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BACKGROUND: The mechanism of body growth in mammals is poorly understood. Here, we investigated the regulatory networks involved in body growth through transcriptomic analysis of pituitary and epiphyseal tissues of smaller sized Debao ponies and Mongolian horses at the juvenile and adult stages. RESULTS: We found that growth hormone receptor (GHR) was expressed at low levels in long bones, although growth hormone (GH) was highly expressed in Debao ponies compared with Mongolian horses. Moreover, significant downregulated of the GHR pathway components m-RAS and ATF3 was found in juvenile ponies, which slowed the proliferation of bone osteocytes. However, WNT2 and PLCß2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of the bone extracellular matrix. Furthermore, we found that the WNT/Ca2+ pathway may be responsible for regulating body growth. GHR was demonstrated by q-PCR and Western blot analyses to be expressed at low levels in long bones of Debao ponies. Treatment with WNT antagonistI decreased the expression of WNT pathway components (P < 0.05) in vitro. Transduction of ATDC5 cells with a GHR-RNAi lentiviral vector decreased the expression of the GHR pathway components (P < 0.05). Additionally, the expression of the IGF-1 gene in the liver was lower in Debao ponies than in Mongolian horses at the juvenile and adult stages. Detection of plasma hormone concentrations showed that Debao ponies expressed higher levels of IGF-1 as juveniles and higher levels of GH as adults than Mongolian horses, indicating that the hormone regulation in Debao ponies differs from that in Mongolian horses. CONCLUSION: Our work provides insights into the genetic regulation of short stature growth in mammals and can provide useful information for the development of therapeutic strategies for small size.
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Nanismo , Hormônio do Crescimento Humano , Animais , Tamanho Corporal , Hormônio do Crescimento/genética , Cavalos , Fator de Crescimento Insulin-Like IRESUMO
A concise copper catalysis strategy for the addition-cyclization of cyclic oxime esters across 1,6-enynes with high stereoselectivity to generate 1-indanones bearing an all-carbon quaternary center is reported. In this process, single-electron reduction of cyclic oxime esters enables deconstructive carbon-carbon cleavage to provide a key cyanopropyl radical poised for the addition-cyclization. This reaction is redox-neutral, exhibits good functional group compatibility, and features 100% atomic utilization. This process driven by copper catalyst makes readily available cyclic oxime esters as bifunctional reagents to demonstrate convergent synthesis.
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Plant roots rely on inorganic orthophosphate (Pi) transporters to acquire soluble Pi from soil solutions that exists at micromolar levels in natural ecosystems. Here, we functionally characterized a rice (Oryza sativa) Pi transporter, Os Phosphate Transporter-1;3 (OsPHT1;3), that mediates Pi uptake, translocation, and remobilization. OsPHT1;3 was directly regulated by Os Phosphate Starvation Response-2 and, in response to Pi starvation, showed enhanced expression in young leaf blades and shoot basal regions and even more so in roots and old leaf blades. OsPHT1;3 was able to complement a yeast mutant strain defective in five Pi transporters and mediate Pi influx in Xenopus laevis oocytes. Overexpression of OsPHT1;3 led to increased Pi concentration both in roots and shoots. However, unlike that reported for other known OsPHT1 members that facilitate Pi uptake at relatively higher Pi levels, mutation of OsPHT1;3 impaired Pi uptake and root-to-shoot Pi translocation only when external Pi concentration was below 5 µm Moreover, in basal nodes, the expression of OsPHT1;3 was restricted to the phloem of regular vascular bundles and enlarged vascular bundles. An isotope labeling experiment with 32P showed that ospht1;3 mutant lines were impaired in remobilization of Pi from source to sink leaves. Furthermore, overexpression and mutation of OsPHT1;3 led to reciprocal alteration in the expression of OsPHT1;2 and several other OsPHT1 genes. Yeast-two-hybrid, bimolecular fluorescence complementation, and coimmunoprecipitation assays all demonstrated a physical interaction between OsPHT1;3 and OsPHT1;2. Taken together, our results indicate that OsPHT1;3 acts as a crucial factor for Pi acquisition, root-to-shoot Pi translocation, and redistribution of phosphorus in plants growing in environments with extremely low Pi levels.
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Oryza/metabolismo , Proteínas de Transporte de Fosfato/metabolismo , Fosfatos/metabolismo , Proteínas de Plantas/metabolismo , Animais , Transporte Biológico , Feminino , Regulação da Expressão Gênica de Plantas , Mutação , Oócitos/metabolismo , Oryza/genética , Floema/genética , Floema/metabolismo , Proteínas de Transporte de Fosfato/genética , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Plantas Geneticamente Modificadas , Mapas de Interação de Proteínas , Técnicas do Sistema de Duplo-Híbrido , Xenopus laevisRESUMO
OBJECTIVE: To explore the effect of IL-8 on the epithelial-to-mesenchymal transition (EMT) in ovarian cancer,which will provide experimental basis for revealing related molecular mechanism in malignant metastasis of ovarian cancer. METHODS: The migration of ovarian cancer cell line SKOV3 cells was explored with Real time label free cell analysis (RTCA) after treatment with recombinant human IL-8.SKOV3 cells were co-cultured with IL-8 for 48 h,proteins involved in EMT were investigated via Western blot to explore the effect of IL-8 on the activation of the EMT. Invasion of SKOV3 cells after treatment with IL-8 were evaluated by transwell assay. RESULTS: According to the results of RTCA,after treatment with IL-8 for 48 h,the migration of SKOV3 cells was in platform phase. The treatment of IL-8 unregulated vimentin and snail and downregulated E-cadherin,which suggested that IL-8 induced EMT in ovarian cancer. The results of transwell test showed that invasive ability of IL-8 pretreated SKOV3 cells was enhanced (P<0.05). CONCLUSION: IL-8 can induce the EMT of ovarian cancer and enhance the invasion and migration of ovarian cancer.
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Transição Epitelial-Mesenquimal , Interleucina-8/farmacologia , Neoplasias Ovarianas/patologia , Vimentina/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Invasividade Neoplásica , Fatores de Transcrição da Família Snail/metabolismoRESUMO
In the title compound, [Zn(NCS)2(C24H22N4O)]·C3H7NO, the Zn(II) cation is N,N',N''-chelated by one 2-({4-[2,6-bis-(pyridin-2-yl)pyridin-4-yl]phen-yl}(meth-yl)amino)-ethanol ligand and coordinated by two thio-cyanate anions in a distorted N5 trigonal-bipyramidal geometry. In the mol-ecule, the three pyridine rings are approximately coplanar [maximum deviation = 0.026â (5)â Å], and the mean plane of the three pyridine rings is twisted to the benzene ring with a small dihedral angle of 5.9â (2)°. In the crystal, complex mol-ecules are linked by weak C-Hâ¯O hydrogen bonds into supra-molecular chains propagated along [110]; π-π stacking is observed between adjacent chains [centroid-centroid distance = 3.678â (4)â Å]. The di-methyl-formamide solvent mol-ecules are linked with the complex chains via weak C-Hâ¯O hydrogen bonds.
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There are two independent mol-ecules in the asymmetric unit of the title mol-ecule, C8H9N3S2, both of which exhibit an E conformation with the pyridine ring and di-thio-carbazate fragment located on opposite sides of the C=N bond. The pyridine ring and di-thio-carbazate group are approximately coplanar, with dihedral angles of 4.74â (1) and 8.77â (1)° between their planes in the two mol-ecules. In the crystal, mol-ecules are linked to each other via N-Hâ¯N hydrogen bonds, forming zigzag chains parallel to [10-1].
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OBJECTIVE: This study aimed to investigate the effect of preoperative current smoking on chronic postsurgical pain in patients who underwent thoracic surgery. METHODS: A total of 5,395 patients aged over 18 years old who underwent thoracic surgery from January 2016 to March 2020 in Henan Provincial People's Hospital were enrolled. Patients were divided into two groups: the smoking group (SG group) and the nonsmoking group (NSG group). Propensity score matching was utilized to eliminate the influence of confounding factors, and a multivariable logistic regression model was established to determine the effect of preoperative current smoking on chronic postsurgical pain. The dose-response relationship between the smoking index (SI) and chronic postsurgical pain at rest was analyzed using a restricted cubic spline curve. RESULTS: In a matched cohort of 1028 patients, the incidence of chronic pain at rest was 13.2% in the smoking group and 19.0% in the nonsmoking group (P = 0.011). Three different models were used to verify the stability of the model between preoperative current smoking and chronic postsurgical pain. A regression model was established to determine the influence of different smoking indexes (SIs) on chronic postsurgical pain. The incidence of chronic pain at rest was lower in patients with SI ≥400 before thoracic surgery than in patients whose SI was less than 400. CONCLUSIONS: A relationship between the preoperative current smoking index and chronic postsurgical pain at rest was observed. The incidence of chronic postsurgical pain at rest was lower in patients whose SI was greater than 400.
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Background: The effect of sex and age on chronic post-thoracic surgical pain (CPTP) at rest and with activity remains unclear. The main purpose of this study was to investigate the relationship between the incidence of chronic postoperative pain (at rest and with activity) and sex/age differences. Methods: This was a single-center retrospective study that included adult patients who had undergone elective thoracic surgery. Patients were divided into two groups based on sex. Demographic and perioperative data were collected, including age, sex, education level, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) physical status, and medical history (hypertension, diabetes mellitus). Chronic postoperative pain data were collected by telephone follow-up. Results: Among the 3,159 patients enrolled, 1,762 were male, and 1,397 were female. After creating a matched-pairs cohort, 1,856 patients were analyzed. The incidence of CPTP at rest was 14.9% among males and 17.8% among females (p = 0.090). The incidence of CPTP with activity was 28.4% among males and 35.0% among females (p = 0.002). We analyzed three different models after propensity matching to validate the stability of the prediction model between sex and CPTP, and female sex was a significant predictor of CPTP with activity 3 months after surgery. Further analysis showed that females in the 45-55-year-old age group were more prone to develop CPTP. Conclusion: Females have a higher incidence of chronic postoperative pain with activity after thoracic surgery. Females in the 45-55-year-old age group are more prone to develop CPTP than females in other age groups.
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A new copper/silver-co-mediated three-component bicyclization of benzene-linked 1,6-enynes with ICF2CO2Et with TMSN3 was reported, and used to produce a wide range of hitherto unreported difluorinated tetrahydroindeno[1,2-c]azepine-3,6-diones with moderate to good yields. The mechanistic pathway consists of radical-induced 1,6-addition-cyclization, oxidative addition, reductive elimination, nitrene insertion and N-O cleavage, resulting in continuous multiple bond-forming events including C-C and C-N bonds to build up a 6/5/7 tricyclic framework.
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In the title compound, C(20)H(18)N(4)·CH(3)COOH, the benzene ring forms dihedral angles of 81.34â (11) and 54.32â (11)° with the two pyridine rings. In the crystal, inter-molecular O-Hâ¯N hydrogen bonding links one 1,5-benzodiazepine mol-ecule and one acetic acid solvent mol-ecule into a dimer. These dimers, related by translation along the b axis, are further linked into chains via weak inter-molecular N-Hâ¯N hydrogen bonds.
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OBJECTIVE: To investigate the effect of irradiation on matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF) and microvessel density (MVD), which influence on tumor growth and metastases of mice bearing Lewis lung cancer (LLC). METHODS: C57BL/6 mice bearing LLC were randomized into two groups to receive radiation and no-radiation, respectively. When tumor reached about 190 mm3 in volume on the fourteenth day after inoculation, the radiation group was irradiated to the primary tumor (6MV-X, 5 Gy/day, d14, 16, 18, 20). On the eighth day after irradiation, animals were killed to examine primary tumors, normal tissue near tumors. MMP-2, MMP-9, VEGF and MVD were checked by immunohistochemical means. RESULTS: Immunohistochemical examination demonstrated an increased expression of MMP2, MMP9, VEGF and MVD in the tumor tissue of the radiation group (P<0.05). Additionally, the expression levels of MMP2 and MMP9 in the tumor tissue were higher than those in the normal tissue near tumor (P<0.05). CONCLUSION: This study showed that irradiation might increased MMP2, MMP9, VEGF and MVD expression in the tumor tissue of mice bearing Lewis lung cancer. Our finding supports a potential way to overcome tumor metastasis induced by radiation if MMP inhibitor and anti-vascularization are combined to irradiation clinically.
Assuntos
Carcinoma Pulmonar de Lewis/radioterapia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Patológica/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/efeitos da radiação , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neovascularização Patológica/radioterapia , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/efeitos da radiaçãoRESUMO
BACKGROUND & OBJECTIVE: Intensity-modulated radiation therapy (IMRT) can improve the dose distribution in the breast irradiation for early stage breast cancer, but the definition and delineation for clinical target volume (CTV) are uncertain. This study was to investigate the impact of skin build-up region on evaluation of IMRT plan for early stage breast cancer by analyzing dose-volume histograms (DVHs). METHODS: CTVs for 22 patients with early stage breast cancer were delineated on transversal CT images, which included the skin build-up region. The CTVs were contracted and modified to exclude 0.5 cm outer skin surface to form new target volumes (CTV1s). All plans were tailored by using step-and-shoot IMRT techniques. DVHs and dose distributions of these plans were evaluated. RESULTS: The percentage volume receiving more than 95% of the prescription dose (V95) for CTV was significantly lower than that for CTV1 [(89.6+/-3.2)% vs. (96.5+/-2.0)%, P<0.001]. The homogeneity index of the dose distribution within targets (D99-01) for CTV was significantly higher than that for CTV1 [(14.0+/-2.4) Gy vs. (7.3+/-1.6) Gy, P<0.001]. CONCLUSIONS: The surface effect of skin build-up region is important and must be considered in IMRT for breast cancer. It is better to use the CTV excluding surface and build-up region to evaluate such plans.