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1.
Sci Rep ; 14(1): 8671, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622162

RESUMO

This study aimed to establish an astaxanthin-rich strain of the calanoid copepod Pseudodiaptomus annandalei, through selective breeding based on RGB (red, green and blue) value, a parameter indicating color intensity. We evaluated the RGB value frequency distributions of the copepod populations, and selected individuals with the highest 10% and the lowest 10% RGB value over six generations. The RGB value, nauplii production, clutch interval and clutch number were assessed, and the genetic gain was calculated across generations (G0-G5). Two strains of copepods were selected and defined as dark body copepod strain (DBS) and light body copepod strain (LBS) at the end of experiment. Results revealed significantly lower RGB values (male: 121.5 ± 14.1; female: 108.8 ± 15) in the G5 DBS population compared to the G0 (male: 163.9 ± 13.1; female: 162.2 ± 14.6), with higher genetic gains of RGB values during G0 to G2. While DBS females exhibited longer clutch intervals in the G3 and G4, there was no significant difference in nauplii production between the two strains across all generations. Significantly higher astaxanthin content was found in the DBS copepods (0.04 µg/ ind.) compared to the LBS copepods (0.01 µg/ ind.) and the non-selective copepods (0.02 µg/ ind.) 20 months post selective breeding, validating the stability of the desired trait in the DBS strain. This study successfully established an astaxanthin-rich strain of P. annandalei, which provides implications for enhancing marine and brackish larviculture production.


Assuntos
Copépodes , Animais , Feminino , Masculino , Copépodes/genética , Xantofilas
2.
Indian J Ophthalmol ; 72(Suppl 3): S415-S422, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324629

RESUMO

PURPOSE: In this study, we examined the current status of myopia among primary and secondary school children in northeastern Sichuan to analyze the factors connected to myopia and provide data support and a theoretical foundation for the prevention and control of myopia. METHODS: Using a cross-sectional study and a comprehensive sampling survey, 34,138 students aged 5-19 years were screened for refraction in 22 primary and secondary schools in Langzhong, and 4000 behavioral questionnaires were delivered at random. After evaluation and rational problem-solving, a total of 3764 valid questionnaires were obtained. SPSS 23.0 statistical software was used for data analysis. RESULTS: The percentage of myopia among primary and secondary school students in Langzhong was 65.61%, with female students having a higher rate than male students ( P < 0.05); 52.81% of primary school students, 86.26% of secondary school students, and 88.17% of high school students had myopia. The incidence of myopia detection increased with school age ( P < 0.001), indicating a correlation between age and myopia prevalence. The prevalence of myopia was mainly low (40.53%) and moderate myopia (19.89%). The prevalence of high myopia (5.19%) was relatively high. The prevalence of myopia among female students (5.54%) was greater than that in male students ( P < 0.05) and increased with age ( P < 0.001). The proportion of students who wore eyeglasses was 24.36%, with a larger proportion of female students (25.93%) than male students (22.61%) ( P < 0.001). In addition, the rate of eyeglass use increased with school age ( P < 0.001). A logistic regression analysis revealed that higher grade point averages, female gender, and long-term usage of electronic items were risk factors for myopia. The results of the questionnaire survey revealed that students in this region were under immense pressure to perform well academically, spent a lot of time engaged in near-work activities, and had a low rate of myopia awareness; 24.43% of the students had not had a vision examination in the previous year, indicating that parents did not pay sufficient attention to eye health. CONCLUSION: The incidence of myopia among children and teenagers is high in Northeast Sichuan, and the outlook for addressing the problem is bleak. Therefore, it is critical to improve vision monitoring and eye health education.

3.
Epigenomics ; 16(2): 127-136, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38126127

RESUMO

The authors highlight an area of research that focuses on the establishment of genomic imprints: how the female and male germlines set up opposite instructions for imprinted genes in the maternally and paternally inherited chromosomes. Mouse genetics studies have solidified the role of transcription across the germline differentially methylated regions in the establishment of maternal genomic imprinting. One work now reveals that such transcription is also important in paternal imprinting establishment. This allows the authors to propose a unifying mechanism, in the form of transcription across germline differentially methylated regions, that specifies DNA methylation imprint establishment. Differences in the timing, genomic location and nature of such transcription events in the male versus female germlines in turn explain the difference between paternal and maternal imprints.


Assuntos
Metilação de DNA , Impressão Genômica , Animais , Camundongos , Células Germinativas
4.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(6): 1074-1081, 2023 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-38101792

RESUMO

OBJECTIVE: To study epidemiological characteristics and hospitalization costs of female inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing. METHODS: A retrospective study was conducted to analyze electronic hospitalization summary reports of female inpatients with AECOPD in Beijing from 2013 to 2020. Clinical characteristics (age distribution and comorbidities), epidemiological characteristics (temporal and spatial distribution characteristics), hospi-talization times and costs of patients were described. RESULTS: A total of 57 911 subjects in 166 hospitals were included in this study, with a mean age of (78.84±8.59) years and the highest number of patients aged 80-89 years (49.06%), followed by patients aged 70-79 years (31.08%), and the lowest number of patients under 50 years (0.41%). The proportions of patients with coronary heart disease, hypertension and heart failure were 30.60%, 30.52% and 26.54% respectively. The median number of daily hospitalizations during the study period was 18 (IQR: 16). The number of daily hospitalizations for AECOPD showed an overall growth trend over the eight years from 2013 to 2020, starting to increase significantly in 2015 and continuing to increase until 2019, then followed by a decline in 2020. The proportion of inpatient admissions was higher in winter and spring (54.09%) than that in summer and autumn (45.91%). The top three districts in terms of the proportion of total inpatient admissions were Xicheng district (14.18%), Chaoyang district (14.12%) and Fengtai district (13.47%). The density of inpatients was relatively high in the western regions, central urban areas and northeastern regions of the city, while the density of inpatients was relatively low in the near suburbs. The median number of hospital days for female patients with AECOPD was 12 days, and the median hospital costs was CNY 20 648.37. Patients from urban areas had longer hospitalization times and higher hospitalization costs than those from suburban areas (P < 0.001). Western medicine expenses accounted for the largest proportion of total hospital expenses (33.32%). During the study period, hospitalization costs exhibited an overall pattern of initial growth, followed by subsequent decline, eventually stabilizing. The differences in hospitalization costs among the patients with different comorbidities were significant. CONCLUSION: Female hospitalized patients with AECOPD in Beijing were older than 70 years, often complicated by cardiovascular disease. AECOPD occurred mainly in winter and spring, with regional differences. The hospitalization costs were closely associated with the patients' age, comorbidities, and the geographicical region.


Assuntos
Pacientes Internados , Doença Pulmonar Obstrutiva Crônica , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Pequim , Estudos Retrospectivos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Hospitalização
5.
Phys Rev Lett ; 131(16): 166703, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37925723

RESUMO

Finding tunable van der Waals (vdW) ferromagnets that operate at above room temperature is an important research focus in physics and materials science. Most vdW magnets are only intrinsically magnetic far below room temperature and magnetism with square-shaped hysteresis at room temperature has yet to be observed. Here, we report magnetism in a quasi-2D magnet Cr_{1.2}Te_{2} observed at room temperature (290 K). This magnetism was tuned via a protonic gate with an electron doping concentration up to 3.8×10^{21} cm^{-3}. We observed nonmonotonic evolutions in both coercivity and anomalous Hall resistivity. Under increased electron doping, the coercivities and anomalous Hall effects (AHEs) vanished, indicating a doping-induced magnetic phase transition. This occurred up to room temperature. DFT calculations showed the formation of an antiferromagnetic (AFM) phase caused by the intercalation of protons which induced significant electron doping in the Cr_{1.2}Te_{2}. The tunability of the magnetic properties and phase in room temperature magnetic vdW Cr_{1.2}Te_{2} is a significant step towards practical spintronic devices.

6.
Sci Adv ; 9(36): eadi2050, 2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37672574

RESUMO

The insulator model explains the workings of the H19 and Igf2 imprinted domain in the soma, where insulation of the Igf2 promoter from its enhancers occurs by CTCF in the maternally inherited unmethylated chromosome but not the paternally inherited methylated allele. The molecular mechanism that targets paternal methylation imprint establishment to the imprinting control region (ICR) in the male germline is unknown. We tested the function of prospermatogonia-specific broad low-level transcription in this process using mouse genetics. Paternal imprint establishment was abnormal when transcription was stopped at the entry point to the ICR. The germline epimutation persisted into the paternal allele of the soma, resulting in reduced Igf2 in fetal organs and reduced fetal growth, consistent with the insulator model and insulin-like growth factor 2 (IGF2)'s role as fetal growth factor. These results collectively support the role of broad low-level transcription through the H19/Igf2 ICR in the establishment of its paternal methylation imprint in the male germ line, with implications for Silver-Russell syndrome.


Assuntos
Desenvolvimento Fetal , Processamento de Proteína Pós-Traducional , Animais , Camundongos , Metilação , Alelos , Fosforilação
7.
Ann Transplant ; 28: e939343, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37043447

RESUMO

BACKGROUND The aim of this study was to explore the evaluation and use of donor organs from donors with brain death caused by acute severe organophosphorus pesticides and provide a basis for the use of such donor organs. MATERIAL AND METHODS Seven cases of brain dead donors caused by acute organophosphorus pesticide poisoning from January 2014 to December 2018 in the hospital were collected, and a retrospective analysis was made of the donors' age, race, physiological and pathological changes, donor organ function changes and the organ use, liver or kidney function recovery, and complications of the recipients. The 18 recipients were followed up until June 31, 2022. RESULTS We found that 71.42% of organ donors were male, and 71.42% of organ donors were under 50 years old. The main cause of death was respiratory failure caused by organophosphorus pesticide poisoning. The liver and kidney functions of 7 donors were damaged, and 3 livers could not be used due to severe functional damage, but the liver or kidney function of 18 recipients gradually recovered after transplantation. Delayed recovery of graft function occurred after transplantation accounted for 21.43%, and the grafts had good short-term to medium-term performance. CONCLUSIONS Although the function of organs from donor with brain death due to acute severe organophosphorus pesticide poisoning is seriously damaged, most of the organs can still be used for transplantation. Individualized functional maintenance according to the situation of donors is conducive to improving the quality of organs.


Assuntos
Transplante de Fígado , Praguicidas , Venenos , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Compostos Organofosforados , Praguicidas/toxicidade , Estudos Retrospectivos , Morte Encefálica , Doadores de Tecidos , Sobrevivência de Enxerto
8.
Materials (Basel) ; 15(22)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36431562

RESUMO

A new S600E sorbite stainless steel (SS), which performs outstanding mechanical properties, was introduced in a plate girder to enhance the resistant performance and durability. The resistance from the flange for S600E sorbite SS plate girders developing post-buckling capacity was investigated through numerical analyses, which included the material and geometrical nonlinearity. The value of distance between plastic hinges performed significant effects on resistance from flange. There was a certain distribution range of the flange plastic hinge. Hence, it was difficult to determine the value of distance between plastic hinges accurately based merely on the failure behavior. Considering the theoretical basis of EN 1993-1-4: 2006+A1, the new methods to obtain resistance from the flange and determine the value of distance between the plastic hinges were proposed to avoid the aforementioned error. The parametric study was conducted to investigate the effect of key parameters on the resistance from the flange. To take the above effect into account, a correction factor was proposed for the design equation in EN 1993-1-4: 2006+A1 to predict the distance between flange plastic hinges accurately. The comparison was conducted to validate the accuracy of the proposed equations. The results indicated that the new modified equation could be used to predict the resistance from the flange of the S600E sorbite SS plate girder more accurately.

9.
PLoS Genet ; 17(11): e1009908, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34793451

RESUMO

EHMT2 is the main euchromatic H3K9 methyltransferase. Embryos with zygotic, or maternal mutation in the Ehmt2 gene exhibit variable developmental delay. To understand how EHMT2 prevents variable developmental delay we performed RNA sequencing of mutant and somite stage-matched normal embryos at 8.5-9.5 days of gestation. Using four-way comparisons between delayed and normal embryos we clarified what it takes to be normal and what it takes to develop. We identified differentially expressed genes, for example Hox genes that simply reflected the difference in developmental progression of wild type and the delayed mutant uterus-mate embryos. By comparing wild type and zygotic mutant embryos along the same developmental window we detected a role of EHMT2 in suppressing variation in the transcriptional switches. We identified transcription changes where precise switching during development occurred only in the normal but not in the mutant embryo. At the 6-somite stage, gastrulation-specific genes were not precisely switched off in the Ehmt2-/- zygotic mutant embryos, while genes involved in organ growth, connective tissue development, striated muscle development, muscle differentiation, and cartilage development were not precisely switched on. The Ehmt2mat-/+ maternal mutant embryos displayed high transcriptional variation consistent with their variable survival. Variable derepression of transcripts occurred dominantly in the maternally inherited allele. Transcription was normal in the parental haploinsufficient wild type embryos despite their delay, consistent with their good prospects. Global profiling of transposable elements revealed EHMT2 targeted DNA methylation and suppression at LTR repeats, mostly ERVKs. In Ehmt2-/- embryos, transcription over very long distances initiated from such misregulated 'driver' ERVK repeats, encompassing a multitude of misexpressed 'passenger' repeats. In summary, EHMT2 reduced transcriptional variation of developmental switch genes and developmentally switching repeat elements at the six-somite stage embryos. These findings establish EHMT2 as a suppressor of transcriptional and developmental variation at the transition between gastrulation and organ specification.


Assuntos
Embrião de Mamíferos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Histona-Lisina N-Metiltransferase/metabolismo , Transcrição Gênica , Animais , Ilhas de CpG , Metilação de DNA , Feminino , Haploinsuficiência , Histona-Lisina N-Metiltransferase/genética , Camundongos , Transcriptoma
11.
Epigenomics ; 13(16): 1299-1314, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34519223

RESUMO

Aim: Paternal allele-specific expression of noncanonical imprinted genes in the extraembryonic lineages depends on an H3K27me3-based imprint in the oocyte, which is not a lasting mark. We hypothesized that EHMT2, the main euchromatic H3K9 dimethyltransferase, also has a role in controlling noncanonical imprinting. Methods: We carried out allele-specific total RNA-seq analysis in the ectoplacental cone of somite-matched 8.5 days post coitum embryos using reciprocal mouse crosses. Results: We found that the maternal allele of noncanonical imprinted genes was derepressed from its ERVK promoter in the Ehmt2-/- ectoplacental cone. In Ehmt2-/- embryos, loss of DNA methylation accompanied biallelic derepression of the ERVK promoters. Canonical imprinting and imprinted X chromosome inactivation were generally undisturbed. Conclusion: EHMT2 is essential for repressing the maternal allele in noncanonical imprinting.


Assuntos
Regulação da Expressão Gênica , Impressão Genômica , Histona-Lisina N-Metiltransferase/metabolismo , Animais , Biomarcadores , Metilação de DNA , Feminino , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Placenta/metabolismo , Gravidez , Regiões Promotoras Genéticas , Espermatozoides , Sequenciamento Completo do Genoma
12.
Nucleic Acids Res ; 49(13): 7554-7570, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34197606

RESUMO

Polo-like kinase 1 (PLK1) is a master kinase that regulates cell cycle progression. How its enzymatic activity is regulated in response to DNA damage is not fully understood. We show that PLK1 is enriched at double strand breaks (DSBs) within seconds of UV laser irradiation in a PARP-1-dependent manner and then disperses within 10 min in a PARG-dependent manner. Poly(ADP-)ribose (PAR) chains directly bind to PLK1 in vitro and inhibit its enzymatic activity. CHK1-mediated PLK1 phosphorylation at S137 prevents its binding to PAR and recruitment to DSBs but ensures PLK1 phosphorylation at T210 and its enzymatic activity toward RAD51 at S14. This subsequent phosphorylation event at S14 primes RAD51 for CHK1-mediated phosphorylation at T309, which is essential for full RAD51 activation. This CHK1-PLK1-RAD51 axis ultimately promotes homologous recombination (HR)-mediated repair and ensures chromosome stability and cellular radiosensitivity. These findings provide biological insight for combined cancer therapy using inhibitors of PARG and CHK1.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Quinase 1 do Ponto de Checagem/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Reparo de DNA por Recombinação , Proteínas de Ciclo Celular/antagonistas & inibidores , Linhagem Celular , Quebras de DNA de Cadeia Dupla , Glicosídeo Hidrolases , Humanos , Fosforilação , Poli Adenosina Difosfato Ribose/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Rad51 Recombinase/metabolismo , Raios Ultravioleta , Quinase 1 Polo-Like
13.
BMC Infect Dis ; 21(1): 524, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088268

RESUMO

BACKGROUND: With pandemic of coronavirus disease 2019 (COVID-19), human coronaviruses (HCoVs) have recently attached worldwide attention as essential pathogens in respiratory infection. HCoV-229E has been described as a rare cause of lower respiratory infection in immunocompetent adults. CASE PRESENTATION: We reported a 72-year-old man infected by HCoV-229E with rapid progression to acute respiratory distress syndrome, in conjunction with new onset atrial fibrillation, intensive care unit acquired weakness, and recurrent hospital acquired pneumonia. Clinical and radiological data were continuously collected. The absolute number of peripheral T cells and the level of complement components diminished initially and recovered after 2 months. The patient was successfully treated under intensive support care and discharged from the hospital after 3 months and followed. CONCLUSION: HCoV-229E might an essential causative agent of pulmonary inflammation and extensive lung damage. Supportive treatment was essential to HCoVs infection on account of a long duration of immunological recovery in critical HCoV-229E infection.


Assuntos
Resfriado Comum/diagnóstico , Coronavirus Humano 229E , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Idoso , Antibacterianos/uso terapêutico , Líquido da Lavagem Broncoalveolar/virologia , Resfriado Comum/complicações , Resfriado Comum/virologia , Infecções por Coronavirus/complicações , Diabetes Mellitus , Pneumonia Associada a Assistência à Saúde/complicações , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pneumonia Viral/tratamento farmacológico
14.
BMC Med Imaging ; 21(1): 33, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33618703

RESUMO

BACKGROUND: This study aims to compare the difference of the brain changes of glucose metabolism between temporal lobe epilepsy patients (TLE) with major depressive disorder and temporal TLE without major depressive disorder. METHODS: A total of 24 TLE patients, who met the inclusion criteria of our hospital, were enrolled in this study. They were divided into a TLE with depression group (n = 11) and a TLE without depression group (n = 13), according to the results of the HAMD-24 Scale. Two groups patients were examined using 18F-FDG PET brain imaging. RESULTS: The low metabolic regions of the TLE with depression group were mainly found in the left frontal lobe, temporal lobe and fusiform gyrus, while the high metabolic regions of the TLE with depression group were mainly located in the right frontal lobe, visual joint cortex and superior posterior cingulate cortex. Both of the TLE groups had high metabolic compensation in the non-epileptic area during the interictal period. CONCLUSIONS: There is an uptake difference of 18F-FDG between TLE patients with depression and TLE patients without depression in multiple encephalic regions.


Assuntos
Encéfalo/metabolismo , Transtorno Depressivo Maior/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Glucose/metabolismo , Adulto , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/complicações , Eletroencefalografia , Epilepsia do Lobo Temporal/psicologia , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Lobo Temporal/metabolismo
15.
J Thorac Dis ; 13(1): 92-100, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33569189

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become a major public-health problem in China. Surfactant protein D (SP-D) is a very promising biomarker and therapeutic target for COPD. To assess whether baseline serum SP-D is associated with lung function decline and incident COPD. METHODS: This longitudinal study was initiated in 2009 in a community in Beijing. Data were collected on spirometry, and the baseline level of serum SP-D was measured in 772 non-COPD subjects aged 40-70 years old. In 2012, spirometry was repeated in 364 individuals, 37 of whom subjects had incident COPD. RESULTS: From 2009 to 2012, subjects with incident COPD had a more rapid decline in FEV1 (MD 98.27 vs. MD 43.41 mL) compared with those without COPD. There was no association between baseline serum SP-D and the COPD incidence. Smoking (OR =2.72; P=0.002) and age (OR =1.06; P=0.000) were risk factors for COPD. The rate of FEV1 decline varies widely in the general population, and the univariate analysis showed that baseline serum SP-D levels (R=-0.169; P=0.003), income level, home-road distance, and statin use were inversely correlated with the decline in FEV1. After multivariable analyses, only smoking was consistently associated with the decline in FEV1. CONCLUSIONS: There was no correlation between baseline serum SP-D levels and incident COPD in a general population. Smoking and age were major risk factors for COPD. The effect of serum SP-D levels on the decline in FEV1 needs further investigation.

16.
Cell Rep ; 34(6): 108729, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33567274

RESUMO

Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are imprinting disorders manifesting as aberrant fetal growth and severe postnatal-growth-related complications. Based on the insulator model, one-third of BWS cases and two-thirds of SRS cases are consistent with misexpression of insulin-like growth factor 2 (IGF2), an important facilitator of fetal growth. We propose that the IGF2-dependent BWS and SRS cases can be identified by prenatal diagnosis and can be prevented by prenatal intervention targeting IGF2. We test this hypothesis using our mouse models of IGF2-dependent BWS and SRS. We find that genetically normalizing IGF2 levels in a double rescue experiment corrects the fetal overgrowth phenotype in the BWS model and the growth retardation in the SRS model. In addition, we pharmacologically rescue the BWS growth phenotype by reducing IGF2 signaling during late gestation. This animal study encourages clinical investigations to target IGF2 for prenatal diagnosis and prenatal prevention in human BWS and SRS.


Assuntos
Síndrome de Beckwith-Wiedemann , Marcação de Genes , Fator de Crescimento Insulin-Like II , Diagnóstico Pré-Natal , Síndrome de Silver-Russell , Animais , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/embriologia , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/terapia , Modelos Animais de Doenças , Feminino , Humanos , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Camundongos , Gravidez , Síndrome de Silver-Russell/diagnóstico , Síndrome de Silver-Russell/embriologia , Síndrome de Silver-Russell/genética , Síndrome de Silver-Russell/terapia
17.
Sci Rep ; 10(1): 20636, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33244015

RESUMO

A battery of chromatin modifying enzymes play essential roles in remodeling the epigenome in the zygote and cleavage stage embryos, when the maternal genome is the sole contributor. Here we identify an exemption. DOT1L methylates lysine 79 in the globular domain of histone H3 (H3K79). Dot1l is an essential gene, as homozygous null mutant mouse embryos exhibit multiple developmental abnormalities and die before 11.5 days of gestation. To test if maternally deposited DOT1L is required for embryo development, we carried out a conditional Dot1l knockout in growing oocytes using the Zona pellucida 3-Cre (Zp3-Cre) transgenic mice. We found that the resulting maternal mutant Dot1lmat-/+ offspring displayed normal development and fertility, suggesting that the expression of the paternally inherited copy of Dot1l in the embryo is sufficient to support development. In addition, Dot1l maternal deletion did not affect the parental allele-specific expression of imprinted genes, indicating that DOT1L is not needed for imprint establishment in the oocyte or imprint protection in the zygote. In summary, uniquely and as opposed to other histone methyltransferases and histone marks, maternal DOT1L deposition and H3K79 methylation in the zygote and in the preimplantation stage embryo is dispensable for mouse development.


Assuntos
Histona-Lisina N-Metiltransferase/metabolismo , Animais , Blastocisto/metabolismo , Proliferação de Células/fisiologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/fisiologia , Histona Metiltransferases/metabolismo , Histonas/metabolismo , Lisina/metabolismo , Metilação , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Modelos Animais , Oócitos/metabolismo , Zigoto/metabolismo
18.
Phys Chem Chem Phys ; 22(28): 16236-16243, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32643728

RESUMO

Two-dimensional boron structures, due to their diverse properties, have attracted great attention because of their potential applications in nanoelectronic devices. A series of TiBn (2 ≤ n ≤ 13) monolayers are efficiently constructed through our motif based method and theoretically investigated through high-throughput first-principles calculations. The configurations are generated based on the motifs of boron dimeric/triangular/quadrilateral fragments and multi-coordinate titanium-centered boron molecular wheels. Besides previously reported TiB4 and TiB9 which were discovered by the global search method, we predict that high symmetry monolayer TiB7 (Cmmm), which is octa-coordinate titanium boride, is dynamically stable. The TiB7 monolayer is a BCS superconductor with a transition temperature Tc of up to 8.3 K. The motif based approach is proved to be efficient in searching stable structures with prior knowledge so that the potentially stable transition metal monolayers can be quickly constructed by using basic cluster motifs. As an efficient way of discovering materials, the method is easily extended to predict other types of materials which have common characteristic patterns in the structure.

19.
J Phys Chem A ; 124(22): 4506-4511, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32374598

RESUMO

The tunable properties of materials originate from variety of structures; however, it is still a challenge to give an accurate and fast evaluation of stabilities for screening numerous candidates. Herein, we propose an atom classification model to describe the multicomponent materials based on the structural recognition, in which the atoms are classified to estimate the total energies. Taking two-dimensional planar C1-xBx and C1-2x(BN)x as examples, we have found that the test error of total energies is about 3 meV per atom. Notably, the distributions of classified atoms demonstrate the evolution of configurations as a function of temperature, providing a clearer picture of phase transition. In addition, our method is universal, which can be flexibly extended to the bulk structures with more components.

20.
Bioorg Chem ; 94: 103346, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31645277

RESUMO

Many natural or synthetic chalcones have potential anti-tumor activity. Here, we synthesized two series of chalcone analogues containing a thieno[2,3-d]pyrimidin-2-yl group and evaluated for their cytotoxic activity towards cultured human lung cancer A549 and colorectal HCT-116 cells. Among them, compound 8d was the most cytotoxic against HCT-116 cells, with an IC50 value of 2.65 µM. Analyses of the phenotypic changes induced by this compound found a dose-dependent accumulation of HCT-116 cells in sub-G1 phase, indicating that compound 8d might induce apoptosis. Furthermore, we found that 8d triggered mitochondrial membrane potential depolarization, promoted reactive oxygen species formation in HCT-116 cells, and increased the percentage of early and late apoptotic cells. Finally, immunoblotting indicated that 8d increased PARP-1 and caspases 3, 7 and 9 cleavage. These data suggest that compound 8d induces apoptosis via the mitochondrial death pathway.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Chalconas/síntese química , Chalconas/farmacologia , Pirimidinas/química , Células A549 , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Chalconas/química , Células HCT116 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
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