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Mammalian interspecific hybrids provide unique advantages for mechanistic studies of speciation, gene expression regulation, and X chromosome inactivation (XCI) but are constrained by their limited natural resources. Previous artificially generated mammalian interspecific hybrid cells are usually tetraploids with unstable genomes and limited developmental abilities. Here, we report the generation of mouse-rat allodiploid embryonic stem cells (AdESCs) by fusing haploid ESCs of the two species. The AdESCs have a stable allodiploid genome and are capable of differentiating into all three germ layers and early-stage germ cells. Both the mouse and rat alleles have comparable contributions to the expression of most genes. We have proven AdESCs as a powerful tool to study the mechanisms regulating X chromosome inactivation and to identify X inactivation-escaping genes, as well as to efficiently identify genes regulating phenotypic differences between species. A similar method could be used to create hybrid AdESCs of other distantly related species.
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Fusão Celular/métodos , Quimera/genética , Células-Tronco Embrionárias/citologia , Células Híbridas , Camundongos , Ratos , Animais , Diferenciação Celular , Corpos Embrioides , Células-Tronco Embrionárias/metabolismo , Feminino , Haploidia , Masculino , Camundongos Endogâmicos , Ratos Endogâmicos F344 , Especificidade da Espécie , Inativação do Cromossomo XRESUMO
Pluripotency of embryonic stem cells (ESCs) can be functionally assessed according to the developmental potency. Tetraploid complementation, through which an entire organism is produced from the pluripotent donor cells, is taken as the most stringent test for pluripotency. It remains unclear whether ESCs of other species besides mice can pass this test. Here we show that the rat ESCs derived under 2i (two small molecule inhibitors) conditions at very early passages are able to produce fertile offspring by tetraploid complementation. However, they lose this capacity rapidly during culture due to a nearly complete loss of genomic imprinting. Our findings support that the naïve ground state pluripotency can be captured in rat ESCs but also point to the species-specific differences in its regulation and maintenance, which have implications for the derivation and application of naïve pluripotent stem cells in other species including human.
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Embrião de Mamíferos/citologia , Desenvolvimento Embrionário/fisiologia , Células-Tronco Embrionárias/citologia , Células-Tronco Pluripotentes/citologia , Animais , Diferenciação Celular , Células Cultivadas , Feminino , Teste de Complementação Genética , Camundongos , Ratos , Ratos Endogâmicos F344 , TetraploidiaRESUMO
Metalloproteinase 9 (MMP-9) is able to degrade collagen IV, an important component of blood-brain barrier (BBB). Expression of MMPs, especially MMP-9, correlates with BBB disruption during central nervous system inflammation. Propofol has been reported to have anti-inflammation effects. In this study, we investigated the effects of propofol on TNF-α-induced MMP-9 expression in human cerebral microvascular endothelial cells (hCMEC/D3 cells) and explored the underlying mechanisms. The hCMEC/D3 cells were treated with propofol (25 µM), followed by TNF-α (25 ng/mL). We showed that TNF-α treatment markedly increased MMP-9 expression and decreased collagen IV expression in hCMEC/D3 cells, which was blocked by pretreatment with propofol. TNF-α-induced downregulation of collagen IV was also reversed by MMP-9 knockdown with siRNA. We revealed that TNF-α upregulated MMP-9 expression in hCMEC/D3 cells through activation of Ca2+/CAMK II/ERK/NF-κB signaling pathway; co-treatment with inhibitors of CaMK II (KN93), ERK (LY3214996), NF-κB (PDTC) or Ca2+chelator (BAPTA-AM) abrogated the effect of TNF-α on MMP-9 expression. We further established an in vitro BBB model by co-culturing of hCMEC/D3 cells and human astrocytes for 6 days and measuring trans-endothelial electrical resistance (TEER) to reflect the BBB permeability. TNF-α treatment markedly decreased TEER value, which was attenuated by pretreatment with propofol (25 µM) or MMP-9 knockdown with siRNA. In conclusion, propofol inhibits TNF-α-induced MMP-9 expression in hCMEC/D3 cells via repressing the Ca2+/CAMKII/ERK/NF-κB signaling pathway. TNF-α-impaired BBB integrity could be reversed by propofol, and propofol attenuates the inhibitory effect of TNF-α on collagen IV.
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Células Endoteliais/efeitos dos fármacos , Metaloproteinase 9 da Matriz/genética , Microvasos/efeitos dos fármacos , Propofol/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Microvasos/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Three new sesquiterpenes, methyl 4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (1), methyl 2-hydroxy-4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (2), and methyl 2-hydroxy-6-(hydroxymethyl)-4-isopropyl-7-methoxynaphthalene-1-carboxylate (3), together with three known sesquiterpenes (4-6), were isolated from the stems of Nicotiana tabacum. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. The results showed that compounds 2, 3, and 5 exhibited high anti-TMV activity with inhibition rates of 33.6, 35.8, and 36.7%. Compounds 1-6 showed weak inhibitory activities against some tested human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7) with IC50 values in the range of 6.7-9.6 µM.
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Antineoplásicos Fitogênicos/farmacologia , Nicotiana/química , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Sesquiterpenos/químicaRESUMO
BACKGROUND The aim of this study was to investigate the correlation between Hector Battifora mesothelial-1 (HBME-1) expression and the clinical pathological characteristics and prognosis of osteosarcoma (OS). MATERIAL AND METHODS HBME-1 expression was assessed using immunohistochemistry in OS tissues (n=152), osteochondroma tissues (n=91), and normal bone tissues (n=74). We carried out a follow-up lasting 8-60 months to investigate HBME-1 expression and its correlations with the clinical pathological characteristics and prognosis of OS. RESULTS HBME-1 was highly expressed in OS tissues compared with osteochondroma tissues and normal bone tissues, and was highly expressed in osteochondroma tissues compared with normal bone tissues (all P<0.05). HBME-1 expression was correlated with clinical stages, postoperative recurrence, metastasis, and 5-year survival (all P<0.05). The area under the receiver operating characteristics curve of HBME-1 expression was 0.864, with sensitivity of 80.92%, specificity of 91.89%, and accuracy of 84.51%. The survival rate was lower in the HBME-1 positive expression group than the HBME-1 negative expression group (P<0.05). Clinical stages, metastasis, and HBME-1 expression were independent risk factors for the survival of patients with OS (all P<0.05). CONCLUSIONS HBME-1 expression was correlated with the occurrence and development of OS. HBME-1 positive expression was a risk factor for the prognosis of OS.
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Biomarcadores Tumorais/biossíntese , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Adolescente , Adulto , Criança , Transição Epitelial-Mesenquimal , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Osteocondroma/metabolismo , Osteocondroma/patologia , Prognóstico , Curva ROC , Fatores de RiscoRESUMO
BACKGROUND: The mechanism of cholesteryl ester transfer protein (CETP) in lipid metabolism is still unclear. Furthermore, the relationship of CETP and atherosclerosis (AS) has been controversial. As pigs are a good model for both lipid and AS research, we investigated the lipid metabolism of human CETP (hCETP) transgenic pigs and explored the mechanism of CETP in lipid modulation. METHODS: Plasmids expressing the hCETP gene were designed, successfully constructed, and transfected into porcine fetal fibroblasts by liposomes. Using somatic cell nuclear transfer technology and embryonic transfer, hCETP transgenic pigs were generated. After the DNA, RNA, and protein levels were identified, positive hCETP transgenic pigs were selected. Blood samples were collected at different ages to evaluate the phenotypes of biochemical markers, and the metabolomes of plasma samples were analyzed by liquid mass spectrometry. RESULTS: Eight positive hCETP transgenic pigs and five negative cloned pigs were generated by transgenic technology. Finally, five hCETP transgenic and five cloned pigs were grown healthily. After feeding with a normal diet, hCETP transgenic pigs compared with unmodified pigs had no significant differences in body weight, liver function, kidney function, or plasma ions, while total cholesterol and low-density lipoprotein were higher than in unmodified pigs, and high-density lipoprotein was significantly decreased. Metabolomics analysis showed that there were differences in metabolic components between hCETP transgenic pigs, cloned pigs, and unmodified pigs. CONCLUSIONS: In this study, we created hCETP transgenic pigs that could serve as an excellent model for lipid disorders and atherosclerosis.
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Aterosclerose/genética , Proteínas de Transferência de Ésteres de Colesterol/genética , Dislipidemias/genética , Sus scrofa/genética , Animais , Animais Geneticamente Modificados , Aterosclerose/etiologia , Colesterol/sangue , Colesterol/genética , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Modelos Animais de Doenças , Dislipidemias/etiologia , Feminino , Expressão Gênica , Humanos , Lipoproteínas LDL/genética , Lipoproteínas LDL/metabolismoRESUMO
Plant canopy pigment concentration is a critical variable for agricultural remote sensing due to its close relationship to leaf nitrogen content. The aims of this study were to: (1) compare the prediction performances on chlorophyll, chlorophyll-a and b, and carotenoid concentration in jujube leaf at canopy scale between partial least squares regression (PLSR) and support vector machine (SVM), (2) develop quantitative models to estimate pigment concentration in jujube canopy using hyperspectral data and provide theoretical and technical support for rapidly, non-destructive, less expensive and eco-friendly measuring the concentration. Results from correlation analysis showed that jujube canopy pigment concentration correlated strongly with hyperspectral data. What's more, the hyperspectral data was better correlated by chlorophyll and chlorophyll-a than chlorophyll-b and carotenoid. Results of independent samples tested in predicting performance indicated that both of the PLSR and SVM models could effectively estimate pigment concentration, however, with different prediction precisions. Additionally, the precision of SVM outperformed PLSR for predicting chlorophyll and carotenoid. Whereas chlorophyll-a and chlorophyll-b were better predicted using PLSR than SVM. Compared among all the pigments' prediction precisions with corresponding optimal inversion models showed that prediction precisions on chlorophyll, chlorophyll-a and carotenoid were superior to chlorophyll-b. The determination coefficients and residual prediction deviation from predicting chlorophyll, chlorophyll-a and carotenoid were higher than 0.8 and 2.0, respectively, while the mean relative error values were lower than 13%. And the corresponding values from predicting chlorophyll-b were 0.60%, 20.79% and 1.79% respectively.
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Ziziphus , Carotenoides , Clorofila , Clorofila A , Frutas , Análise dos Mínimos Quadrados , Modelos Teóricos , Pigmentação , Folhas de Planta , Análise Espectral , Máquina de Vetores de SuporteRESUMO
The precipitation of floating and sinking dust on leaves of plants is called as foliar dustfall. To monitor foliar dustfall, it will provide fundamental basis for environmental assessment and agricultural disaster evaluation of dust area. Therefore, the aim of this work to (1) study the effect of foliar dustfall content (FDC) on high spectral characteristics of pear leaves, (2) analyze the relationship between reflectances and FDC, and (3) establish high spectral remote sensing quantitative inversion model of FDC. The results showed that FDC increased reflectances of visible band (400~700 nrn) with maximum band of 666 nm. Absolute and relative rates of change were -10. 50% and -62. 89%, respectively. The FDC decreased reflectances of near infrared band (701 ~ 1 050 nm) with maximum band of 758 nm. Absolute and relative rates of change were 12. 04% and 41. 75%, respectively. After dustfall was removed, reflection peak of green light and absorption valley of red and blue light became prominent, and slope of 500~750 nm wake band increased when FDC was more than 20 g . m-2. While FDC just slightly affected shape and area of reflection peak of green light when FDC was less than 20 g . m-2. FDC were positive and negative correlated with reflectances of visible band and near infrared band, respectively. Maximum correlation coefficient (0. 61) showed at 663 nm. All of 7 inversion models, the model based on the first-order differential of logarithm of the reciprocal had better stability and predictive ability. The coefficient of determination(R2), root mean square error (RMSE) and relative percent deviation (RPD) of this model were 0. 78, 3. 37 and 2. 09, respectively. The results of this study can provide a certain reference basis for hyperspectral remote sensing of FDC.
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Poeira , Folhas de Planta , Pyrus , Tecnologia de Sensoriamento Remoto , Análise Espectral , Agricultura , Luz , Modelos TeóricosRESUMO
The objective of the present article is to ascertain the mechanism of hyperspectral remote sensing monitoring for soil salinization, which is of great importance for improving the accuracy of hyperspectral remote sensing monitoring. Paddy soils in Wensu, Hetian and Baicheng counties of the southern Xinjiang were selected. Hyperspectral data of soils were obtained. Soil salt content (S(t)) an electrical conductivity of 1:5 soil-to-water extracts (EC(1:5)) were determined. Relationships between S(t) and EC(1:5) were studied. Correlations between hyperspectral indices and S(t), and EC(1:5) were analyzed. The inversion accuracy of S(t) using hyperspectral technique was compared with that of EC(1:5). Results showed that: significant (p<0.01) relationships were found between S(t) and EC(1:5) for soils in Wensu and Hetian counties, and correlation coefficients were 0.86 and 0.45, respectively; there was no significant relationship between S(t) and EC(1:5) for soils in Baicheng county. Therefore, the correlations between S(t) and EC(1:5) varied with studied sites. S(t) and EC(1:5) were significantly related with spectral reflectance, first derivative reflectance and continuum-removed reflectance, respectively; but correlation coefficients between S(t) and spectral indices were higher than those between EC(1:5) and spectral indices, which was obvious in some sensitive bands for soil salinization such as 660, 35, 1229, 1414, 1721, 1738, 1772, 2309 nm, and so on. Prediction equations of St and EC(1:5) were established using multivariate linear regression, principal component regression and partial least-squares regression methods, respectively. Coefficients of determination, determination coefficients of prediction, and relative analytical errors of these equations were analyzed. Coefficients of determination and relative analytical errors of equations between S(t) and spectral indices were higher than those of equations between EC(1:5) and spectral indices. Therefore, the responses of high spectral information to St were more sensitive than those of high spectral information to EC(1:5). Accuracy of St predicted from high spectral data was higher than that of EC(1:5) estimated from high spectral data. The results of this study can provide a theoretical basis to improve hyperspectral remote sensing monitoring accuracy of soil salinization.
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The influences of iron oxide on soil reflectance, soil line parameter, organic matter spectral characterization and the shape of soil reflectance spectra were studied in the present paper with thirteen samples in several soil types, which covered a range of iron oxide content obtained from various combination of original and iron-removing samples. The results highlight that (1) a decrease on 350-570 nm and an increase on 570-2 500 nm were showed in the reflectance spectra with increasing iron oxide content. However, there was no significant correlation between iron oxide and spectral reflectance quantitatively; (2) iron oxide content had a negative linear correlation with soil line slope and a positive linear correlation with intercept, both were significant, which illustrated the feasibility of iron oxide prediction using soil line parameter; (3) the spectral characteristics of soil organic matter could be covered by iron oxide on 622-851 nm; (4) iron oxide in soil had influence on the shape of reflectance spectra after continuum removal and calculating statistical F and spectral angle.
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OBJECTIVE: To analyze the correlation of the serum free light chain elevated (sFLC) and clinical characteristics and hematological parameters of lymphoma in Chengdu area. METHODS: 249 cases of non-Hodgkin lymphoma ï¼NHLï¼ out of 274 patients with lymphoma diagnosed in Sichuan People's Hospital from April 2019 to July 2021 were selected, the sFLC, clinical features and hematological parameters of the patients were analyzed retrospectively. The difference of clinical features between the patients with normal sFLC and elevated sFLC was examined by chi-square test. The difference of hematological parameters between patients with normal sFLC and elevated sFLC were examined by chi-square test and nonparametric Mann-Whitney U test. RESULTS: Among the 249 NHL patients, 55.42% ï¼138/249ï¼ patients had an elevated sFLC, of which 9.24% ï¼23/138ï¼ were being monoclonal and 46.18% ï¼115/138ï¼ were polyclonal. The sFLC elevation was common in NHL, but varied according to the types of sFLC secretion ï¼monoclonal or polyclonalï¼, and types of lymphoma. Furthermore, there were no significant statistical differences in clinical characteristics, including age, sex, stage disease, International Prognostic Index ï¼IPIï¼, B symptoms, and bone marrow invasion between elevated sFLC and normal sFLC of the NHL patients ï¼Pï¼0.05ï¼. However, the patients with elevated sFLC had adverse hematological parameters more frequently, including higher WBC, ANC, AMC, hsCRP, Cr, Glb, LDH, and lower Hb, Alb. CONCLUSION: Elevated sFLC is associated with inferior hematological parameters, revealing the uniqueness of the diagnostic and prognostic value of sFLC in lymphoma in chengdu area.
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OBJECTIVE: To investigate the correlation between serum free light chain (sFLC) and blood routine parameters in patients with multiple myeloma (MM). METHODS: 347 patients with multiple myeloma diagnosed in Sichuan people's Hospital from April 2019 to July 2021 were selected. sFLC, serum total light chain (sTLC), peripheral blood routine, coagulation and biochemical parameters were analyzed retrospectively. The correlation analysis between sFLC and blood routine parameters were calculated by Pearson or Spearman correlation coefficients. Multiple stepwise linear regression was used to screen the combined blood routine parameters related to sFLC. The efficacy of the selected blood routine parameters eflecting sFLC level was evaluated, the Kruskal Wallis test of independent samples was used for inter group comparison, and the receiver operating characteristic (ROC) curve was drawn at the same time. RESULTS: In MM patients, sFLC was positively related with sTLCκ, sTLCλ, sTLCκ/λ, Cr, Urea, Cr and Cys_C significantly, while negatively correlated with eGFR markedly (ï½rï½≥0.3). Multivariate stepwise linear regression showed that the influence factors of sFLCκ were Cr and sTLCκ (P=0.000, P=0.003), the influence factors of sFLCλ were eGFR and sTLCλ(P=0.000, P=0.000), the sFLCκ/λ influence factor was sTLCκ/λ (P=0.032). Kruskal Wallis test of independent samples showed that Cr and sTLCκ, eGFR and sTLCλ, TLCκ/λ were good or better parameters to reflect the level of sFLCκ, sFLCλ and sFLCκ/λ in MM patients(Pï¼0.05), respectively. ROC curve analysis shows that Cr, sTLCκ, eGFR, sTLCλ and sTLCκ/λ had the ability to judge the abnormality of sFLC in MM patients (AUC=0.684-0.875, Pï¼0.05). CONCLUSION: In MM patients, sTLCκ and sTLCλ with renal function parameters could evaluate sFLCκ or sFLCλ level respectively, while sFLC κ/λ was estimated by sTLCκ/λ.
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Mieloma Múltiplo , Testes de Coagulação Sanguínea , Humanos , Cadeias Leves de Imunoglobulina , Estudos Retrospectivos , UreiaRESUMO
Background: Osteoarthritis (OA) is imposing substantial burdens on individuals and society with the aging population. Cortex Daphnes patch is widely used for symptomatic knee OA in China with a satisfying clinical efficacy; however, there is scant clinical evidence supporting its use. To evaluate its efficacy, we conducted a multicenter, non-inferiority, randomized, parallel-group study comparing Cortex Daphnes patch with topical nonsteroidal anti-inflammatory drugs in patients with knee OA (NCT02770950). Methods: A total of 264 symptomatic knee OA patients were treated with Cortex Daphnes or indomethacin cataplasms applied to affected sites once daily for 2 weeks. The primary outcome was improvement in knee pain on walking as assessed using a visual analog scale (VAS). The non-inferiority margin based on the full analysis population was set as -5 mm on the pain VAS. The secondary outcomes were changes of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, WOMAC scores for pain, function and stiffness, the 36-item Short Form Health Survey (SF-36), and global assessment of knees by the patients. Responder rates for pain VAS, WOMAC total score, and WOMAC pain were also included in the secondary outcomes. Results: The Cortex Daphnes patch was non-inferior to indomethacin cataplasms for the primary outcome with a group difference (Cortex Daphnes patch-indomethacin cataplasm) of 2.1 mm (95% confidence interval: 2.1-6.4); similar results were found in the per-protocol population. For all other outcomes, no significant differences were found in the full analysis set or in the per-protocol analysis set, except the responder rates for WOMAC pain was higher in the Cortex Daphnes patch group than in the indomethacin cataplasm group (78.4 vs. 64.7%, p = 0.022) in the per-protocol analysis set. Overall, 28.8% patients in the Cortex Daphnes patch group and 9.8% in the indomethacin cataplasm group reported treatment-related adverse events, the vast majority of which were mild-to-moderate skin irritation, resulting in only 3.8 and 0.8% of patients dropping out, respectively. Conclusion: The Cortex Daphnes patch, which provides satisfactory analgesic efficacy and enhances the physical function of the knee, as well as improving quality of life, may be a promising alternative to knee OA.
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OBJECTIVE: To investigate the expression of immunoglobulin G (IgG) and its subclasses in patients with multiple myeloma (MM) and lymphoma (LYM) and its correlation with blood cell parameters. METHODS: 129 patients with multiple myeloma and 113 patients with lymphoma diagnosed treated in Sichuan people's Hospital from January to December 2019 were selected and the total IgG and subclass IgG1, IgG2, IgG3 and IgG4, and some parameters of peripheral blood routine in patients were retrospective analyzed. Independent sample t test or nonparametric Mann Whitney U test were used for comparison between the groups. The relationship between IgG subclass and blood cell parameters was analyzed by correlation analysis. For the bivariate normal distribution data, Pearson correlation coefficient was calculated. For bivariate non normal distribution data, the Spearman correlation coefficient was calculated. RESULTS: IgG1 and IgG2 were significantly higher in patients with multiple myeloma than in patients with lymphoma (P=0.001, 0.000, respectively), but IgG3 and IgG4 were significantly lower than in patients with lymphoma (P=0.000, 0.000, respectively), and there was no significant difference for total serum IgG between the two groups (P=0.717). The results showed that the IgG4 content of male patients with multiple myeloma and lymphoma was significantly higher than that of female patients (Z=-3.191, P=0.001); the age, M%, E% of the MM patients were significantly higher than those of the patients with lymphoma (P=0.000, 0.005, 0.019), but WBC, RBC, Hb were significantly lower than those of the patients with lymphoma (P=0.013, 0.000, respectively). The results of Spearman correlation analysis showed that RBC and Hb were decreased with the increasing of IgG and IgG1 in the MM patients(r=0.254, -0.272, -0.248 and -0.289, P=0.004, 0.002, 0.005 and 0.001). With the increasing of IgG4 in the serum of patients with lymphoma, RBC and Hb showed the trendy of decreased (r=-0.240 and, -0.251, respectively, P=0.010, 0.007). CONCLUSION: The detection of IgG subclass and the correlation between IgG subclass and blood cell parameters are great value in the diagnosis and pathogenesis of multiple myeloma and lymphoma.
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Linfoma , Mieloma Múltiplo , Células Sanguíneas , Feminino , Humanos , Imunoglobulina G , Masculino , Estudos Retrospectivos , SoroRESUMO
PURPOSE: Anlotinib, a newly developed oral small-molecule receptor tyrosine kinase inhibitor (TKI), has been shown to have encouraging activity against sarcoma. The purpose of this study was to retrospectively evaluate the safety and clinical efficacy of chemotherapy combined with anlotinib plus anlotinib maintenance in advanced/metastatic soft tissue sarcoma (STS) patients in a real-world setting in China. PATIENTS AND METHODS: We retrospectively collected the medical data of thirty-two patients with advanced/metastatic STS who received chemotherapy combined with anlotinib plus anlotinib maintenance therapy. The objective response rate (ORR) and disease control rate (DCR) were calculated according to the RECIST 1.1 criteria. The progression-free rates (PFRs) at three and six months, the progression-free survival (PFS) time, and adverse events were recorded. RESULTS: On the basis of investigator assessments, two patients (6%) achieved CR (complete response) and nine patients (28%) achieved PR (partial response), with an ORR of 34%. Eleven patients (34%) achieved SD (stable disease), and ten patients (31%) achieved PD (progression disease), with a DCR of 69%. The progression-free rates (PFRs) at three and six months were 81% and 69%, respectively. The median PFS time was 8.2 months. The hematologic and non-hematologic toxicities were manageable. The most common grade 3 and 4 adverse events were febrile neutropenia (9%), leukopenia (19%), thrombocytopenia (3%), anemia (6%), anorexia (6%), vomiting (3%), and hypertension (6%). The combination therapy was generally well tolerated. CONCLUSION: Our study suggests that chemotherapy combined with anlotinib plus anlotinib maintenance therapy had good efficacy and resulted in more favorable survival with good tolerance among patients with advanced/metastatic STS.
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In mammalian early embryos, the transition from maternal to embryonic control of gene expression requires timely degradation of a subset of maternal mRNAs (MRD). Recently, zygotic genome activation (ZGA)-dependent MRD has been characterized in mouse 2-cell embryo. However, in early embryos, the dynamics of MRD is still poorly understood, and the maternal factor-mediated MRD before and along with ZGA has not been investigated. Argonaute 2 (Ago2) is highly expressed in mouse oocyte and early embryos. In this study, we showed that Ago2-dependent degradation involving RNA interference (RNAi) and RNA activation (RNAa) pathways contributes to the decay of over half of the maternal mRNAs in mouse early embryos. We demonstrated that AGO2 guided by endogenous small interfering RNAs (endosiRNAs), generated from double-stranded RNAs (dsRNAs) formed by maternal mRNAs with their complementary long noncoding RNAs (CMR-lncRNAs), could target maternal mRNAs and cooperate with P-bodies to promote MRD. In addition, we also showed that AGO2 may interact with small activating RNAs (saRNAs) to activate Yap1 and Tead4, triggering ZGA-dependent MRD. Thus, Ago2-dependent degradation is required for timely elimination of subgroups of maternal mRNAs and facilitates the transition between developmental states.
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Successful cloning by somatic cell nuclear transfer (SCNT) requires overcoming significant epigenetic barriers. Genomic imprinting is not generally regarded as such a barrier, although H3K27me3-dependent imprinting is differentially distributed in E6.5 epiblast and extraembryonic tissues. Here we report significant enhancement of SCNT efficiency by deriving somatic donor cells carrying simultaneous monoallelic deletion of four H3K27me3-imprinted genes from haploid mouse embryonic stem cells. Quadruple monoallelic deletion of Sfmbt2, Jade1, Gab1, and Smoc1 normalized H3K27me3-imprinted expression patterns and increased fibroblast cloning efficiency to 14% compared with a 0% birth rate from wild-type fibroblasts while preventing the placental and body overgrowth defects frequently observed in cloned animals. Sfmbt2 deletion was the most effective of the four individual gene deletions in improving SCNT. These results show that lack of H3K27me3 imprinting in somatic cells is an epigenetic barrier that impedes post-implantation development of SCNT embryos and can be overcome by monoallelic imprinting gene deletions in donor cells.
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Histonas , Técnicas de Transferência Nuclear , Animais , Clonagem de Organismos , Desenvolvimento Embrionário/genética , Feminino , Impressão Genômica , Histonas/metabolismo , Camundongos , Gravidez , Proteínas RepressorasRESUMO
In this work, we propose a combinative strategy based on regression and clustering for solving point set matching problems under a Bayesian framework, in which the regression estimates the transformation from the model to the sceneand the clustering establishes the correspondence between two point sets. The point set matching model is illustrated by a hierarchical directed graph, and the matching uncertainties are approximated by a coarse-to-fine variational inference algorithm. Furthermore, two Gaussian mixtures are proposed for the estimation of heteroscedastic noise and spurious outliers, and an isotropic or anisotropic covariance can be imposed on each mixture in terms of the transformed model points. The experimental results show that the proposed approach achieves comparable performance to state-of-the-art matching or registration algorithms in terms of both robustness and accuracy.
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Accurate prediction of soil organic carbon (SOC) distribution is crucial for soil resources utilization and conservation, climate change adaptation, and ecosystem health. In this study, we selected a 1300 m×1700 m solonchak sampling area in northern Tarim Basin, Xinjiang, China, and collected a total of 144 soil samples (5-10 cm). The objectives of this study were to build a Baye-sian geostatistical model to predict SOC content, and to assess the performance of the Bayesian model for the prediction of SOC content by comparing with other three geostatistical approaches [ordinary kriging (OK), sequential Gaussian simulation (SGS), and inverse distance weighting (IDW)]. In the study area, soil organic carbon contents ranged from 1.59 to 9.30 g·kg-1 with a mean of 4.36 g·kg-1 and a standard deviation of 1.62 g·kg-1. Sample semivariogram was best fitted by an exponential model with the ratio of nugget to sill being 0.57. By using the Bayesian geostatistical approach, we generated the SOC content map, and obtained the prediction variance, upper 95% and lower 95% of SOC contents, which were then used to evaluate the prediction uncertainty. Bayesian geostatistical approach performed better than that of the OK, SGS and IDW, demonstrating the advantages of Bayesian approach in SOC prediction.
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Carbono , Solo , Teorema de Bayes , China , Análise EspacialRESUMO
Increasing studies have demonstrated that altered expression of histone deacetylases (HDACs) plays a critical role in the tumorigenesis through up-regulation or down-regulation of key genes involved in cell proliferation, cell-cycle regulation and apoptosis. In the present study, the expression and function of HDAC9 were investigated in osteosarcoma. Quantitative real-time PCR and Western blot analysis found that HDAC9 was up-regulated in osteosarcoma tissues, when compared with that in adjacent normal tissues. In vitro studies further demonstrated that overexpression of HDAC9 in U2OS and MG63 cells promoted cell proliferation and invasion. Using chromatin immunoprecipitation (ChIP) assay, we found that HDAC9 epigenetically repressed p53 transcription through binding to its proximal promoter region. Therefore, our data suggest an important role for HDAC9/p53 regulatory pathway in the osteosarcoma progression.