TACE followed by apatinib is effective and safe in treating BCLC stage C HCC patients, indicating its role as an acceptable option in HCC management.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Humanos , Neoplasias Hepáticas/patología , Piridinas/uso terapéuticoRESUMEN
To date, little attempt has been made to develop new treatments for Helicobacter pylori (H. pylori), although the community is aware of the shortage of treatments for H. pylori. In this study, we developed a 192-tandem-microwell-based high-throughput assay for ammonia that is a known virulence factor of H. pylori and a product of urease. We could identify few drugs, that is, panobinostat, dacinostat, ebselen, captan, and disulfiram, to potently inhibit the activity of ureases from bacterial or plant species. These inhibitors suppress the activity of urease via substrate-competitive or covalent-allosteric mechanism, but all except captan prevent the antibiotic-resistant H. pylori strain from killing human gastric cells, with a more pronounced effect than acetohydroxamic acid, a well-known urease inhibitor and clinically used drug for the treatment of bacterial infection. This study offers several bases for the development of new treatments for urease-containing pathogens and to study the mechanism responsible for the regulation of urease activity.
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Antibacterianos/química , Proteínas Bacterianas/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Infecciones por Helicobacter , Helicobacter pylori , Ureasa/antagonistas & inhibidores , Reposicionamiento de Medicamentos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/enzimología , HumanosRESUMEN
PURPOSE: The present study aimed to assess the prevalence of vascular lake (VL), its associated factors and correlation with prognosis in hepatocellular carcinoma (HCC) patients treated with drug-eluting bead transarterial chemoembolization (DEB-TACE). PATIENTS AND METHODS: A total of 286 primary HCC patients (with 384 treated nodules) receiving DEB-TACE treatment were recruited, and their clinical characteristics were documented. The occurrence of VL was recorded, and treatment responses were assessed according to the modified response evaluation criteria in solid tumor (mRECIST).In terms of treatment response, the total response status (including CR, PR, SD and PD), objective response rate (ORR) and disease control rate (DCR) were elevated in VL patients compared to non-VL patients as well as in VL nodules compared to non-VL nodules. Liver function indexes and adverse events were assessed. Progression-free survival (PFS) and overall survival (OS) were evaluated with the last follow-up date of March 2020. RESULTS: The patient-based and nodule-based VL occurrence rates were 17.1% and 16.4%, respectively. Larger tumor size, pseudocapsules and smaller bead size were independently associated with VL occurrence. PFS and OS were more prolonged in VL patients than in non-VL patients, and VL independently correlated with better PFS and OS. For liver function, the liver function indexes before and after DEB-TACE were of no difference between VL patients and non-VL patients. Additionally, the incidences of adverse events were similar between VL patients and non-VL patients. CONCLUSION: VL occurs in 17.1% of HCC patients treated with DEB-TACE, and it is correlated with larger tumor size, pseudocapsule, smaller bead size, more favorable treatment response and better survival.
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We retrospectively analyzed 17 patients with esophageal stent who underwent cervical esophageal and/or hypopharyngeal stenosis after total laryngectomy (TL) from January 2014 to January 2018. The success rate of stent implantation was 100%. Dysphagia in 16 patients improved to class 0 or 1 (16/17, 94.12%) after stent implantation and in 1 patient was improved to class 2 (1/17, 5.88%). Two patients died of tumor progression at 7 months and 11 months after stent implantation, respectively, but both could eat semi-solid/solid food before death. Dysphagia was resolved in the remaining 15 patients, and there was no recurrence of dysphagia including feeding obstruction during follow-up. Therefore, this case series concludes that the esophageal stent position after TL can be much higher than that of patients with normal pharyngeal structures. Esophageal stent implantation is a feasible and effective treatment for patients with laryngopharyngeal/esophageal stenosis following TL.
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Trastornos de Deglución , Neoplasias Esofágicas , Constricción Patológica/cirugía , Trastornos de Deglución/etiología , Trastornos de Deglución/cirugía , Humanos , Laringectomía/efectos adversos , Recurrencia Local de Neoplasia/etiología , Cuidados Paliativos , Estudios Retrospectivos , Stents/efectos adversos , Resultado del TratamientoRESUMEN
China's rapid urbanization process has accentuated the disparity between the demand for and supply of its park recreational services. Estimations of park use and an understanding of the factors that influence it are critical for increasing these services. However, the data traditionally used to quantify park use are often subjective as well as costly and laborious to procure. This paper assessed the use of parks through an analysis of check-in data obtained from the Weibo social media platform for 13,759 parks located in all 287 cities at prefecture level and above across China. We investigated how park attributes, accessibility, and the socioeconomic environment affected the number and density of park check-ins. We used multiple linear regression models to analyze the factors influencing check-ins for park visits. The results showed that in all the cities, the influence of external factors on the number and density of check-in visits, notably the densities of points of interest (POIs) and bus stops around the parks was significantly positive, with the density of POIs being the most influential factor. Conversely, park attributes, which included the park service area and the landscape shape index (LSI), negatively influenced park use. The density of POIs and bus stops located around the park positively influenced the density of the recreational use of urban parks in cities within all administrative tiers, whereas the impact of park service areas was negative in all of them. Finally, the factors with the greatest influence varied according to the administrative tiers of the cities. These findings provide valuable inputs for increasing the efficiency of park use and improving recreational services according to the characteristics of different cities.
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BACKGROUND: UK-2A is an antifungal antibiotic produced by Streptomyces sp. 517-02. Derivatization of its picolinamide OH to form the isobutyryl acetal led to the discovery of fenpicoxamid (InatreqTM active), which is currently under development as a fungicide by Dow AgroSciences LLC. This paper documents efforts to achieve additional efficacy enhancements through semi-synthetic modification of the benzyl substituent of the UK-2A macrocycle. RESULTS: Of 34 analogs prepared, the most active had mitochondrial electron transport IC50 values 1.5- to 3.7-fold higher than UK-2A (IC50 0.86 nM). The cyclohexyl analog (38, IC50 1.23 nM) was the most intrinsically active derivative, and inhibited in vitro growth of Zymoseptoria tritici (EC50 2.8 ppb) and Leptosphaeria nodorum (EC50 6.2 ppb) more strongly than UK-2A (EC50 5.3 and 11.3 ppb for Z. tritici and L. nodorum, respectively). Heterocyclic ring systems and polar linker functionalities resulted in substantial activity loss. Several analogs (20, 22, 23, 24, 36 and 38) translated Z. tritici in vitro growth inhibition activity to in planta disease control more effectively than did UK-2A, with log D being a key factor in this regard. CONCLUSIONS: UK-2A is amenable to further modification at the benzyl position on the macrocycle, which provides opportunities for manipulation of physical properties while retaining strong intrinsic and antifungal activity. © 2019 Society of Chemical Industry.
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Ascomicetos/efectos de los fármacos , Fungicidas Industriales/síntesis química , Ustilago/efectos de los fármacos , Complejo III de Transporte de Electrones/antagonistas & inhibidores , Fungicidas Industriales/química , Fungicidas Industriales/farmacología , Concentración 50 Inhibidora , Lactonas/síntesis química , Lactonas/química , Lactonas/farmacología , Mitocondrias , Piridinas/síntesis química , Piridinas/química , Piridinas/farmacología , Relación Estructura-Actividad , Triticum/microbiologíaRESUMEN
Significant differences in urban greening have occurred in Chinese cities, accompanied by China's rapid urbanization. However, there are relatively few studies on the spatial differentiation of urban greening in China at the city level. In addition, there is no unanimous conclusion on the main factors influencing the spatial differentiation of urban greening. Based on 2014 emission inventory data from 289 cities, the spatial differentiation pattern and spatial correlation characteristics of the urban green space ratio, urban green coverage rate, and public green area per capita were calculated and analyzed using global and local Moran's I. We then used ordinary least squares, spatial error model, spatial autoregression, and geographically weighted regression to quantify the impact and spatial variations of China's economy on urban greening. The results showed (1) a significant spatial dependence and heterogeneity existed in urban greening values, and the patterns showed influences of both the stage of economic development and spatial agglomeration; (2) regression models revealed per capita GDP had a positive effect on the urban green space ratio and public green area per capita while the urbanization rate, secondary industry, urban land, and population density had opposite effects on these two greening indexes; and (3) geographically weighted regression revealed per capita GDP had a greater influence on urban greening in the northwestern region than in the southeastern region. The study could constitute a valuable reference for mid-to-long-term green space planning policy in diverse parts of China and could further assist in coordinating the development of urban greening and economic growth.
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Conservación de los Recursos Naturales/estadística & datos numéricos , Desarrollo Económico , Monitoreo del Ambiente , Urbanización/tendencias , China , Ciudades , Ambiente , Industrias , Densidad de Población , Regresión Espacial , Población UrbanaRESUMEN
Access to adequate anatomical specimens can be an important aspect in learning the anatomy of domestic animals. In this study, the authors utilized a structured light scanner and fused deposition modeling (FDM) printer to produce highly accurate animal skeletal models. First, various components of the bovine skeleton, including the femur, the fifth rib, and the sixth cervical (C6) vertebra were used to produce digital models. These were then used to produce 1:1 scale physical models with the FDM printer. The anatomical features of the digital models and three-dimensional (3D) printed models were then compared with those of the original skeletal specimens. The results of this study demonstrated that both digital and physical scale models of animal skeletal components could be rapidly produced using 3D printing technology. In terms of accuracy between models and original specimens, the standard deviations of the femur and the fifth rib measurements were 0.0351 and 0.0572, respectively. All of the features except the nutrient foramina on the original bone specimens could be identified in the digital and 3D printed models. Moreover, the 3D printed models could serve as a viable alternative to original bone specimens when used in anatomy education, as determined from student surveys. This study demonstrated an important example of reproducing bone models to be used in anatomy education and veterinary clinical training. Anat Sci Educ 11: 73-80. © 2017 American Association of Anatomists.
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Anatomía/educación , Alternativas al Uso de Animales/métodos , Educación en Veterinaria/métodos , Imagenología Tridimensional/métodos , Modelos Anatómicos , Animales , Animales Domésticos/anatomía & histología , Huesos/anatomía & histología , Bovinos , Humanos , Impresión Tridimensional , Estudiantes de Medicina/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
Imprinting disorder during somatic cell nuclear transfer usually leads to the abnormality of cloned animals and low cloning efficiency. However, little is known about the role of donor cell imprinting in the development of cloned embryos. Here, we demonstrated that the imprinting (H19/Igf2) in porcine fetus fibroblasts derived from the morphologically abnormal cloned fetuses (the abnormal imprinting group) was more hypomethylated, and accordingly, significantly higher H19 transcription and lower Igf2 expression occurred in comparison with those in fibroblasts derived from morphologically normal cloned fetuses (the normal imprinting group) or donor fetus fibroblasts (the control group). When these fibroblasts were used as donor cells, the abnormal imprinting group displayed an even lower imprinting methylation level, in correspondence to the significantly downregulated expression of Dnmt1, Dnmt3a and Zfp57, and a markedly reduced blastocyst rate, while the normal imprinting group took on the similar patterns of imprinting, gene expression and embryo development to the control group. When 5-aza-dC was applied to reduce the fibroblasts imprinting methylation level in the normal imprinting group, cloned embryos displayed the more severely impaired imprinting and significantly lower blastocyst rate. While the upregulated H19 transcription in the abnormal imprinting group was knocked down, the imprinting statuses were partly rescued, and the cleavage and blastocyst rates significantly increased in cloned embryos. In all, donor cell imprinting disorder reduced the developmental efficiency of cloned embryos. This work provides a new insight into understanding the molecular mechanism of donor cells regulating the cloned embryo development.
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In this study, the indium composition x as well as the anisotropically biaxial strain in non-polar a-plane In x Ga1-x N on GaN is studied by X-ray diffraction (XRD) analysis. In accordance with XRD reciprocal lattice space mapping, with increasing indium composition, the maximum of the In x Ga1-x N reciprocal lattice points progressively shifts from a fully compressive strained to a fully relaxed position, then to reversed tensile strained. To fully understand the strain in the ternary alloy layers, it is helpful to grow high-quality device structures using a-plane nitrides. As the layer thickness increases, the strain of In x Ga1-x N layer releases through surface roughening and the 3D growth-mode.
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Low development of somatic cell nuclear transfer embryos could be due to the incomplete DNA methylation reprogramming, and Dnmt1s existing in donor cells may be one cause of this disrupted DNA methylation reprogramming. However, the reprogramming pattern of Dnmt1s and its effect on DNA methylation reprogramming in cloned embryos remain poorly understood. Here, we displayed that along with the significantly higher Dnmt1 expression at the zygotic gene activation stage of cloned embryos, genomic methylation level was markedly upregulated, and the arrested rate was significantly higher compared with their in vitro fertilization counterparts. Then, we demonstrated that Dnmt1s, not Dnmt1o, methylation and expression levels in cloned embryos were significantly higher from the 1-cell to 4-cell stage but markedly lower at the blastocyst stage. When Dnmt1s in donor cells was appropriately removed, more cloned embryos passed through the zygotic gene activation stage and the blastocyst rate significantly increased. Furthermore, Dnmt1s knockdown significantly improved itself and genomic methylation reconstruction in cloned embryos. Finally, we found that Dnmt1s removal significantly promoted the demethylation and expression of pluripotent genes in cloned embryos. Taken together, these data suggest that Dnmt1s in donor cells is a critical barrier to somatic cell nuclear transfer mediated DNA methylation reprogramming, impairing the development of cloned embryos.
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ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Metilación de ADN , Técnicas de Transferencia Nuclear , Animales , Reprogramación Celular , Clonación de Organismos , ADN (Citosina-5-)-Metiltransferasa 1/genética , Epigénesis Genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Porcinos , Activación TranscripcionalRESUMEN
Urban green spaces encourage outdoor activity and social communication that contribute to the health of local residents. Examining the relationship between the use of urban green spaces and factors influencing their utilization can provide essential references for green space site selection in urban planning. In contrast to previous studies that focused on internal factors, this study highlights the external factors (traffic convenience, population density and commercial facilities) contributing to the use of urban green spaces. We conducted a spatiotemporal analysis of the distribution of visitors in 208 selected green spaces in central Beijing. We examined the relationship between the spatial pattern of visitor distribution within urban green spaces and external factors, using the Gini coefficient, kernel density estimation, and geographical detectors. The results of the study were as follows. The spatial distribution of visitors within central Beijing's green spaces was concentrated, forming different agglomerations. The three examined external factors are all associated with the use of green spaces. Among them, commercial facilities are the important external factor associated with the use of green spaces. For the selection of sites for urban green spaces, we recommend consideration of external factors in order to balance urban green space utilization.
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Planificación de Ciudades , Parques Recreativos/estadística & datos numéricos , Beijing , HumanosRESUMEN
Glutamine and tyrosine-based amino acid conjugates of monocarboxylate transporter types 1 and 2 inhibitors (MCT1/2) were designed, synthesized and evaluated for their potency in blocking the proliferation of a human B lymphoma cell line that expresses the transporters Asct2, LAT1 and MCT1. Appropriate placement of an amino acid transporter recognition element was shown to augment anti-tumour efficacy vs. Raji cells. Amino acid conjugation also improves the pharmacodynamic properties of experimental MCT1/2 inhibitors.