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Proliferating mammalian cells use glutamine as a source of nitrogen and as a key anaplerotic source to provide metabolites to the tricarboxylic acid cycle (TCA) for biosynthesis. Recently, mammalian target of rapamycin complex 1 (mTORC1) activation has been correlated with increased nutrient uptake and metabolism, but no molecular connection to glutaminolysis has been reported. Here, we show that mTORC1 promotes glutamine anaplerosis by activating glutamate dehydrogenase (GDH). This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH. Mechanistically, mTORC1 represses SIRT4 by promoting the proteasome-mediated destabilization of cAMP-responsive element binding 2 (CREB2). Thus, a relationship between mTORC1, SIRT4, and cancer is suggested by our findings. Indeed, SIRT4 expression is reduced in human cancer, and its overexpression reduces cell proliferation, transformation, and tumor development. Finally, our data indicate that targeting nutrient metabolism in energy-addicted cancers with high mTORC1 signaling may be an effective therapeutic approach.
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Glutamina/metabolismo , Proteínas Mitocondriales/metabolismo , Neoplasias/metabolismo , Sirtuinas/metabolismo , Factores de Transcripción Activadores/metabolismo , Animales , Proliferación Celular , Embrión de Mamíferos/citología , Metabolismo Energético , Glutamato Deshidrogenasa/metabolismo , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones , Complejos Multiproteicos , Trasplante de Neoplasias , Neoplasias/patología , Serina-Treonina Quinasas TOR/metabolismo , Transcripción Genética , Trasplante Heterólogo , Proteína 2 del Complejo de la Esclerosis Tuberosa , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , UbiquitinaciónRESUMEN
Rice blast is one of the most hazardous diseases affecting rice production. Previously, we discovered that the Atp2 protein of Rhodopseudomonas palustris could significantly inhibit the appressorium formation and pathogenicity of Magnaporthe oryzae. However, the molecular mechanism of this fungus has remained unknown. This study revealed that Atp2 can enter the cell and interact with the ribosomal protein MoRpl12 of M. oryzae, directly affecting the expression of the MoRpl12 protein. Silencing the MoRPL12 gene can affect cell wall integrity, growth, conidiogenesis, and fungal pathogenicity. The quantitative reverse transcription PCR results showed significant changes in the expression of conidiation-related genes in the MoRPL12 gene-silenced mutants or in the Atp2 protein-treated plants. We further found that Atp2 treatment can influence the expression of ribosomal-related genes, such as RPL, in M. oryzae. Our study revealed a novel antifungal mechanism by which the Atp2 protein binds to the ribosomal protein MoRpl12 and inhibits the pathogenicity of rice blast fungus, providing a new potential target for rice blast prevention and control.
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Proteínas Bacterianas , Proteínas Fúngicas , Oryza , Enfermedades de las Plantas , Rhodopseudomonas , Proteínas Ribosómicas , Oryza/microbiología , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Enfermedades de las Plantas/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Rhodopseudomonas/genética , Rhodopseudomonas/metabolismo , Ascomicetos/efectos de los fármacos , Ascomicetos/genética , Ascomicetos/patogenicidad , Regulación Fúngica de la Expresión Génica , Antifúngicos/farmacología , Esporas FúngicasRESUMEN
Glucose-6-phosphate dehydrogenase (G6PD) is involved in triple-negative breast cancer (TNBC) progression. Metabolic crosstalk between cancer cells and tumor-associated macrophages mediates tumor progression in TNBC. Molecular biological methods were applied to clarify the mechanism of the crosstalk between TNBC cells and M2 macrophages. In the present study, we verified that G6PD overexpression drives M2 macrophage polarization by directly combining with phospho-STAT1 and upregulating CCL2 and TGF-ß1 secretion in TNBC cells. In turn, M2-like TAMs activated TNBC cells through IL-10 secretion, providing feedback to upregulate G6PD and promote TNBC cell migration and proliferation in vitro. Furthermore, we found that 6-AN (a specific inhibitor of G6PD) not only suppressed the cancer-driven polarization of macrophages toward the M2 phenotype but also inhibited the inherent M2 polarization of macrophages. Targeting the G6PD-regulated pentose phosphate pathway restrained TNBC progression and M2-type polarization of macrophages in vitro and in vivo.
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Glucosafosfato Deshidrogenasa , Neoplasias de la Mama Triple Negativas , Humanos , Línea Celular Tumoral , Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/metabolismo , Macrófagos/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Microambiente TumoralRESUMEN
OBJECTIVE: To investigate the independent effects of irisin on insulin resistance (IR) in ovary of polycystic ovary syndrome (PCOS) and explore possible pathways. METHODS: We established PCOS medel using Poretsky L's method, then PCOS rats were randomly divided into model group (M) and irisin group (I), and normal rats (N) were used as the control. Then rats in the group I were injected with recombinant irisin. Then the levels of circulating fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of IR (HOMA-IR) and PI3K/AKT and MAPK/ERK pathways in each group were observed, as well as the effects of irisin on the levels of circulating HOMA-IR and PI3K/AKT and MAPK/ERK pathways in ovary of PCOS rats were evaluated. RESULTS: Compared with normal group, levels of FBG, FINS, and HOMA-IR of model group were significantly increased (p < 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p-PI3K, PI3K, p-AKT, and AKT (p = 0.015, p = 0.010, p = 0.005, and p = 0.009, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.001, and p = 0.005, respectively) were decreased, while the levels of average optical density of p-ERK, ERK (p = 0.011, and p = 0.013, respectively) and level of mRNA concentration of ERK (p < 0.001) were increased in ovary. After irisin intervention, compared with model group, levels of FBG, FINS, and HOMA-IR of rats in irisin group were significantly decreased (p = 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p-PI3K, PI3K, p-AKT, and AKT (p = 0.030, p = 0.024, p = 0.012, and p = 0.025, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.002, and p = 0.003, respectively) were significantly increased, while the levels of average optical density of p-ERK, ERK (p = 0.004, and p = 0.026, respectively) and level of mRNA concentration of ERK (p = 0.001) were significantly decreased. CONCLUSION: Our study demonstrated that irisin could not only improve circulating insulin resistance, but may also improve ovarian IR through an increase in the activity of PI3K/AKT signaling and a decrease of MAPK/ERK signaling.
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Fibronectinas , Resistencia a la Insulina , Sistema de Señalización de MAP Quinasas , Ovario , Síndrome del Ovario Poliquístico , Proteínas Proto-Oncogénicas c-akt , Animales , Femenino , Síndrome del Ovario Poliquístico/metabolismo , Fibronectinas/metabolismo , Ratas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ovario/metabolismo , Ovario/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ratas Sprague-Dawley , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismoRESUMEN
Pepper anthracnose caused by Colletotrichum gloeosporioides infection is an important fungal disease and represents a serious threat to pepper yield and quality. At present, the pathogenic molecular mechanism of C. gloeosporioides is not very clear. In our study, we characterized the function of C. gloeosporioides CgNis1, a homolog of Magnaporthe oryzae MoNis1. We found that the ∆Cgnis1 mutant reduced the growth rate and was defective in conidiation. Although the rate of appressorium formation was unaffected, the germ tube was found to be abnormal. CgNis1 was shown to be involved in the H2O2 stress response and maintaining cell membrane permeability. The pathogenicity assays performed in this study indicated that the deletion of CgNIS1 is associated with virulence. Our results indicate that CgNis1 is necessary for the growth, development, and pathogenicity of the fungus. This work provides an in-depth analysis of the Nis1 protein, helps to enhance studies on pathogen-related molecular mechanisms, and provides a theoretical basis for the prevention and control of C. gloeosporioides in peppers.
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Colletotrichum , Peróxido de Hidrógeno , Virulencia/genética , Peróxido de Hidrógeno/metabolismo , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMEN
BACKGROUND: Robotic hepatectomy (RH) has gradually been accepted as it has overcome some of the limitations of open hepatectomy (OH). This study was to compare short-term outcomes in RH and OH for overweight (preoperative body mass index ≥ 25 kg/m²) patients with hepatocellular carcinoma (HCC). METHODS: Perioperative and postoperative data from these patients who underwent RH or OH between January 2010 and December 2020 were retrospectively analyzed. Propensity score matching (PSM) analysis was performed to determine the impact of RH versus OH on the prognosis of overweight HCC patients. RESULTS: All 304 overweight HCC patients were included, 172 who were underwent RH, and 132 who were underwent OH. After the 1:1 PSM, there were 104 patients in both RH and OH groups. After PSM, the RH group of patients had a shorter operative time, less estimated blood loss (EBL), a longer total clamping time, a shorter postoperative length of stay (LOS), less chance of surgical site infection and less rates of blood transfusion (all P < 0.05) compared to the OH patients. The differences between operative time, EBL and LOS were more significant in obese patients. RH was found to be an independent protective factor of EBL ≥ 400ml relative to OH in overweight patients for the first time. CONCLUSIONS: RH was safe and feasible in overweight HCC patients. Compared with OH, RH has advantages in terms of operative time, EBL, postoperative LOS, and surgical site infection. Carefully selected overweight patients should be considered for RH.
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Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Resultado del Tratamiento , Estudios Retrospectivos , Puntaje de Propensión , Infección de la Herida Quirúrgica/cirugía , Hepatectomía , Sobrepeso/complicaciones , Tiempo de InternaciónRESUMEN
This paper proposes an adaptive threshold segmentation algorithm for the magnesium ingot stack based on image overexposure area correction (ATSIOAC), which solves the problem of mirror reflection on the surface of magnesium alloy ingots caused by external ambient light and auxiliary light sources. Firstly, considering the brightness and chromaticity information of the mapped image, we divide the exposure probability threshold into weak exposure and strong exposure regions. Secondly, the saturation difference between the magnesium ingot region and the background region is used to obtain a mask for the magnesium ingot region to eliminate interference from the image background. Then, the RGB average of adjacent pixels in the overexposed area is used as a reference to correct the colors of the strongly exposed and weakly exposed areas, respectively. Furthermore, in order to smoothly fuse the two corrected images, pixel weighted average (WA) is applied. Finally, the magnesium ingot sorting experimental device was constructed and the corrected top surface image of the ingot pile was segmented through ATSIOAC. The experimental results show that the overexposed area detection and correction algorithm proposed in this paper can effectively correct the color information in the overexposed area, and when segmenting ingot images, complete segmentation results of the top surface of the ingot pile can be obtained, effectively improving the accuracy of magnesium alloy ingot segmentation. The segmentation algorithm achieves a segmentation accuracy of 94.38%.
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BACKGROUND: Salvage surgery after conversion therapy with a combination of tyrosine kinase inhibitor and anti-programmed death-1 antibody has shown improved survival benefits in patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). We aimed to compare the survival benefits in a retrospective cohort of patients with HCC with PVTT who underwent salvage surgery after conversion therapy and surgery alone. METHODS: From January 2015 to October 2021, we selected patients diagnosed with HCC with PVTT who underwent liver resection at Chinese PLA General Hospital. The primary endpoint in the comparison of survival benefits between conversion therapy and surgery-alone groups was recurrence-free survival. Propensity score matching was applied to reduce any potential bias in the study. RESULTS: The 6-, 12-, and 24-month recurrence-free survival rates in the conversion and surgery alone groups were 80.3% vs 36.5%, 65.4% vs 29.4%, and 56% vs 21%, respectively. On multivariable Cox regression analyses, conversion therapy significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone. CONCLUSIONS: For patients with HCC with PVTT, surgery after conversion therapy is in relationship with increased survival in comparison with surgery alone.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombosis de la Vena , Humanos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/cirugía , Puntaje de Propensión , Estudios Retrospectivos , Vena Porta/cirugía , Vena Porta/patología , Trombosis de la Vena/etiología , Trombosis de la Vena/cirugía , Trombosis de la Vena/patologíaRESUMEN
BACKGROUND: Laparoscopy was considered the standard method of left lateral sectionectomy. The robotic approach showed advantages in complex cases of left lateral sectionectomy. However, the impact of the robotic system on ordinary cases is still unknown. METHODS: Retrospective review of consecutive robotic left lateral sectionectomy (R-LLS) and laparoscopic left lateral sectionectomy (L-LLS) from January 2015 to December 2019. Univariate and multivariate logistic regression was used to determine the effects of surgical method and surgical complexity on postoperative length of stay, surgical and overall cost. RESULTS: 258 consecutive patients who underwent minimally invasive left lateral sectionectomy were analyzed. L-LLS had comparable outcomes and decreased surgery (USD 2416.3 vs 4624.5; p < 0.001) and overall costs (USD 8004.5 vs 11897.1; p < 0.001) compared with R-LLS in the ordinary-case group, whereas R-LLS was associated with shorter postoperative LOS (5.0 vs 3.5 days; p = 0.004) in the complex-case group. On multivariable analysis, R-LLS was predictive of shorter postoperative LOS [odds ratio (OR) 0.388, 95% confidence interval (CI) 0.198-0.760, p = 0.006], whereas R-LLS was predictive of higher surgery (OR 65.640, 95% CI 17.406-247.535, p < 0.001) and overall costs (OR 102.233, 95% CI 22.241-469.931, p < 0.001). CONCLUSION: Results of this study showed no clinical benefit to the R-LLS compared with L-LLS in ordinary cases. R-LLS had potential advantages in selected complex cases.
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Laparoscopía , Neoplasias Hepáticas , Procedimientos Quirúrgicos Robotizados , Hepatectomía/métodos , Humanos , Laparoscopía/métodos , Tiempo de Internación , Hígado , Neoplasias Hepáticas/cirugía , Tempo Operativo , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Robotic liver resection (RLR) has increasingly been accepted as it has overcome some of the limitations of open liver resection (OLR), while the outcomes following RLR in elderly patients with hepatocellular carcinoma (HCC) are still uncertain. This study aimed to evaluate the short and long-term outcomes of RLR vs. OLR in elderly HCC patients. METHODS: Perioperative data of elderly patients (≥ 65 years) with HCC who underwent RLR or OLR between January 2010 and December 2020 were retrospectively analyzed. A 1:2 propensity score-matched (PSM) analysis was performed to minimize the differences between RLR and OLR groups. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients. RESULTS: Of the 427 elderly HCC patients included in this study, 113 underwent RLR and 314 underwent OLR. After the 1:2 PSM, there were 100 and 178 patients in the RLR and the OLR groups, respectively. The RLR group had a less estimated blood loss (EBL), a shorter postoperative length of stay (LOS), and a lower complications rate (all P < 0.05), compared with the OLR group before and after PSM. Univariable and multivariable analyses showed that advanced age and surgical approaches were not independent risk factors for long-term prognosis. The two groups of elderly patients who were performed RLR or OLR had similar OS (median OS 52.8 vs. 57.6 months) and RFS (median RFS 20.4 vs. 24.6 months) rates after PSM. CONCLUSIONS: RLR was comparable to OLR in feasibility and safety. For elderly patients with HCC, RLR resulted in similar oncologic and survival outcomes as OLR.
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Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Anciano , Puntaje de Propensión , Estudios Retrospectivos , Laparoscopía/métodos , Hepatectomía/métodos , Tiempo de InternaciónRESUMEN
Non-small cell lung cancer (NSCLC) accounts for 85~90% of lung cancer cases, with a poor prognosis and a low 5-year survival rate. Sphingosine kinase-1 (SPHK1), a key enzyme in regulating sphingolipid metabolism, has been reported to be involved in the development of NSCLC, although the underlying mechanism remains unclear. In the present study, we demonstrated the abnormal signature of SPHK1 in NSCLC lesions and cell lines of lung cancers with a potential tumorigenic role in cell cycle regulation. Functionally, ectopic Pre-B cell leukemia homeobox-1 (PBX1) was capable of restoring the arrested G1 phase induced by SPHK1 knockdown. However, exogenous sphingosine-1-phosphate (S1P) supply had little impact on the cell cycle arrest by PBX1 silence. Furthermore, S1P receptor S1PR3 was revealed as a specific switch to transport the extracellular S1P signal into cells, and subsequently activated PBX1 to regulate cell cycle progression. In addition, Akt signaling partially participated in the SPHK1/S1PR3/PBX1 axis to regulate the cell cycle, and the Akt inhibitor significantly decreased PBX1 expression and induced G1 arrest. Targeting SPHK1 with PF-543 significantly inhibited the cell cycle and tumor growth in preclinical xenograft tumor models of NSCLC. Taken together, our findings exhibit the vital role of the SPHK1/S1PR3/PBX1 axis in regulating the cell cycle of NSCLC, and targeting SPHK1 may develop a therapeutic effect in tumor treatment.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Puntos de Control del Ciclo Celular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Lisofosfolípidos/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol) , Factor de Transcripción 1 de la Leucemia de Células Pre-B , Proteínas Proto-Oncogénicas c-akt/metabolismo , Esfingosina/metabolismo , AnimalesRESUMEN
BACKGROUND: Alpha-lipoic acid (ALA) is a natural compound, one of the natural antioxidants with high activity. In the NADPH oxidase family, NADPH oxidase 4 (NOX4) is an important subunit participating in the production of ROS. NADPH oxidase 2 (NOX2) can form active NADPH oxidase complexes when binding to several other subunits in the cytoplasm, and NOX2 is its major functional subunit. Rapid atrial pacing (RAP) model was constructed to study the effects of ALA on electrical and structural remodeling in rabbits. METHODS: Thirty rabbits were divided into SHAM group, RAP group and ALA+RAP group. Their right atriums were paced at a speed of 600 beats/min for 12 h in the RAP and ALA+RAP groups, and the atrial effective refractory period (AERP) and AERP frequency adaptability were determined during the pace. In ALA+RAP group, ALA (30 mg/kg) was administered intraperitoneally daily to the rabbits for 3 days before RAP. Atrial tissue was collected from each group to detect malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) to observe the effect of oxidative stress. The pathological structure of the atrial tissue was observed through hematoxylin-eosin (HE) staining. Ultrastructural changes in the atrial myocytes were observed by transmission electron microscopy (TEM), and the expression levels of Nox2 and Nox4 were detected by immunohistochemistry, western blot and ELISA. RESULTS: AERP gradually shortened, while ALA injection could remarkably delay this process. HE staining showed that the most of the nuclei appeared normal, the myocardial fibers did not show ruptures, and their arrangement was slightly ordered, and myofilament dissolution and mitochondrial swelling and deformation were rarely observed by TEM in the ALA+RAP group. Compared with the RAP group, the contents of MDA and ROS were reduced, SOD activity was enhanced, and the expression of NOX2 and NOX4 was decreased in the ALA+RAP group. DISCUSSION: ALA can inhibit atrial electrical remodeling and structural remodeling, and its mechanism may be related to inhibiting the activity of NADPH oxidase.
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Fibrilación Atrial , Remodelación Atrial , Ácido Tióctico , Animales , Conejos , Ácido Tióctico/farmacología , NADPH Oxidasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Remodelación Atrial/fisiología , Superóxido DismutasaRESUMEN
OBJECTIVE: The aim of this study is to investigate the effect of irisin on leukemia inhibitory factor (LIF) and integrin αvß3 in implantation failure uterus. METHODS: Early pregnant rats were randomly divided into normal group (N), mifepristone treated group (M), irisin group (I) and progestin group (P). The implantation failure model was established using mifepristone. Second, we evaluated the average number of embryos and detected the expression of LIF and integrin αvß3 protein and mRNA in endometrium. RESULTS: Compared with group M, the average number of embryos was significantly higher in group N, P and I, the expression of LIF and integrin αvß3 in endometrium was significantly higher in group N, P and I. CONCLUSION: Irisin could improve the poor receptive state of endometrium by promoting LIF and integrin αvß3 secretion to improve blastocyst implantation in rats of implantation failure.
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Implantación del Embrión/efectos de los fármacos , Fibronectinas/farmacología , Integrina alfaVbeta3/genética , Factor Inhibidor de Leucemia/genética , Animales , Implantación del Embrión/genética , Pérdida del Embrión/inducido químicamente , Pérdida del Embrión/genética , Pérdida del Embrión/metabolismo , Pérdida del Embrión/patología , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Femenino , Fibronectinas/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Inyecciones Intramusculares , Integrina alfaVbeta3/metabolismo , Factor Inhibidor de Leucemia/metabolismo , Mifepristona/farmacología , Embarazo , Progestinas/administración & dosificación , Progestinas/farmacología , Ratas , Ratas WistarRESUMEN
In general, hydrostatic pressure can suppress electrical polarization, instead of creating and/or enhancing polarization like strain engineering. Here, a combination of first-principles calculations and CALYPSO crystal structures prediction is used to point out that hydrostatic pressure applied on antiperovskite MgCNi3 can stabilize polarization with metallicity, and thus a polar metal can exist under high pressure. Strikingly, the metallic polar phase of MgCNi3 exhibits an original linear-cubic coupling between polar and nonpolar modes, resulting in an asymmetrical double-well when the polarization is switched. Moreover, another novel phase of MgCNi3 under high pressure possesses an enhanced hardness stemming from a robust s-s electrons interaction of an unexpected C-C bond, rather than typical sp3 orbital hybridization. These discoveries open new routes to design superhard materials and polar metals.
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The solution of the dynamic equations of the six-axis accelerometer is a prerequisite for sensor calibration, structural optimization, and practical application. However, the forward dynamic equations (FDEs) and inverse dynamic equations (IDEs) of this type of system have not been completely solved due to the strongly nonlinear coupling relationship between the inputs and outputs. This article presents a comprehensive study of the FDEs and IDEs of the six-axis accelerometer based on a parallel mechanism. Firstly, two sets of dynamic equations of the sensor are constructed based on the Newton-Euler method in the configuration space. Secondly, based on the analytical solution of the sensor branch chain length, the coordination equation between the output signals of the branch chain is constructed. The FDEs of the sensor are established by combining the coordination equations and two sets of dynamic equations. Furthermore, by introducing generalized momentum and Hamiltonian function and using Legendre transformation, the vibration differential equations (VDEs) of the sensor are derived. The VDEs and Newton-Euler equations constitute the IDEs of the system. Finally, the explicit recursive algorithm for solving the quaternion in the equation is given in the phase space. Then the IDEs are solved by substituting the quaternion into the dynamic equations in the configuration space. The predicted numerical results of the established FDEs and IDEs are verified by comparing with virtual and actual experimental data. The actual experiment shows that the relative errors of the FDEs and the IDEs constructed in this article are 2.21% and 7.65%, respectively. This research provides a new strategy for further improving the practicability of the six-axis accelerometer.
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MicroRNAs (miRNAs) are a class of small non-coding RNAs, which direct post-transcriptional gene silencing (PTGS) and function in a vast range of biological events including cancer development. Most miRNAs pair to the target sites through seed region near the 5' end, leading to mRNA cleavage and/or translation repression. Here, we demonstrated a miRNA-induced dual regulation of heme oxygenase-1 (HO-1) via seed region and non-seed region, consequently inhibited tumor growth of NSCLC. We identified miR-1254 as a negative regulator inhibiting HO-1 translation by directly targeting HO-1 3'UTR via its seed region, and suppressing HO-1 transcription via non-seed region-dependent inhibition of transcriptional factor AP-2 alpha (TFAP2A), a transcriptional activator of HO-1. MiR-1254 induced cell apoptosis and cell cycle arrest in human non-small cell lung carcinoma (NSCLC) cells by inhibiting the expression of HO-1, consequently suppressed NSCLC cell growth. Consistently with the in vitro studies, mouse xenograft studies validated that miR-1254 suppressed NSCLC tumor growth in vivo. Moreover, we found that HO-1 expression was inversely correlated with miR-1254 level in human NSCLC tumor samples and cell lines. Overall, these findings identify the dual inhibition of HO-1 by miR-1254 as a novel functional mechanism of miRNA, which results in a more effective inhibition of oncogenic mRNA, and leads to a tumor suppressive effect.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Hemo-Oxigenasa 1/biosíntesis , MicroARNs/genética , Factor de Transcripción AP-2/genética , Células A549 , Animales , Apoptosis/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Hemo-Oxigenasa 1/genética , Humanos , Masculino , Ratones , Interferencia de ARN , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Activación Transcripcional/genética , Transfección , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: To evaluate the clinical efficacy of robotic, laparoscopic, and open hemihepatectomy for giant liver haemangiomas. METHODS: From April 2011 to April 2017, consecutive patients who underwent hemihepatectomy for giant liver haemangiomas were included in this study. According to the type of operation, these patients were divided into the robotic hemihepatectomy (RH) group, the laparoscopic hemihepatectomy (LH) group, and the open hemihepatectomy (OH) group. The perioperative and short-term postoperative outcomes were compared among the three groups. The study was reported following the STROCSS criteria. RESULTS: There were no significant differences in age, sex, tumour location, body surface area (BSA), future liver remnant volume (FLR), standard liver volume (SLV), liver haemangioma volume, FLR/SLV, resected normal liver volume/resected volume, hepatic disease, rates of blood transfusion, liver function after 24 h of surgery, operative morbidity and mortality among the three groups. Compared with patients in the RH group (n = 19) and the LH group (n = 13), patients in the OH group (n = 25) had a significantly longer postoperative hospital stay (P < 0.05), time to oral intake (P < 0.05), and time to get-out-of-bed (P < 0.05); a higher VAS score after 24 h of surgery (P < 0.05); and a shorter operative time (P < 0.05). There were no significant differences in these postoperative outcomes (P>0.05) between the RH group and the LH group. When the setup time in the RH group was excluded, the operative time in the RH group was significantly shorter than that in the LH group (P<0.05). There was no significant difference in the operative time between the RH group and the OH group (P>0.05). The amount of intraoperative blood loss in the RH group was the lowest among the three groups (P<0.05), and the amount of intraoperative blood loss in the LH group was less than that in the OH group (P<0.05). CONCLUSION: Robotic and laparoscopic hemihepatectomies were associated with less intraoperative blood loss,better postoperative recovery and lower pain score. Compared with laparoscopic hemihepatectomy, robotic hemihepatectomy was associated with significantly less intraoperative blood loss and a shorter operative time.
Asunto(s)
Hemangioma/cirugía , Hepatectomía/métodos , Laparoscopía/métodos , Neoplasias Hepáticas/cirugía , Adulto , Pérdida de Sangre Quirúrgica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Periodo Posoperatorio , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Purpose of this study was to analyze whether preoperative maximum standardized uptake value (SUVmax) and carbohydrate antigen 19-9 (CA19-9) levels might provide prognostic information in Chinese patients with pancreatic duct adenocarcinoma (PDAC) after pancreaticoduodenectomy (PD). METHODS: Standard PD was performed on 109 patients with PDAC by the same operative team, and all patients received preoperative positron emission tomography/computed tomography examination and blood test. RESULTS: Patients had a mean age of 59 ± 9.35 years. Females accounted for 38.5%. Mean levels of SUVmax, carcino-embryonic antigen (CEA) and CA19-9 were 5.70 ± 2.76, 3.95 ± 4.16ng/mL and 321.62 ± 780.71kU/L. In univariate Logistic regression analysis, preoperative SUVmax, CEA and CA19-9 levels (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly related to AJCC stages. Multivariate Logistic regression analysis showed that preoperative SUVmax and CA19-9 levels (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly associated with AJCC stages. Mean overall survival (OS) was 21 ± 14.50 months. In univariate Cox regression analysis, age, SUVmax, CEA and CA19-9 levels before operation (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly related to OS. Multivariate Cox regression analysis showed that age, SUVmax and CA19-9 levels before operation (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly associated with OS. CONCLUSIONS: This study demonstrated that preoperative SUVmax and CA19-9 levels independently predicted pathological stages and OS of patients with PDAC after PD. These preoperative variables might have significant prognostic implication in patients with PDAC after PD. Patients with abnormal SUVmax and CA19-9 levels should be paid special attention to in operative strategy and perioperative management.
Asunto(s)
Adenocarcinoma/patología , Antígeno CA-19-9/metabolismo , Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/cirugía , Anciano , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/cirugía , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Análisis de SupervivenciaRESUMEN
BACKGROUND: Robotic surgery is increasingly being used in hepatectomy. Previous studies comparing the robotic and laparoscopic minor hepatectomy have been documented, but comparative studies on robotic and laparoscopic hemihepatectomy (LH) involving a large patient cohort are rare. The objective of this study was to compare perioperative outcomes between robotic and LH. METHODS: Data on the demographics, clinicopathologic characteristics, and perioperative outcomes of consecutive patients who underwent robotic or LH in a single center between November 2011 and July 2017 were analyzed. RESULTS: A total of 92 patients underwent robotic and 48 LH. Multiple linear regression analysis showed no significant difference in perioperative outcomes including operative time, postoperative hospital stay, postoperative complications, and mortality between the groups. Compared to the laparoscopic cohort, the robotic cohort had a significantly less estimated blood loss (120.24 mL; 95% confidence interval, 53.72-186.76) and a significantly lower conversation rate (1.09% vs 10.42%; P = .034). Stratified and interaction analyses demonstrated that disease type had an interaction effect on the association between the operative approach and the estimated blood loss. CONCLUSIONS: Robotic hemihepatectomy was safe and feasible in selected patients. It had similar perioperative outcomes as LH and was better than LH regarding estimated blood loss and open conversion.