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Protein succinylation modification is a common post-translational modification (PTM) that plays an important role in bacterial metabolic regulation. In this study, quantitative analysis was conducted on the succinylated proteome of wild-type and florfenicol-resistant Vibrio alginolyticus to investigate the mechanism of succinylation regulating antibiotic resistance. Bioinformatic analysis showed that the differentially succinylated proteins were mainly enriched in energy metabolism, and it was found that the succinylation level of phosphoenolpyruvate carboxyl kinase (PEPCK) was highly expressed in the florfenicol-resistant strain. Site-directed mutagenesis was used to mutate the lysine (K) at the succinylation site of PEPCK to glutamic acid (E) and arginine (R), respectively, to investigate the function of lysine succinylation of PEPCK in the florfenicol resistance of V. alginolyticus. The detection of site-directed mutagenesis strain viability under florfenicol revealed that the survival rate of the E mutant was significantly higher than that of the R mutant and wild type, indicating that succinylation modification of PEPCK protein may affect the resistance of V. alginolyticus to florfenicol. This study indicates the important role of PEPCK during V. alginolyticus antibiotic-resistance evolution and provides a theoretical basis for the prevention and control of vibriosis and the development of new antibiotics.
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Antibacterianos , Farmacorresistência Bacteriana , Lisina , Processamento de Proteína Pós-Traducional , Tianfenicol , Vibrio alginolyticus , Tianfenicol/farmacologia , Tianfenicol/análogos & derivados , Tianfenicol/metabolismo , Vibrio alginolyticus/genética , Vibrio alginolyticus/efeitos dos fármacos , Vibrio alginolyticus/metabolismo , Farmacorresistência Bacteriana/genética , Lisina/metabolismo , Antibacterianos/farmacologia , Mutagênese Sítio-Dirigida , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Ácido Succínico/metabolismo , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Fosfoenolpiruvato Carboxiquinase (ATP)/genéticaRESUMO
BACKGROUND: Little progress has been made in determining the prognostic factors for children and adolescents with high-grade mature B-cell non-Hodgkin lymphoma (HG B-NHL). Based on the important role of body mass index (BMI) in cancer, this study explored the effect of BMI on the prognosis of patients with HG B-NHL. METHODS: Patients aged <18 years with newly diagnosed HG B-NHL were enrolled. Patients were divided into normal, overweight, obese, and emaciated BMI groups according to the growth criteria for children and adolescents. RESULTS: In total, 435 patients were enrolled in this study. There were 329 (75.6%), 46 (10.6%), 13 (3.0%), and 47 (10.8%) patients stratified into the normal, overweight, obese, and emaciated BMI groups, respectively. The event-free survival and overall survival rates of the entire cohort were 89.3% and 92.4%, respectively. The 5-year event-free survival rate for the patients with obese BMI was worse than those with overweight BMI (76.2% vs. 95.6%, p = .04). The 5-year overall survival rate for the patients with emaciated BMI was worse than those with normal (84.5% vs. 93.1%, p = .04) or overweight BMI (84.5% vs. 97.7%, p = .03). Cox multivariate analysis showed that obese or emaciated BMI at diagnosis was associated with an increased risk of death (p = 0.04; HR, 2.26) and was identified as an independent adverse prognostic factor in pediatric HG B-NHL. CONCLUSION: Obese or emaciated BMI at diagnosis is associated with poor prognosis in pediatric HG B-NHL and can be used for risk stratification.
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PURPOSE: The optimal dose and range of radiotherapy for central nervous system (CNS) germinoma have not yet been established. This study aimed to investigate the effects of individualized radiotherapy on the prognosis of patients with germinoma. METHODS: Based on imaging examination, tumor markers, and pathologic results, patients with germinoma received different radiotherapy strategies, including R1 (24 Gy whole ventricular irradiation + tumor-bed boost to 40 Gy), R2 (24-30 Gy craniospinal irradiation + tumor-bed boost to 54 Gy), R3 (24 Gy craniospinal irradiation + tumor-bed boost to 40 Gy), and R4 (30 Gy craniospinal irradiation + tumor-bed boost to 54 Gy with 45 Gy to spinal metastasis). RESULTS: A total of 77 patients were enrolled in this study between January 2015 and March 2021. The 3-year event-free survival (EFS) and overall survival (OS) of the whole cohort were 94.7% ± 2.6% and 96.0% ± 2.3%, respectively. The 3-year EFS for patients with localized and metastatic disease were 96.6% ± 2.4% and 89.2% ± 7.2%, respectively. The 3-year EFS of patients receiving R1, R2, R3, and R4 radiotherapy were 100%, 94.1% ± 5.7%, 100%, and 86.2% ± 9.1%, respectively. CONCLUSION: Good prognosis was still achieved after reducing dose and extent of radiation for the patients who achieved complete response (CR) after induction chemotherapy or pathological CR after second-look surgery.
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Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Germinoma , Humanos , Criança , Adolescente , Estudos Prospectivos , Neoplasias Encefálicas/patologia , Resultado do Tratamento , Neoplasias do Sistema Nervoso Central/radioterapia , Germinoma/patologia , Sistema Nervoso Central/patologia , Dosagem RadioterapêuticaRESUMO
Unmanned Aerial Vehicles (UAVs) can cooperate through formations to perform tasks. Wireless communication allows UAVs to exchange information, but for the situations requiring high security, electromagnetic silence is needed to avoid potential threats. The passive UAV formation maintenance strategies can fulfill the requirement of electromagnetic silence at the cost of heavy real-time computing and precise locations of UAVs. To pursue high real-time performance without the localization of UAVs, this paper proposes a scalable distributed control algorithm for bearing-only passive UAV formation maintenance. By minimizing necessary communication, pure angle information is applied to maintain UAV formations through distributed control, without the knowledge of the UAVs' precise locations. The convergency of the proposed algorithm is proven strictly and the converging radius is derived. Through simulation, the proposed algorithm is proven to be suitable for a general case and demonstrates fast convergence speed, strong anti-interference capability, and high scalability.
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In order to achieve the vision of seamless wireless communication coverage, a space-air-ground integrated network is proposed as a key component of the sixth-generation (6G) mobile communication system. However, the spectrum used by aerial networks has become gradually crowded with the increase in wireless devices. Space networks are also in dire need of developing new bands to address spectrum shortages. As an effective way to solve the spectrum shortage problem, spectrum sharing between aerial/space networks and ground networks has been extensively studied. This article summarizes state-of-the-art studies on spectrum sharing between aerial/space networks and ground networks. First, this article provides an overview of aerial networks and space networks and introduces the main application scenarios of aerial networks and space networks. Then, this article summarizes the spectrum sharing techniques between aerial/space networks and ground networks, including existing spectrum utilization rules, spectrum sharing modes and key technologies. Finally, we summarize the challenges of spectrum sharing between aerial/space networks and ground networks. This article provides guidance for spectrum allocation and spectrum sharing of space-air-ground integrated networks.
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With autonomous driving developing in a booming stage, accurate object detection in complex scenarios attract wide attention to ensure the safety of autonomous driving. Millimeter wave (mmWave) radar and vision fusion is a mainstream solution for accurate obstacle detection. This article presents a detailed survey on mmWave radar and vision fusion based obstacle detection methods. First, we introduce the tasks, evaluation criteria, and datasets of object detection for autonomous driving. The process of mmWave radar and vision fusion is then divided into three parts: sensor deployment, sensor calibration, and sensor fusion, which are reviewed comprehensively. Specifically, we classify the fusion methods into data level, decision level, and feature level fusion methods. In addition, we introduce three-dimensional(3D) object detection, the fusion of lidar and vision in autonomous driving and multimodal information fusion, which are promising for the future. Finally, we summarize this article.
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Condução de Veículo , Radar , Algoritmos , Calibragem , Visão OcularRESUMO
For autonomous driving, it is important to detect obstacles in all scales accurately for safety consideration. In this paper, we propose a new spatial attention fusion (SAF) method for obstacle detection using mmWave radar and vision sensor, where the sparsity of radar points are considered in the proposed SAF. The proposed fusion method can be embedded in the feature-extraction stage, which leverages the features of mmWave radar and vision sensor effectively. Based on the SAF, an attention weight matrix is generated to fuse the vision features, which is different from the concatenation fusion and element-wise add fusion. Moreover, the proposed SAF can be trained by an end-to-end manner incorporated with the recent deep learning object detection framework. In addition, we build a generation model, which converts radar points to radar images for neural network training. Numerical results suggest that the newly developed fusion method achieves superior performance in public benchmarking. In addition, the source code will be released in the GitHub.
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PURPOSE: The optimal dose and range of radiation therapy for central nervous system nongerminomatous germ cell tumors (NGGCTs) have not been uniformly established. Therefore, this study aimed to investigate the effect of individualized radiation therapy, based on the response to induction chemotherapy combined with surgery, on the prognosis of patients with NGGCTs. METHODS AND MATERIALS: Based on the imaging examination and tumor markers after induction chemotherapy and pathologic results of second-look surgery, patients with NGGCT received different radiation therapy strategies, including 30.6 Gy whole ventricular irradiation + tumor-bed boost to 54 Gy, 30.6 Gy craniospinal irradiation + tumor-bed boost to 54 Gy, 36 Gy craniospinal irradiation + tumor-bed boost to 54 Gy, and 36 Gy craniospinal irradiation + 54 Gy tumor-bed boost with 45 Gy to metastatic spinal lesions. RESULTS: A total of 51 patients were enrolled between January 2015 and March 2021, with a median age of 10.3 years. The 3-year event-free survival and overall survival (OS) of the entire cohort were 70.2% ± 6.9% and 77.5% ± 6.0%, respectively. The 3-year OS of patients achieving partial response after induction chemotherapy was higher than that of patients with stable disease (P = .03) or progressive disease (P = .002). The 3-year event-free survival and OS of the 18 patients receiving 30.6 Gy whole ventricular irradiation and 54 Gy tumor-bed boost were 88.9% ± 7.4% and 94.4% ± 5.4%, respectively. CONCLUSIONS: The results suggest that an individualized radiation therapy strategy based on response to induction chemotherapy and surgery is a feasible and promising means of achieving reduction in dose and extent of radiation in patients while still providing good response.
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Neoplasias do Sistema Nervoso Central , Quimioterapia de Indução , Neoplasias Embrionárias de Células Germinativas , Humanos , Neoplasias Embrionárias de Células Germinativas/radioterapia , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Adolescente , Criança , Masculino , Estudos Prospectivos , Pré-Escolar , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/patologia , Resultado do Tratamento , Feminino , Radiação Cranioespinal/métodos , Dosagem Radioterapêutica , Neoplasias Testiculares/radioterapia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/mortalidade , Intervalo Livre de ProgressãoRESUMO
A novel breast ultrasound tomography system based on a circular array of capacitive micromechanical ultrasound transducers (CMUT) has broad application prospects. However, the images produced by this system are not suitable as input for the training phase of the super-resolution (SR) reconstruction algorithm. To solve the problem, this paper proposes an improved medical image super-resolution (MeSR) method based on the sparse domain. First, we use the simultaneous algebraic reconstruction technique (SART) with high imaging accuracy to reconstruct the image into a training image in a sparse domain model. Secondly, we denoise and enhance the contrast of the SART images to obtain improved detail images before training the dictionary. Then, we use the original detail image as the guide image to further process the improved detail image. Therefore, a high-precision dictionary was obtained during the testing phase and applied to filtered back projection SR reconstruction. We compared the proposed algorithm with previously reported algorithms in the Shepp Logan model and the model based on the CMUT background. The results showed significant improvements in peak signal-to-noise ratio, entropy, and average gradient compared to previously reported algorithms. The experimental results demonstrated that the proposed MeSR method can use noisy reconstructed images as input for the training phase of the SR algorithm and produce excellent visual effects.
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Mama , Ultrassonografia Mamária , Ultrassonografia Mamária/métodos , Algoritmos , Humanos , Feminino , Mama/diagnóstico por imagemRESUMO
Lysine acetylation modification is a dynamic and reversible post-translational modification, which plays an important role in the metabolism and pathogenicity of pathogenic bacteria. Vibrio alginolyticus is a common pathogenic bacterium in aquaculture, and bile salt can trigger the expression of bacterial virulence. However, little is known about the function of lysine acetylation in V. alginolyticus under bile salt stress. In this study, 1,315 acetylated peptides on 689 proteins were identified in V. alginolyticus under bile salt stress by acetyl-lysine antibody enrichment and high-resolution mass spectrometry. Bioinformatics analysis found that the peptides motif ****A*Kac**** and *******Kac****A* were highly conserved, and protein lysine acetylation was involved in regulating various cellular biological processes and maintaining the normal life activities of bacteria, such as ribosome, aminoacyl-tRNA biosynthesis, fatty acid metabolism, two-component system, and bacterial secretion system. Further, 22 acetylated proteins were also found to be related to the virulence of V. alginolyticus under bile salt stress through secretion system, chemotaxis and motility, and adherence. Finally, comparing un-treated and treated with bile salt stress lysine acetylated proteins, it was found that there were 240 overlapping proteins, and found amino sugar and nucleotide sugar metabolism, beta-Lactam resistance, fatty acid degradation, carbon metabolism, and microbial metabolism in diverse environments pathways were significantly enriched in bile salt stress alone. In conclusion, this study is a holistic analysis of lysine acetylation in V. alginolyticus under bile salt stress, especially many virulence factors have also acetylated.
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BACKGROUND: Ringer's ethyl pyruvate solution (REPS) has been shown to ameliorate liver injury in a murine model of extrahepatic cholestasis. The goal of the present investigation was to gain additional information about whether infusing REPS instead of Ringer's lactate solution (RLS) after inducing obstructive jaundice would be beneficial to intestinal barrier function, inflammatory response, and oxidative stress. METHODS: Male Sprague Dawley rats were divided into three groups: Group Sham (n=6), sham-treated controls; Group RLS (n=9), common bile duct ligation (CBDL) plus RLS; and Group REPS (n=9), CBDL plus REPS. On 14 d after BDL, the rats were sacrificed and intestinal permeability was analyzed. Ileal IL-6 and TNF-alpha levels, malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), and NF-kappaB activity were determined. Histologic examination and apoptosis of ileum were also examined. RESULTS: Relative to sham-treated controls, CBDL in RLS-treated rats were associated with increased intestinal permeability to FITC-labeled dextran (4.51+/-0.85 versus 0.44+/-0.18, P<0.01), histopathologic damage and apoptosis (68.4+/-13.4 versus 6.7+/-1.9 pre-1000 villi cells, P<0.01). IL-6 and TNF-alpha level, MDA, MPO, and NF-kappaB activity in ileal tissues were also promoted, along with decreased GSH levels. Treatment with REPS significantly decreased intestinal permeability (3.37+/-0.71, P<0.01) and apoptosis (42.8+/-14.3 pre-1000 villi cells, P<0.01). Other changes were also significantly attenuated by treatment with REPS after CBDL. CONCLUSIONS: The present study demonstrates that administration of REPS, but not RLS, maintains intestinal barrier function and reduces intestinal oxidative damage, inflammatory response, and apoptosis in cholestatic rats. This effect of ethyl pyruvate may be useful for preventing intestinal injury in patients with biliary obstruction.
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Colestase Extra-Hepática/tratamento farmacológico , Enterite/tratamento farmacológico , Icterícia Obstrutiva/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Piruvatos/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Colestase Extra-Hepática/imunologia , Colestase Extra-Hepática/patologia , Modelos Animais de Doenças , Enterite/imunologia , Enterite/patologia , Glutationa/metabolismo , Íleo/metabolismo , Íleo/patologia , Interleucina-6/metabolismo , Absorção Intestinal/efeitos dos fármacos , Icterícia Obstrutiva/imunologia , Icterícia Obstrutiva/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , gama-Glutamiltransferase/sangueRESUMO
BACKGROUND: This study investigates the clinical outcomes of endovenous microwave ablation and endovenous laser ablation for varicose veins. METHODS: A total of 139 patients who underwent endovenous microwave ablation and 145 patients who underwent endovenous laser ablation were included in this multicenter study. The clinical outcomes and complications were assessed at 1, 6, and 12 months after the procedure. The effect on quality of life was assessed by the Aberdeen Varicose Vein Questionnaire and the EuroQol Group 5-Dimension Self-Report Questionnaire. RESULTS: The endovenous microwave ablation group had a shorter procedure time than the endovenous laser ablation group (42.58 ± 15.62 minutes vs 65.46 ± 24.38 minutes, P < .01), and no significant differences were observed in the other procedure parameters. The incidences of induration (20.26% vs 31.06%) and ecchymosis (13.07% vs 22.98%, P < .05) were lower in the endovenous microwave ablation group. The rates of temporary paresthesia (9.80% vs 18.01%) and residual varicosities (8.61% vs 16.77%, P < .05) were lower in the endovenous microwave ablation group at 1 month. There were no significant differences in paresthesia or saphenous vein closure rates between the groups at 6 and 12 months. Both groups had signiï¬cant improvements in their Aberdeen Varicose Vein Questionnaire and EuroQol Group 5-Dimension Self-Report Questionnaire scores post-procedure, and no signiï¬cant differences in Aberdeen Varicose Vein Questionnaire and EuroQol Group 5-Dimension Self-Report Questionnaire scores were confirmed. However, local recurrence below the knee was lower in the endovenous microwave ablation group (2.34% vs 8.46%, P < .05) after 12 months. CONCLUSION: Our results confirmed that the endovenous microwave ablation procedure demonstrated a shorter procedure time, lower complication, and local recurrence than the endovenous laser ablation procedure.
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Técnicas de Ablação/métodos , Terapia a Laser/métodos , Micro-Ondas/uso terapêutico , Varizes/cirurgia , Técnicas de Ablação/efeitos adversos , Adulto , Feminino , Seguimentos , Humanos , Terapia a Laser/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Varizes/psicologiaRESUMO
To overcome shortcomings of current small-diameter vascular prostheses, we developed a novel allogenic vascular graft from a decellularized scaffold modified through heparin immobilization and vascular endothelial growth factor (VEGF) coating. The VEGF coating and release profiles were assayed by enzyme-linked immunosorbent assay, the biological activity of modified surface was validated by human umbilical vein endothelial cells seeding and proliferation for 10 days in vitro. In vivo, we implanted either a modified or a nonmodified scaffold as bilateral carotid allogenic graft in canines (n = 15). The morphological examination of decellularized scaffolds showed complete removal of cellular components while the extracellular matrix structure remained intact. After modification, the scaffolds possessed local sustained release of VEGF up to 20 days, on which the cells cultured showed significantly higher proliferation rate throughout the time after incubation compared with the cells cultured on nonmodified scaffolds (P < 0.0001). After 6 months of implantation, the luminal surfaces of modified scaffolds exhibited complete endothelium regeneration, however, only a few disorderly cells and thrombosis overlay the luminal surfaces of nonmodified scaffolds. Specifically, the modified scaffolds exhibited significantly smaller hyperplastic neointima area compared with the nonmodified, not only at midportion (0.56 +/- 0.07 vs. 2.04 +/- 0.12 mm(2), P < 0.0001), but also at anastomotic sites (1.76 +/- 0.12 vs. 3.67 +/- 0.20 mm(2), P < 0.0001). Moreover, modified scaffolds had a significantly higher patency rate than the nonmodified after 6 months of implantation (14/15 vs. 7/15, P = 0.005). Overall, this modified decellularized scaffold provides a promising direction for fabrication of small-diameter vascular grafts.
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Prótese Vascular , Heparina/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Fator A de Crescimento do Endotélio Vascular/química , Animais , Implante de Prótese Vascular , Proliferação de Células , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/metabolismo , Cães , Células Endoteliais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Grau de Desobstrução VascularRESUMO
The aim of this study was to explore whether reward learning would affect the processing of targets when an emotional stimulus was task irrelevant. In the current study, using a visual search paradigm to establish an association between emotional faces and reward, an emotional face appeared as a task-irrelevant distractor during the test after reward learning, and participants were asked to judge the orientation of a line on the face. In experiment 1, no significant difference was found between the high reward-fear distractor condition and the no reward-neutral condition, but the response times of the high reward-fear condition were significantly longer than those of the low reward-happy condition. In experiment 2, there was no significant difference in participants' performance between high reward-happy and no reward-neutral responses. In addition, response times of the low reward-fear condition wear significantly longer than those of the high reward-happy and no reward-neutral conditions. The results show that reward learning affects attention bias of task-irrelevant emotional faces even when reward is absent. Moreover, the high reward selection history is more effective in weakening the emotional advantage of the processing advantage than the low reward.
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A 67-year-old man who received endoscopic submucosal dissection for an early squamous esophageal cancer was hospitalized for dysphagia. The mucosal defect was over three quarters of the circumference, and the distal edge of the resection scar formed the stenosis after 8 months. After experiencing conservative treatment, probe expansion, and esophageal stent placement, the symptom of deglutition disorder in the patient was improved, but persistent hemorrhage and progressive anemia occurred in the short term. An enhanced neck and chest computed tomography (CT) showed a contrast agent leaked from the aberrant right subclavian artery to the esophagus. A pseudoaneurysm of the aberrant right subclavian artery and subclavian artery-esophageal fistula were diagnosed by CT angiography. Although false aneurysms developing after iatrogenic injury and trauma have been reported, those caused by esophageal stent placement because of esophageal stricture after endoscopic submucosal dissection have not. When persistent hemorrhage and progressive anemia develop after esophageal stent placement, an enhanced CT should be performed to exclude the false aneurysm.
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Falso Aneurisma/etiologia , Anormalidades Cardiovasculares , Ressecção Endoscópica de Mucosa/métodos , Estenose Esofágica/cirurgia , Esofagoscopia/métodos , Stents/efeitos adversos , Artéria Subclávia/anormalidades , Idoso , Anemia/diagnóstico por imagem , Anemia/etiologia , Falso Aneurisma/diagnóstico por imagem , Ressecção Endoscópica de Mucosa/instrumentação , Fístula Esofágica/diagnóstico por imagem , Fístula Esofágica/etiologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Fístula Vascular/diagnóstico por imagem , Fístula Vascular/etiologiaRESUMO
The inflammatory response plays a vital role in cerebral aneurysm (CA) formation and progression. Tanshinone IIA (Tan IIA) is one of the major active components of Chinese medicine Danshen (Salvia miltiorrhiza Bunge) and is widely used for the treatment of cardiovascular diseases, due to its antiinflammatory effects. The aim of the present study was to investigate whether Tan IIA can attenuate CA formation in rat models, and determine its underlying mechanisms. CAs were induced in rats surgically and through highsalt diet treatments. The Tan IIAtreated group displayed relatively mild symptoms, as compared with the control group. Tan IIA treatment reduced macrophage infiltration and nuclear factor (NF)κB activation in aneurysmal walls. Next, lipopolysaccharide (LPS)stimulated RAW 264.7 murine macrophage cells were used to examine the antiinflammatory effects of Tan IIA on macrophages. It was found that Tan IIA reversed LPSinduced differentiation of RAW 264.7 cells and suppressed NFκB pathway activation. In conclusion, these findings demonstrated that Tan IIA can suppress CA formation by inhibiting inflammatory responses in macrophages.
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Abietanos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Aneurisma Intracraniano/tratamento farmacológico , NF-kappa B/imunologia , Animais , Aneurisma Intracraniano/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Células RAW 264.7 , Ratos Sprague-Dawley , Salvia miltiorrhizaRESUMO
In mammals, female fecundity is determined by the size of the primordial follicle (PF) pool, which is established during the perinatal period. As a non-renewable resource, the preservation of dormant PFs is crucial for sustaining female reproduction throughout life. Although studies have revealed that several oocyte-derived functional genes and pathways, such as newborn ovary homeobox (NOBOX) and 3-phosphoinositide-dependent protein kinase-1, participate in maintaining the PF pool, our understanding of the underlying molecular mechanisms is still incomplete. Here, we demonstrate that E-cadherin (E-cad) plays a crucial role in the maintenance of PFs in mice. E-cad is specifically localized to the cytomembrane of oocytes in PFs. Knockdown of E-cad in neonatal ovaries resulted in significant PF loss owing to oocyte apoptosis. In addition, the expression pattern of NOBOX is similar to that of E-cad. Knockdown of E-cad resulted in a decreased NOBOX level, whereas overexpression of Nobox partially rescued the follicle loss induced by silencing E-cad. Furthermore, E-cad governed NOBOX expression by regulating the shuttle protein, ß-catenin, which acts as a transcriptional co-activator. Notably, E-cad, which is a transmembrane protein expressed in the oocytes, was also responsible for maintaining the PF structure by facilitating cell-cell adhesive contacts with surrounding pregranulosa cells. In conclusion, E-cad in oocytes of PFs plays an indispensable role in the maintenance of the PF pool by facilitating follicular structural stability and regulating NOBOX expression. These findings shed light on the physiology of sustaining female reproduction.
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Caderinas/genética , Caderinas/metabolismo , Fertilidade/fisiologia , Oócitos/metabolismo , Folículo Ovariano/metabolismo , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/genética , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Camundongos , Gravidez , RNA Interferente Pequeno/genética , Fatores de Transcrição/metabolismo , Transfecção , beta Catenina/metabolismoRESUMO
Lanosterol 14 α-demethylase (CYP51) plays a crucial role in cholesterol biosynthesis. In gamete development, CYP51 is involved in initiating meiosis resumption in oocytes through its product, meiosis activating sterol (MAS). In this study, CYP51 was observed to localize within the nucleus of germ cells undergoing meiotic prophase I. Following the addition of retinoic acid (RA) to induce meiosis or the RA receptor pan-antagonist AGN193109 to block meiosis in fetal ovaries, the translocation of CYP51 into the nucleus of oocytes was advanced or delayed, respectively. In addition, treatment with Cyp51-siRNA or RS21745, a specific CYP51 inhibitor, significantly delayed the meiotic progression of oocytes in the ovary, with most oocytes arresting at the zygotene stage, and likewise, significantly reduced perinatal primordial follicle formation. Furthermore, inhibition of CYP51 is correlated to significantly decreased expression of REC8 and STAG3, both of which are meiosis-specific cohesin subunits. To sum up, RA-induced CYP51 nuclear translocation is critical for oocytes meiotic progression, and consequently folliculogenesis, which might act through impacting the expression of meiosis-specific cohesins REC8 and STAG3.
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Gap junctions (GJs) are indispensable for communication between cumulus cells (CCs) and oocytes in coordinating the gonadotropin-induced meiotic maturation of oocytes. Of all proteins that constitute GJs, phosphorylated connexin43 (pCx43) is vital for mediating the actions of gonadotropins. In this study, the mechanism of Cx43 phosphorylation in response to follicle stimulating hormone (FSH) stimulation was examined using an in vitro model of mouse cumulus-oocyte complexes (COCs). The results confirmed that Cx43 phosphorylation occurred twice during FSH treatment. Importantly, the second Cx43 phosphorylation was closely related to cAMP level reduction within oocytes, which initiated oocyte maturation. Exploration of the underlying mechanism revealed that the CC-specific protein kinase C ε (PKCε) level was upregulated by FSH stimulation. PKCε was a kinase downstream from mitogen-activated protein kinase (MAPK) and was responsible for Cx43 phosphorylation. Interestingly, MAPK was involved in both Cx43 phosphorylation processes, while PKCε was only involved in the second. In conclusion, PKCε-mediated MAPK signals might contribute to Cx43 phosphorylation in CCs during FSH-induced oocyte meiotic resumption. Our findings contribute to a better understanding of the molecular regulation mechanism of oocyte maturation in response to FSH in vitro.
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OBJECTIVE: To evaluate the immediate and mid-term effectiveness of hybrid procedures (combined open surgery and endovascular therapy) for multilerel femoral and popliteal artery occlusive disease. METHODS: Between June 2009 and June 2012, 22 cases of severe femoral and popliteal artery occlusive disease were treated by hybrid surgery. There were 15 men and 7 women with an age range of 52-78 years (mean, 66.2 years) and with a disease duration of 6 months to 5 years (mean, 1.5 years). Of 22 patients, 13 had a history of smoking; 8 were classified as Fontaine III and 14 as Fontaine IV. The complications included diabetes (8 patients), hypertension (16 patients), hyperlipemia (10 patients), coronary heart disease (11 patients), and chronic kidney failure (1 patient). Patency analyses were performed using Kaplan-Meier life tables and log-rank test. RESULTS: All patients underwent successfully procedures. The time of operation was 70-160 minutes (mean, 137 minutes). Acute myocardial infarction, hematoma of incision, fracture of stent, and stent thrombosis occurred in 1 case, respectively. At 6 months after surgery, the ankle brachial index (ABI), the transcutaneous oxygen pressure (TcpO2), and the average intermittent claudication distance were significantly increased when compared with preoperative ones [0.79 +/- 0.33 versus 0.32 +/- 0.18, (42.7 +/- 15.7) kPa versus (17.6 +/- 11.6) kPa, and (420 +/- 80) m versus (160 +/- 54) m, P < 0.05]. The patients were followed up 6-24 months (mean, 14.5 months). The primary patency rate, primary assisted patency rate, and second patency rate were 77.3% (17/22), 90.9% (20/22), and 95.5% (21/22) respectively, showing no significant difference among them (P > 0.05). No significant difference was found in various-stage patency rates between patients at Fontaine III and IV (P > 0.05). CONCLUSION: Hybrid procedures provide an effective treatment of multilevel femoral artery and popliteal artery disease while there is good outflow.