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1.
J Neurosci Methods ; 365: 109383, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34634283

RESUMO

BACKGROUND: Single-element focused transducers applied in blood-brain barrier (BBB) disruption experiments to optimize intravascular therapies in CNS diseases have the advantage of low cost and portability. Most of the in vivo studies on non-human primates report the use of single-element transducers with an annular spherical shape and a central frequency of 500 kHz. High-frequency ultrasound has smaller focal area and less standing-wave effect but lower transcranial penetration efficiency. Our study reports the feasibility and safety concerns of BBB opening by single-element spherical transducers with central frequencies of 300, 650 and 800 kHz on two rhesus macaques. METHODS: Pulsed ultrasound exposure (3-minute duration, 0.5-1% duty cycle) combined with microbubble injection (SonoVue, 0.2uL/g) was used to disrupt the BBB of the monkeys under the magnetic resonance imaging (MRI) guidance. Gadolinium contrast-enhanced MRI was used to confirm and evaluate the BBB opening after sonication. T2-weighted fast spin echo and T2 * -weighted gradient echo sequences were used to check the post-sonication complications, such as edema and micro-bleeding. RESULTS: Contrast enhancement was found on the post-sonication T1 weighted images for all experiments, showing that the BBB was successfully opened under all the three frequencies on both monkeys. The enhanced area was largest at the lowest frequency. No obvious hypo-intensity or hyper-intensity was observed on either the T2 * weighted gradient echo images or T2-weighted fast-spin echo images, implying the safety of the opening procedure. However, signal enhancement was also observed in the subarachnoid space of the sulci for all frequencies, indicating that the BBB was also disrupted in the propagation path outside the focal area. CONCLUSIONS: The feasibility of BBB opening with single-element transducer under frequencies ranging from 300 kHz to 800 kHz was confirmed by experiments in two non-human primates in vivo. Further investigation into the off-target effects and transducer configurations is needed for safety optimization.

2.
Front Oncol ; 11: 765378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722320

RESUMO

Background/Objective: We aimed to compare the 10-year survival outcomes of induction docetaxel plus cisplatin and 5-fluorouracil (TPF), docetaxel plus cisplatin (TP), and cisplatin plus 5-fluorouracil (PF) regimens additional to concurrent chemoradiotherapy (CRT) in locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: Eligible patients with newly diagnosed stage III-IVA NPC were included. Propensity score matching (PSM) was used to balance prognostic covariates. Survival outcomes and toxicities between different groups were compared. Results: A total of 855 patients between 2009 and 2012 were included, with 395 (46.2%), 258 (30.2%), and 202 (23.6%) receiving TPF plus CRT, TP plus CRT, and PF plus CRT regimens, respectively. After a median follow-up of 111.8 months, multivariate analysis both in the whole cohort and PSM selected 202 pairs showed that TPF plus CRT and TP plus CRT achieved significantly better 10-year overall survival (OS) than PF plus CRT. Sensitivity analysis after excluding patients with T3-4N0 disease demonstrated that TPF plus CRT still achieved significantly better OS than PF plus CRT (HR, 0.580; 95% CI, 0.395-0.852; P = 0.005), while the difference between TP plus CRT and PF plus CRT was marginally significant (HR, 0.712; 95% CI, 0.503-1.008; P = 0.056). With regard to toxicity profile, PF regimen achieved the lowest grade 3-5 toxicities (27.3%). Conclusion: TPF plus CRT and TP plus CRT were better than PF plus CRT in improving the 10-year OS of patients with stage III-IVA NPC.

3.
Small ; : e2104073, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725921

RESUMO

The design and characterization of purely organic room-temperature phosphorescent (RTP) materials for optoelectronic applications is currently the focus of research in the field of organic electronics. Particularly, with the merits of preparation controllability and modulation flexibility, host-guest material systems are encouraging candidates that can prepare high-performance RTP materials. By regulating the interaction between host and guest molecules, it can effectively control the quantum efficiency, luminescent lifetime, and color of host-guest RTP materials, and even produce RTP emission with stimuli-responsive features, holding tremendous potential in diverse applications such as encryption and anti-counterfeiting, organic light-emitting diodes, sensing, optical recording, etc. Here a roundup of rapid achievement in construction strategies, molecule systems, and diversity of applications of host-guest material systems is outlined. Intrinsic correlations between the molecular properties and a survey of recent significant advances in the development of host-guest RTP materials divided into three systems including rigid matrix, exciplex, and sensitization are presented. Providing an insightful understanding of host-guest RTP materials and offering a promising platform for high throughput screening of RTP systems with inherent advantages of simple material preparation, low-cost, versatile resource, and controllably modulated properties for a wide range of applications is intended.

4.
Biomed Phys Eng Express ; 8(1)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34768245

RESUMO

Online dose verification in proton therapy is a critical task for quality assurance. We further studied the feasibility of using a wavelet-based machine learning framework to accomplishing that goal in three dimensions, built upon our previous work in 1D. The wavelet decomposition was utilized to extract features of acoustic signals and a bidirectional long-short-term memory (Bi-LSTM) recurrent neural network (RNN) was used. The 3D dose distributions of mono-energetic proton beams (multiple beam energies) inside a 3D CT phantom, were generated using Monte-Carlo simulation. The 3D propagation of acoustic signal was modeled using the k-Wave toolbox. Three different beamlets (i.e. acoustic pathways) were tested, one with its own model. The performance was quantitatively evaluated in terms of mean relative error (MRE) of dose distribution and positioning error of Bragg peak (ΔBP), for two signal-to-noise ratios (SNRs). Due to the lack of experimental data for the time being, two SNR conditions were modeled (SNR = 1 and 5). The model is found to yield good accuracy and noise immunity for all three beamlets. The results exhibit an MRE below 0.6% (without noise) and 1.2% (SNR = 5), andΔBPbelow 1.2 mm (without noise) and 1.3 mm (SNR = 5). For the worst-case scenario (SNR = 1), the MRE andΔBPare below 2.3% and 1.9 mm, respectively. It is encouraging to find out that our model is able to identify the correlation between acoustic waveforms and dose distributions in 3D heterogeneous tissues, as in the 1D case. The work lays a good foundation for us to advance the study and fully validate the feasibility with experimental results.

5.
J Anat ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642936

RESUMO

Sex differences in behaviour partly arise from the sexual dimorphism of brain anatomy between males and females. However, the sexual dimorphism of the tree shrew brain is unclear. In the present study, we examined the detailed distribution of vasoactive intestinal polypeptide-immunoreactive (VIP-ir) neurons and fibres in the suprachiasmatic nucleus (SCN) and VIP-ir fibres in the bed nucleus of the stria terminalis (BST) of male and female tree shrews. The overall volume of the SCN in male tree shrews was comparable with that in females. However, males showed a significantly higher density of VIP-ir cells and fibres in the SCN than females. The shape of the VIP-stained area in coronal sections was arched, elongated or oval in the lateral division (STL) and the anterior part of the medial division (STMA) of the BST and oval or round in the posterior part of the medial division of the BST (STMP). The volume of the VIP-stained BST in male tree shrews was similar to that in females. The overall distribution of VIP-ir fibres was similar between the sexes throughout the BST except within the STMA, where darkly stained fibres were observed in males, whereas lightly stained fibres were observed in females. Furthermore, male tree shrews showed a significantly higher intensity of Nissl staining in the medial preoptic area (MPA) and the ventral part of the medial division of the BST than females. These findings are the first to reveal sexual dimorphism in the SCN, BST and MPA of the tree shrew brain, providing neuroanatomical evidence of sexual dimorphism in these regions related to their roles in sex differences in physiology and behaviour.

6.
Pharmacotherapy ; 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655497

RESUMO

STUDY OBJECTIVES: This study aimed to establish a population pharmacokinetic (PPK) model of intravenous voriconazole (VRC) in critically ill patients with liver dysfunction and to explore the optimal dosing strategies in specific clinical scenarios for invasive fungal infections (IFIs) caused by common Aspergillus and Candida species. DESIGN: Prospective pharmacokinetics study. SETTING: The intensive care unit in a tertiary-care medical center. PATIENTS: A total of 297 plasma VRC concentrations from 26 critically ill patients with liver dysfunction were included in the PPK analysis. METHODS: Model-based simulations with therapeutic range of 2-6 mg/L as the plasma trough concentration (Cmin ) target and the free area under the concentration-time curve from 0 to 24 h (ƒAUC24 ) divided by the minimum inhibitory concentration (MIC) (ie, ƒAUC24 /MIC) ≥25 as the effective target were performed to optimize VRC dosing regimens for Child-Pugh class A and B (CP-A/B) and Child-Pugh class C (CP-C) patients. RESULTS: A two-compartment model with first-order elimination adequately described the data. Significant covariates in the final model were body weight on both central and peripheral distribution volume and Child-Pugh class on clearance. Intravenous VRC loading dose of 5 mg/kg every 12 h (q12h) for the first day was adequate for CP-A/B and CP-C patients to attain the Cmin target at 24 h. The maintenance dose regimens of 100 mg q12h or 200 mg q24h for CP-A/B patients and 50 mg q12h or 100 mg q24h for CP-C patients could obtain the probability of effective target attainment of >90% at an MIC ≤0.5 mg/L and achieve the cumulative fraction of response of >90% against C. albicans, C. parapsilosis, C. glabrata, C. krusei, A. fumigatus, and A. flavus. Additionally, the daily VRC doses could be increased by 50 mg for CP-A/B and CP-C patients at an MIC of 1 mg/L, with plasma Cmin monitored closely to avoid serious adverse events. It is recommended that an appropriate alternative antifungal agent or a combination therapy could be adopted when an MIC ≥2 mg/L is reported, or when the infection is caused by C. tropicalis but the MIC value is not available. CONCLUSIONS: For critically ill patients with liver dysfunction, the loading dose of intravenous VRC should be reduced to 5 mg/kg q12h. Additionally, based on the types of fungal pathogens and their susceptibility to VRC, the adjusted maintenance dose regimens with lower doses or longer dosing intervals should be considered for CP-A/B and CP-C patients.

7.
ACS Omega ; 6(41): 27478-27484, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34693168

RESUMO

This paper focused on the oxidation-alkaline extraction process of vanadium-chromium-reducing residue. The affected parameters including reaction temperature, KMnO4 dosage, reaction time, NaOH dosage, and liquid-to-solid ratio on the extraction process were investigated. The E-pH diagram and the thermodynamic analysis indicated that KMnO4 was suitable for the oxidation of low-valence vanadium and chromium. Vanadium (97.24%) and chromium (56.20%) were extracted under the following optimal reaction conditions: reaction temperature of 90 °C, reaction time of 90 min, dosage of KMnO4 at m(KMnO4)/m(residue) = 0.40, dosage of NaOH at m(NaOH)/m(residue) = 0.30, and liquid-to-solid ratio at 5:1 mL/g. The extraction process of vanadium was controlled by the reactant through the solid product layer and the extraction kinetics behavior fitted well with the shrink core model with an E a of 15.37 kJ/mol. At the same time, the surface chemical reaction was the controlling step for chromium extraction, which was difficult with an E a of 39.78 kJ/mol.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34714751

RESUMO

Recently, large volumes of false or unverified information (e.g., fake news and rumors) appear frequently in emerging social media, which are often discussed on a large scale and widely disseminated, causing bad consequences. Many studies on rumor detection indicate that the stance distribution of posts is closely related to the rumor veracity. However, these two tasks are generally considered separately or just using a shared encoder/layer via multitask learning, without exploring the more profound correlation between them. In particular, the performance of existing methods relies heavily on the quality of hand-crafted features and the quantity of labeled data, which is not conducive to early rumor detection and few-shot detection. In this article, we construct a hierarchical heterogeneous graph by associating posts containing the same high-frequency words to facilitate the feature cross-topic propagation and jointly formulate stance and rumor detection as multistage classification tasks. To realize the updating of node embeddings jointly driven by stance and rumor detection, we propose a multigraph neural network framework, which can more flexibly capture the attribute and structure information of the context. Experiments on real datasets collected from Twitter and Reddit show that our method outperforms state-of-the-art by a large margin on both stance and rumor detection. And the experimental results also show that our method has better interpretability and requires less labeled data.

9.
Bioengineered ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709968

RESUMO

Circular RNA (circRNA) presents an essential regulatory role in affecting the occurrence and acquired resistance in non-small cell lung cancer (NSCLC), but how circSOX13 impacts NSCLC is unclear. In this work it was found that compared with adjacent normal tissues, circSOX13 and the microtubule-associated protein RP/EB family member 1 (MAPRE1) were signally up-regulated in NSCLC while miR-3194-3p was signally lowered. Pulmonary function tests (PETs) revealed that knocking down circSOX13 or overexpressing miR-3194-3p inhibited NSCLC proliferation, invasion and migration but promoted its apoptosis. The promoting effect of overexpressing circSOX13 on NSCLC was reversed via knocking down MAPRE1. Additionally, knocking down circSOX13 reduced cisplatin resistance in NSCLC. Furthermore, circSOX13 mediated MAPRE1 expression via competitively binding miR-3194-3p to exert its tumorigenic impact. To conclude, this work clarified the carcinogenic impact of circSOX13-miR-3194-3p-MAPRE1 axis on NSCLC and DDP resistance. CircSOX13 can be a potential diagnostic marker and therapeutic target for NSCLC, thus providing a new insight for clinically reversing its acquired resistance.

10.
Risk Manag Healthc Policy ; 14: 4063-4072, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616193

RESUMO

Purpose: Sleep duration was associated with large artery atherosclerosis, but its association with atherosclerosis in lower extremity arteries was not well studied. Together with sleep, physical activity constitutes main component of our daily life and influences sleep. Here, we aimed to examine the independent and joint associations of sleep duration and physical activity with peripheral artery disease (PAD) in Chinese adults. Patients and Methods: In Tianning cohort, night-time sleep duration and physical activity were assessed by the Pittsburgh Sleep Quality Index and the Global Physical Activity Questionnaire, respectively, for 5130 participants (51.0±15.6 years, 58.7% female). PAD was defined as ankle-brachial index (ABI) <0.9. General linear, and logistic regression models were used to assess the associations of sleep duration and physical activity with PAD. The biological interaction between sleep duration and physical activity on PAD was examined using additive model. Results: Compared to participants sleeping 6-8.9 h, those sleeping ≥9 h had a 0.02 lower ABI (ß=-0.02, P=0.007) and 38% higher odds of PAD (OR=1.38, P=0.035). Compared to physically active participants sleeping 6-8.9 h, among ≥9 h group, physically inactive individuals had significantly increased odds of PAD (OR=2.40, P<0.001), whereas physically active individuals did not (OR=1.15, P=0.472). On additive scale, attributable proportion due to interaction (0.40, 95% CI: 0.07, 0.73) indicated a significant interaction between sleep duration and physical activity on PAD. Conclusion: Being physically active may attenuate the detrimental association between prolonged sleep duration and PAD. Moreover, we found a significant interaction between prolonged sleep duration and physical inactivity in the prevalence of PAD.

11.
Cell Death Discov ; 7(1): 298, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663798

RESUMO

The increasing incidence of hepatocellular carcinoma (HCC) is of great concern globally, but the molecular pathogenesis of these tumors remains unclear. Sorafenib is a first-line drug for the treatment of advanced HCC. However, the efficacy of sorafenib in improving patient survival is limited, and most patients inevitably develop resistance to this drug. Recent studies have demonstrated that the activation of the IRE1α-XBP1s pathway might play a protective role in the response to sorafenib and contribute to malignancy in HCC. Here, we found that RCN1, an endoplasmic reticulum resident protein, is significantly upregulated in sorafenib-resistant HCC cells and promotes tumor progression. Our analysis showed that RCN1 may be an independent predictor of tumor recurrence and overall survival. Mechanistically, RCN1 promotes the dissociation of GRP78 from IRE1α in sorafenib-resistant cells by interacting with GRP78 through its EFh1/2 domain. Subsequently, the IRE1α-XBP1s pathway, a branch of the unfolded protein response, is sustainably activated. Interestingly, IRE1α-XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in HCC. These results suggest that RCN1-targeted therapy might be a feasible strategy for the treatment of HCC.

12.
Front Nutr ; 8: 739359, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616766

RESUMO

Objective: The results from epidemiologic studies on the relationship between intake of coffee and the risk of gestational diabetes mellitus (GDM) remain inconclusive. A meta-analysis was performed to achieve a comprehensive finding regarding the association between intake of coffee and the risk of GDM. Methods: PubMed, Scopus, ISI Web of Science, and Google Scholar were searched to find articles published up to August 2021. Observational studies that reported risk estimates [risk ratios (RRs), hazard ratios (HRs), and odds ratios (ORs)] for the association of consumption of coffee with the risk of GDM in pregnant women were included. Random effects model was applied to calculate summarized risk estimate and 95% CIs for the highest vs. lowest categories of intake of coffee. Results: Seven observational studies (three cohort, two case-control, and two cross-sectional studies) with 75,607 participants and 1,625 women with GDM met the inclusion criteria. The meta-analysis of comparing the highest vs. lowest intake of coffee categories showed no significant association between intake of coffee and risk of GDM (summarized risk estimate: 0.89; 95% CI: 0.76, 1.05; I 2 = 63.4%). Subgroup analysis showed that consumption of coffee had an inverse relationship with GDM in studies conducted in non-Asia countries (summarized risk estimate: 0.75; 95% CI: 0.58, 0.97; I 2 = 6%). Conclusion: This study has shown that high consumption of coffee did not decrease the risk of GDM. Furthermore, large-scale cohort studies are required to confirm our findings.

13.
Curr Med Sci ; 41(5): 909-915, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34689292

RESUMO

OBJECTIVE: To evaluate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on preventing rats from glucocorticoid-induced osteonecrosis of femoral head (GCONFH) in the early stage in vivo and to investigate the possible mechanism of hUC-MSCs in regulating the balance of osteogenesis and adipogenesis. METHODS: All rats were randomly divided into 3 groups: control group (C group), model group (M group), and intervention group (I group). The model of GC-ONFH was developed by a sequential administration of lipopolysaccharide and methylprednisolone. The rats in the I group were treated with caudal vein injection of hUC-MSCs. Six weeks later, the blood samples were obtained to measure the activity of alkaline phosphatase (ALP) and the content of triglyceride (TG) in serum, and the femoral heads were harvested and observed by hematoxylin-eosin staining, Micro-CT, Western blot and real-time quantitative polymerase chain reaction. RESULTS: After intervention of hUC-MSCs, the necrosis rate of femoral head decreased from 83% (10/12) to 33% (4/12), the rate of empty bone lacuna was significantly decreased, the activity of ALP increased significantly, the content of TG decreased significantly, the bone density increased obviously, the expression of RUNX2 and Col I increased significantly and the expression of PPARγ decreased significantly. CONCLUSION: These results revealed that caudal vein injection of hUC-MSCs can effectively reduce the incidence of GC-ONFH in rats by increasing ALP activity and reducing TG content in serum, increasing bone mineral density, promoting the expression of RUNX2 and Col I, and inhibiting the expression of PPARγ.

14.
Oral Oncol ; 122: 105555, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34619463

RESUMO

OBJECTIVE: We undertook this study to clarify how TPF, TP and PF induction chemotherapy (IC) regimens benefit for nasopharyngeal carcinoma (NPC) patients with different risk of disease progression. MATERIALS AND METHODS: Patients with newly diagnosed, stage III-IVA NPC were included. A quantitative nomogram was built using the independent prognostic factors identified for disease-free survival (DFS). Patients were stratified into low-risk and high-risk groups by the nomogram. Survival outcomes and toxicities between different IC regimens were compared. RESULTS: In total, 1647 (41.0%), 1123 (28.0%) and 1242 (31.0%) patients received TPF, PF and TP regimen, respectively. Consequently, 2253 (56.2%) patients were clarified as low-risk group and the other 1759 (43.8%) as high-risk group. Survival outcomes did not significantly differ between TPF, PF and TP regimens within the low-risk group. However, TPF was associated with significantly improved 3-year DFS (76.2% vs. 67.5% vs. 68.3%), overall survival (88.3% vs. 84.1% vs. 83.9%), distant metastasis-free survival (81.9% vs. 75.0% vs. 77.4%) and locoregional relapse-free survival (92.0% vs. 87.5% vs. 86.9%; all P < 0.05) compared with PF and TP within high-risk group. Multivariate analysis also confirmed these findings. Toxicity analysis showed that TP regimen has the highest percentage of grade 3-5 hematologic toxicities while PF regimen achieved the lowest percentages of overall grade 3-5 adverse events. CONCLUSIONS: Patients with high risk should receive TPF for better efficacy and PF may be a better choice for low-risk patients with regard to less grade 3-5 toxicities.

15.
ACS Nano ; 15(9): 15027-15038, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34469124

RESUMO

Lithium-sulfur (Li-S) batteries have attracted a great deal of attention for the next-generation energy storage devices due to their inherently high theoretical energy density, high natural abundance, and low cost. However, the dissolution of polysulfides in electrolytes and their undesirable shuttle behavior lead to poor cycling performance, which obstructs practical application. Herein, we report a dual-sulfur-fixing mechanism of epoxy/allyl compound/sulfur system to prepare poly(sulfur-random-4-vinyl-1,2-epoxycyclohexane) (SVE) copolymers as powerful cathode materials. Benefiting from the stable C-S bond and a uniform distribution of ultrafine Li2S/S8 in the SVE-based polymer matrix, the SVE electrodes exerted an embedding effect to reduce polysulfides migration. The thiosulfate/polythionate protective layer derived from the terminal hydroxyl group of SVE also ensured the cycle stability of SVE electrodes during cycling. As a result, optimized SVE electrodes deliver a high reversible specific capacity of 1248 mA h g-1 at rates of 0.1 C, together with a stable cycling performance of no capacity decay per cycle over more than 400 cycles. This work provides an effective strategy for the practical application of organosulfur polymers Li-S batteries and inspires the exploration of the reaction mechanism of epoxy/allyl compound/sulfur system.

16.
Front Plant Sci ; 12: 720593, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589100

RESUMO

Drought and salinity are the two major abiotic stresses constraining the crop yield worldwide. Both of them trigger cellular dehydration and cause osmotic stress which leads to cytosolic and vacuolar volume reduction. However, whether plants share a similar tolerance mechanism in response to these two stresses under natural conditions has seldom been comparatively reported. There are three different ecotypes of reed within a 5 km2 region in the Badanjilin desert of Northwest China. Taking the typical swamp reed (SR) as a control, we performed a comparative study on the adaption mechanisms of the two terrestrial ecotypes: dune reed (DR) and heavy salt meadow reed (HSMR) by physiological and proteomic approaches coupled with bioinformatic analysis. The results showed that HSMR and DR have evolved C4-like photosynthetic and anatomical characteristics, such as the increased bundle sheath cells (BSCs) and chloroplasts in BSCs, higher density of veins, and lower density and aperture of stomata. In addition, the thylakoid membrane fluidity also plays an important role in their higher drought and salinity tolerance capability. The proteomic results further demonstrated that HSMR and DR facilitated the regulation of proteins associated with photosynthesis and energy metabolism, lipid metabolism, transcription and translation, and stress responses to well-adapt to the drought and salinity conditions. Overall, our results demonstrated that HSMR and DR shaped a similar adaption strategy from the structural and physiological levels to the molecular scale to ensure functionality in a harsh environment.

17.
Transl Oncol ; 14(12): 101219, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34555726

RESUMO

BACKGROUND: It has been known for decades that circRNAs are deregulated in cancer. Here, we characterized the role and underlying mechanism of circ_0088212 in osteosarcoma. METHODS: The expression levels of circ_0088212, miR-520 h, and APOA1 were determined by RT-qPCR. RNase R digestion was performed to verify the circular structure of circ_0088212. CCK8 and transwell invasion assays were conducted to examine the in vitro malignancy of osteosarcoma. Caspase-3 activity was also measured. An in vivo model of osteosarcoma was constructed to examine the in vivo effect of circ_0088212 on osteosarcoma. Luciferase reporter, RNA RIP, and RNA pull-down assays were performed to verify the interaction between miR-520 h and APOA1 or circ_0088212. RESULTS: Circ_0088212 and APOA1 were expressed at low levels in osteosarcoma tissues and cells, while miR-520 h was highly expressed. Overexpression of circ_0088212 was found to inhibit the in vitro and in vivo growth of osteosarcoma. Mechanistically, miR-520 h was the target of circ_0088212 and APOA1 was the target of miR-520 h. Circ_0088212 downregulated miR-520 h expression, while miR-520 h overexpression abolished the inhibitory effect of circ_0088212 on osteosarcoma cell proliferation and migration. Furthermore, miR-520 h overexpression led to reduced APOA1 expression, while APOA1 overexpression counteracted the oncogenic effect of miR-520 h in osteosarcoma cells. CONCLUSION: Our findings demonstrated that circ_0088212 might exert a tumor-suppressive activity in osteosarcoma by sponging and sequestering miR-520 h away from APOA1. This suggests that the circ_0088212/miR-520 h/APOA1 axis may be a promising therapeutic target for osteosarcoma intervention.

18.
Front Mol Biosci ; 8: 727863, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532346

RESUMO

Eukaryotic Elongation Factor-2 Kinase (eEF2K) acts as a negative regulator of protein synthesis, translation, and cell growth. As a structurally unique member of the alpha-kinase family, eEF2K is essential to cell survival under stressful conditions, as it contributes to both cell viability and proliferation. Known as the modulator of the global rate of protein translation, eEF2K inhibits eEF2 (eukaryotic Elongation Factor 2) and decreases translation elongation when active. eEF2K is regulated by various mechanisms, including phosphorylation through residues and autophosphorylation. Specifically, this protein kinase is downregulated through the phosphorylation of multiple sites via mTOR signaling and upregulated via the AMPK pathway. eEF2K plays important roles in numerous biological systems, including neurology, cardiology, myology, and immunology. This review provides further insights into the current roles of eEF2K and its potential to be explored as a therapeutic target for drug development.

19.
MAGMA ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524564

RESUMO

OBJECTIVE: To propose a fully automated algorithm, which is implemented to segment subcutaneous adipose tissue (SAT) and internal adipose tissue (IAT) from the total adipose tissue for whole-body fat distribution analysis using proton density fat fraction (PDFF) magnetic resonance images. MATERIALS AND METHODS: Adipose tissue segmentation was implemented using the U-Net deep neural network model. All datasets were collected using a 3.0 T magnetic resonance imaging (MRI) scanner for whole-body scan of 20 volunteers covering from neck to knee with about 160 images for each volunteer. PDFF images were reconstructed based on chemical-shift-encoded fat-water imaging. After selecting the representative PDFF images (total 906 images), the manual labeling of the SAT area was used for model training (504 images), validation (168 images), and testing (234 images). RESULTS: The automatic segmentation model was validated through three indices using the validation and test sets. The dice similarity coefficient, precision rate, and recall rate were 0.976 ± 0.048, 0.978 ± 0.048, and 0.978 ± 0.050, respectively, in both validation and test sets. CONCLUSION: The proposed algorithm can reliably and automatically segment SAT and IAT from whole-body MRI PDFF images. The proposed method provides a simple and automatic tool for whole-body fat distribution analysis to explore the relationship between fat deposition and metabolic-related chronic diseases.

20.
Int J Med Robot ; : e2336, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586687

RESUMO

BACKGROUND: Oesophagogastric anastomosis is mainly complicated by its tediousness. We hope to modify an oesophagogastric anastomotic technique that simplifies anastomosis. METHODS: We conducted a retrospective analysis of 57 cases executed using reverse-puncture anastomotic (RPA) technique and 64 cases of manual purse anastomosis (MPA) technique for robot-assisted minimally invasive oesophagectomy (RAMIE). Baseline characteristics and perioperative outcomes were analysed. RESULTS: There were no significant differences between the 2 groups with regards to demographic data and clinical features. All patients had R0 resection. Relative to MPA, RPA group experienced significantly shorter operation times (232.5 ± 33.84 min vs. 262.3 ± 83.94 min, p = 0.038).RPA group patients had shorter anastomotic times relative to MPA group patients (10.5 ± 3.4 min vs. 18.3 ± 4.1 min, p = 0.014). No adverse events were observed. CONCLUSIONS: Reverse-puncture anastomosis is safe, feasible in RAMIE. This approach has the potential to efficiently shorten the anastomotic time and ensure safe operation.

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