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Introduction: The stability of a new hyperbaric ventilator (Shangrila590, Beijing Aeonmed Company, Beijing, China) at different clinically relevant pressures in a hyperbaric chamber during pressure-controlled ventilation (PCV) was investigated. Methods: The ventilator was connected to a test lung in the multiplace hyperbaric chamber. The inspiratory pressure (PI) of the ventilator was set to 1.0, 1.5, 2.0, 2.5 and 3.0 kPa (approximately 10, 15, 20, 25 and 30 cmH2O). The compliance and resistance of the test lung were set to 200 mL·kPa⁻¹ and 2 kPa·L⁻¹·s⁻¹, respectively. Experiments were conducted at 101, 203 and 284 kPa ambient pressure (1.0, 2.0 and 2.8 atmospheres absolute respectively). At each of the 5 PI values, the tidal volume (VT), peak inspiratory pressure (Ppeak) and peak inspiratory flow (Fpeak) displayed by the ventilator and the test lung were recorded for 20 cycles. Test lung data were considered the actual ventilation values. The ventilation data were compared among the three groups to evaluate the stability of the ventilator. Results: At every PI, the Ppeak detected by the ventilator decreased slightly with increasing ambient pressure. The Fpeak values measured by the test lung decreased substantially as the ambient pressure increased. Nevertheless, the reduction in VT at 284 kPa and PI 30 cmH2O (compared to performance at 101 kPa) was comparatively small (approximately 60 ml). Conclusions: In PCV mode this ventilator provided relatively stable VT across clinically relevant PI values to ambient pressures as high as 284 kPa. However, because Fpeak decreases at higher ambient pressure, some user adjustment might be necessary for precise VT maintenance during clinical use at higher PIs and ambient pressures.

Asunto(s)

Oxigenoterapia Hiperbárica , Volumen de Ventilación Pulmonar , Ventiladores Mecánicos , Oxigenoterapia Hiperbárica/métodos , Volumen de Ventilación Pulmonar/fisiología , Rendimiento Pulmonar/fisiología , Diseño de Equipo , Humanos , Cámaras de Exposición Atmosférica , Presión , Presiones Respiratorias Máximas , Presión Atmosférica , Respiración con Presión Positiva/métodos , Respiración con Presión Positiva/instrumentación , Respiración Artificial/instrumentación , Respiración Artificial/métodos

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Piezotronic effect utilizing strain-induced piezoelectric polarization to achieve interfacial engineering in semiconductor nanodevices exhibits great advantages in applications such as human-machine interfacing, micro/nanoelectromechanical systems, and next-generation sensors and transducers. However, it is a big challenge but highly desired to develop a highly sensitive piezotronic device based on piezoelectric semiconductor wafers and thus to push piezotronics toward wafer-scale applications. Here, we develop a bicrystal barrier-based piezotronic transistor for highly sensitive pressure sensing by p-GaN single-crystal wafers. Its pressure sensitivity can be as high as 19.83 meV/MPa, which is more than 15 times higher than previous bulk-material-based piezotronic transistors and reaches the level of nanomaterial-based piezotronic transistors. Moreover, it can respond to a very small strain of 3.3 × 10-6 to 1.1 × 10-5 with high gauge factors of 1.45 × 105 to 1.38 × 106, which is a very high value among various strain sensors. Additionally, it also exhibits high stability (current stability of 97.32 ± 2.05% and barrier height change stability of 95.85 ± 3.43%) and high linearity (R2 ∼ 0.997 ± 0.002) in pressure sensing. This work proves the possibility of designing a bicrystal barrier as the interface to obtain a strong piezotronic effect and highly sensitive piezotronic devices based on wafers, which contributes to their applications.

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Investigating interface engineering by piezoelectric, flexoelectric and ferroelectric polarizations in semiconductor devices is important for their applications in electronics, optoelectronics, catalysis and many more. The interface engineering by polarizations strongly depends on the property of interface barrier. However, the fixed value and uncontrollability of interface barrier once it is constructed limit the performance and application scenarios of interface engineering by polarizations. Here, we report a strategy of tuning piezotronic effect (interface barrier and transport controlled by piezoelectric polarization) reversibly and accurately by electric pulse. Our results show that for Ag/HfO2/n-ZnO piezotronic tunneling junction, the interface barrier height can be reversibly tuned as high as 168.11 meV by electric pulse, and the strain (0-1.34‰) modulated current range by piezotronic effect can be switched from 0-18 nA to 44-72 nA. Moreover, piezotronic modification on interface barrier tuned by electric pulse can be up to 148.81 meV under a strain of 1.34‰, which can totally switch the piezotronic performance of the electronics. This study provides opportunities to achieve reversible control of piezotronics, and extend them to a wider range of scenarios and be better suitable for micro/nano-electromechanical systems.

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OBJECTIVE: To delve deeply into the dynamic trajectories of cell subpopulations and the communication network among immune cell subgroups during the malignant progression of glioblastoma (GBM), and to endeavor to unearth key risk biomarkers in the GBM malignancy progression, so as to provide a more profound understanding for the treatment and prognosis of this disease by integrating transcriptomic data and clinical information of the GBM patients. METHODS: Utilizing single-cell sequencing data analysis, we constructed a cell subgroup atlas during the malignant progression of GBM. The Monocle2 tool was employed to build dynamic progression trajectories of the tumor cell subgroups in GBM. Through gene enrichment analysis, we explored the biological processes enriched in genes that significantly changed with the malignancy progression of GBM tumor cell subpopulations. CellChat was used to identify the communication network between the different immune cell subgroups. Survival analysis helped in identifying risk molecular markers that impacted the patient prognosis during the malignant progression of GBM. This method ological approach offered a comprehensive and detailed examination of the cellular and molecular dynamics within GBM, providing a robust framework for understanding the disease' s progression and potential therapeutic targets. RESULTS: The analysis of single-cell sequencing data identified 6 different cell types, including lymphocytes, pericytes, oligodendrocytes, macrophages, glioma cells, and microglia. The 27 151 cells in the single-cell dataset included 3 881 cells from the patients with low-grade glioma (LGG), 10 166 cells from the patients with newly diagnosed GBM, and 13 104 cells from the patients with recurrent glioma (rGBM). The pseudo-time analysis of the glioma cell subgroups indicated significant cellular heterogeneity during malignant progression. The cell interaction analysis of immune cell subgroups revealed the communication network among the different immune subgroups in GBM malignancy, identifying 22 biologically significant ligand-receptor pairs across 12 key biological pathways. Survival analysis had identified 8 genes related to the prognosis of the GBM patients, among which SERPINE1, COL6A1, SPP1, LTF, C1S, AEBP1, and SAA1L were high-risk genes in the GBM patients, and ABCC8 was low-risk genes in the GBM patients. These findings not only provided new theoretical bases for the treatment of GBM, but also offered fresh insights for the prognosis assessment and treatment decision-making for the GBM patients. CONCLUSION: This research comprehensively and profoundly reveals the dynamic changes in glioma cell subpopulations and the communication patterns among the immune cell subgroups during the malignant progression of GBM. These findings are of significant importance for understanding the complex biological processes of GBM, providing crucial new insights for precision medicine and treatment decisions in GBM. Through these studies, we hope to provide more effective treatment options and more accurate prognostic assessments for the patients with GBM.

Asunto(s)

Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patología , Neoplasias Encefálicas/genética , Recurrencia Local de Neoplasia , Pronóstico , Comunicación Celular , Carboxipeptidasas , Proteínas Represoras

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Mechanical sensors are mainly divided into two types (vertical force sensing and lateral strain sensing). Up to now, one sensor with two working modes is still a challenge. Here, we demonstrate a structural design concept combing a piezoelectric nano/microwire with a flexible polymer with protrusions that enables a dual-modal piezotronic transistor (DPT) with two working modes for highly sensitive vertical force sensing and lateral strain sensing. For vertical force sensing, DPT exhibits a force sensitivity up to 221.5 N-1 and a minimum identifiable force down to 21 mN, corresponding to a pressure sensitivity of 1.759 eV/MPa. For lateral strain sensing, DPT can respond to a large compression strain (~5.8%) with an on/off ratio up to 386.57 and a gauge factor up to 8988.6. It is a universal design that can integrate vertical force sensing and lateral strain sensing into only one nanodevice, providing a feasible strategy for multimodal devices.

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INTRODUCTION: The performance of the Shangrila590 hyperbaric ventilator (Beijing Aeonmed Company, Beijing, China) was evaluated during volume-controlled ventilation. METHODS: Experiments were conducted in a multiplace hyperbaric chamber at 101, 152, 203, and 284 kPa (1.0, 1.5, 2.0 and 2.8 atmospheres absolute [atm abs]). With the ventilator in volume control ventilation (VCV) mode and connected to a test lung, comparison was made of the set tidal volume (VTset) versus delivered tidal volume (VT) and minute volume (MV) at VTset between 400 and 1,000 mL. Peak inspiratory pressure was also recorded. All measurements were made across 20 respiratory cycles. RESULTS: Across all ambient pressures and ventilator settings the difference between VTset and actual VT and between predicted MV and actual MV were small and clinicially insignificant despite reaching statistical significance. Predictably, Ppeak increased at higher ambient pressures. With VTset 1,000 mL at 2.8 atm abs the ventilator produced significantly greater VT, MV and Ppeak. CONCLUSIONS: This new ventilator designed for use in hyperbaric environments performs well. It provides relatively stable VT and MV during VCV with VTset from 400 mL to 800 mL at ambient pressures from 1.0 to 2.8 atm abs, as well as VTset 1,000 mL at ambient pressures from 1.0 to 2.0 atm abs.

Asunto(s)

Oxigenoterapia Hiperbárica , Humanos , Ventiladores Mecánicos , Volumen de Ventilación Pulmonar , Pulmón , Oxígeno , Respiración Artificial

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Hyperbaric oxygen (HBO) therapy is an effective treatment for patients with disorders of consciousness (DOC). In this study, real-time electroencephalogram (EEG) recordings were obtained from patients with DOC during HBO therapy. EEG microstate indicators including mean microstate duration (MMD), ratio of total time covered (RTT), global explained variance (GEV), transition probability, mean occurrence, and mean global field power (GFP) were compared before and during HBO therapy. The results showed that the duration of microstate C in all patients with DOC increased after 20 min of HBO therapy (p < 0.05). Further statistical analysis found that the duration of microstate C was longer in the higher CRS-R group (≥8, 17 cases) than in the lower group (<8, 24 cases) during HBO treatment. In the higher CRS-R group, the transition probabilities from microstate A to microstate C and from microstate C to microstate A also increased significantly compared with the probability before treatment (p < 0.05). Microstate C is generally considered to be related to a salience network; an increase in the transition probability between microstate A and microstate C indicates increased information exchange between the auditory network and the salience network. The results of this study show that HBO therapy has a specific activating effect on attention and cognitive control in patients and causes increased activity in the primary sensory cortex (temporal lobe and occipital lobe). This study demonstrates that real-time EEG detection and analysis during HBO is a clinically feasible method for assessing brain function in patients with DOC. During HBO therapy, some EEG microstate indicators show significant changes related to the state of consciousness in patients with chronic DOC. This will be complementary to important electrophysiological indicators for assessing consciousness and may also provide an objective foundation for the precise treatment of patients with DOC.

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@#[摘 要] 目的：构建基于靶点人源化小鼠的程序性死亡受体-1（PD-1）/细胞毒性T淋巴细胞抗原-4（CTLA-4）双特异性抗体（BsAb）并对BsAb及其IgG1亚型进行抗癌活性评价和探讨其潜在的作用机制。方法：构建和扩增并纯化不同结构及抗体亚型的PD-1/CTLA-4抗体BsAb1、BsAb2和BsAb3，对纯化BsAb进行靶点亲和力检测，采用荧光素酶报告基因实验和FCM检测抗体的生物学活性。基于B-hPD-1-hPD-L1-hCTLA-4人源化小鼠的MC38-hPD-L1结肠癌细胞移植瘤模型对BsAb进行体内药效评估，并通过移植瘤组织中肿瘤浸润淋巴细胞（TIL）分析PD-1/CTLA-4抗体的作用机制。结果：成功制备的BsAb1、BsAb2及BsAb3对靶点PD-1和CTLA-4均有较强的特异性亲和力、对靶点通路均有不同程度的阻滞活性，均明显抑制移植瘤的生长（P<0.05或P<0.01）。IgG1亚型BsAb体内药效更优（P<0.01），TIL分析发现BsAb2-IgG1明显增加了CTL百分率（P<0.05），显著降低了肿瘤浸润Treg细胞百分率（P<0.01），使肿瘤免疫微环境更有利于杀伤肿瘤细胞；增强ADCC活性的Fc突变体亚型BsAb2-SI则不能进一步提高抗肿瘤活性。结论：具有Fc效应功能的IgG1亚型的PD-1/CTLA-4抗体体内抗癌药效更优，因其可以更好地清除TIL中的Treg细胞。

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Piezotronics with capacity of constructing adaptive and seamless interactions between electronics/machines and human/ambient are of value in Internet of Things, artificial intelligence and biomedical engineering. Here, we report a kind of highly sensitive strain sensor based on piezotronic tunneling junction (Ag/HfO2/n-ZnO), which utilizes the strain-induced piezoelectric potential to control the tunneling barrier height and width in parallel, and hence to synergistically modulate the electrical transport process. The piezotronic tunneling strain sensor has a high on/off ratio of 478.4 and high gauge factor of 4.8 × 105 at the strain of 0.10%, which is more than 17.8 times larger than that of a conventional Schottky-barrier based strain sensor in control group as well as some existing ZnO nanowire or nanobelt based sensors. This work provides in-depth understanding for the basic mechanism of piezotronic modulation on tunneling junction, and realizes the highly sensitive strain sensor of piezotronic tunneling junction on device scale, which has great potential in advanced micro/nano-electromechanical devices and systems.

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BACKGROUND: Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor with grim prognosis. Aberrant DNA methylation is an epigenetic mechanism that promotes GBM carcinogenesis, while the function of DNA methylation at enhancer regions in GBM remains poorly described. RESULTS: We integrated multi-omics data to identify differential methylation enhancer region (DMER)-genes and revealed global enhancer hypomethylation in GBM. In addition, a DMER-mediated target genes regulatory network and functional enrichment analysis of target genes that might be regulated by hypomethylation enhancer regions showed that aberrant enhancer regions could contribute to tumorigenesis and progression in GBM. Further, we identified 22 modules in which lncRNAs and mRNAs synergistically competed with each other. Finally, through the construction of drug-target association networks, our study identified potential small-molecule drugs for GBM treatment. CONCLUSIONS: Our study provides novel insights for understanding the regulation of aberrant enhancer region methylation and developing methylation-based biomarkers for the diagnosis and treatment of GBM.

Asunto(s)

Neoplasias Encefálicas , Glioblastoma , Biomarcadores de Tumor , Neoplasias Encefálicas/genética , Metilación de ADN , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Glioblastoma/genética , Humanos

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BACKGROUND: Increasing morbidity and misdiagnosis of vestibular migraine (VM) gravely affect the treatment of the disease as well as the patients' quality of life. A powerful diagnostic prediction model is of great importance for management of the disease in the clinical setting. MATERIALS AND METHODS: Patients with a main complaint of dizziness were invited to join this prospective study. The diagnosis of VM was made according to the International Classification of Headache Disorders. Study variables were collected from a rigorous questionnaire survey, clinical evaluation, and laboratory tests for the development of a novel predictive diagnosis model for VM. RESULTS: A total of 235 patients were included in this study: 73 were diagnosed with VM and 162 were diagnosed with non-VM vertigo. Compared with non-VM vertigo patients, serum magnesium levels in VM patients were lower. Following the logistic regression analysis of risk factors, a predictive model was developed based on 6 variables: age, sex, autonomic symptoms, hypertension, cognitive impairment, and serum Mg2+ concentration. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.856, which was better than some of the reported predictive models. CONCLUSION: With high sensitivity and specificity, the proposed logistic model has a very good predictive capability for the diagnosis of VM. It can be used as a screening tool as well as a complementary diagnostic tool for primary care providers and other clinicians who are non-experts of VM.

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The rate of hyperglycaemia in people around the world is increasing at an alarming rate at present, and innovative methods of alleviating hyperglycaemia are needed. The effects of Jerusalem artichoke inulin on hyperglycaemia, liver-related genes and the intestinal microbiota in mice fed a high-fat diet (HFD) and treated with streptozotocin (STZ) to induce hyperglycaemia were investigated. Inulin-treated hyperglycaemic mice had decreased average daily food consumption, body weight, average daily water consumption and relative liver weight and blood concentrations of TAG, total cholesterol, HDL-cholesterol and fasting blood glucose. Liver-related gene expressions in hyperglycaemic (HFD-fed and STZ-treated) compared with control mice showed eighty-four differentially expressed genes (forty-nine up-regulated and thirty-five down-regulated). In contrast, hyperglycaemic mice treated with inulin had twenty-two differentially expressed genes compared with control ones. Using Illumina high-throughput sequencing technology, the rarefaction and the rank abundance curves as well as the α diversity indices showed the treatment-induced differences in bacterial diversity in intestine. The linear discriminant analysis of effect size showed that the inulin treatment improved intestinal microbiota; in particular, it significantly increased the number of Bacteroides in the intestine of mice. In conclusion, inulin is potentially an effective functional food for the prevention and/or treatment of hyperglycaemia.

Asunto(s)

Diabetes Mellitus Experimental/terapia , Microbioma Gastrointestinal/efectos de los fármacos , Helianthus/química , Hiperglucemia/terapia , Inulina/farmacología , Tubérculos de la Planta/química , Animales , Diabetes Mellitus Experimental/etiología , Dieta Alta en Grasa/efectos adversos , Hiperglucemia/etiología , Ratones , Ratones Obesos

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Glioblastoma multiforme (GBM) is the most malignant brain tumor with a poor prognosis. A molecular level classification of GBM can provide insight into accurate patient-specific treatment. Competitive endogenous RNAs (ceRNAs), such as long non-coding RNAs (lncRNAs), play an essential role in the development of tumors and are associated with survival. However, the pattern of lncRNA-mediated ceRNA (LMce) crosstalk in different GBM subtypes is still unclear. In this study, we present a computational cascade to construct LMce networks of different GBM subtypes and investigate the lncRNA-mRNA regulations among them. Our results showed that although most lncRNAs and mRNAs in the different GBM subtype networks were the same, the regulation relationships of these RNAs were different among subtypes. 42.5%, 50.9%, 43.5% and 65.0% lncRNA-mRNA regulatory pairs were classic (CL)-, mesenchymal (MES)-, proneural (PN)- and neural (NE)-specific. In addition, our study identified 61, 132, 24 and 16 modules in which lncRNAs and mRNAs synergically competed with each other for miRNAs as CL-, MES-, PN- and NE-specific. CL- and MES-specific modules were mainly involved in biological functions such as cell proliferation, apoptosis and migration, while PN- and NE-specific modules were mainly related to DNA damage and cell cycle dysregulation. Survival analysis demonstrated that some modules could be potential prognostic markers of patients of CL and MES subtypes. This study uncovered the LMce interaction patterns in different GBM subtypes, identified subtype-specific modules with distinct biological functions, and revealed the potential prognostic markers of patients of different GBM subtypes. These results might contribute to the discovery of the GBM prognostic biomarkers and development of a more accurate therapeutic process.

Asunto(s)

Regulación Neoplásica de la Expresión Génica , Glioblastoma/diagnóstico , Glioblastoma/genética , MicroARNs/genética , Interferencia de ARN , ARN Largo no Codificante/genética , ARN Mensajero/genética , Biología Computacional/métodos , Curaduría de Datos , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos

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The low loading and poor cycling performance of sulfur cathodes are among the critical barriers restricting the practical application of lithium-sulfur (Li-S) batteries. The rational design of composites consisting of transition metals and conductive nanocarbon is considered an effective strategy to construct cathode materials for Li-S batteries with excellent cycling stability and rate capability. Herein, we propose a spray drying method to fabricate 3D pomegranate-like titanium nitride (TiN)@graphene composites as hosts for sulfur cathodes. The hollow spheres are coated with graphene layers to form a shell, serving as a highly efficient electrochemical reaction chamber and a reservoir for polysulfides. The TiN@graphene/S electrode exhibits an excellent capacity of 810 mA h g-1 after 200 cycles at 0.5C. The cathodes with high areal sulfur loadings of 2.8 and 3.6 mg cm-2 maintained remarkable capacities of 568 and 515 mA h g-1, respectively, after 500 cycles. The TiN hollow spheres not only accommodate the large volume expansion of sulfur but also improve the conversion of polysulfides during the discharge/charge process. The excellent electrical conductivity of the few-layered graphene shell facilitates electron transport and maintains structural stability. This work offers a strategy to combine inorganic compounds and nanocarbon as sulfur hosts to improve the electrochemical properties of Li-S batteries.

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We investigated the effects of tonsillectomy by low-temperature plasma on the growth development and psychological behavior in children with obstructive sleep apnea hypopnea syndrome (OSAHS).This study included 72 moderate and severe OSAHS children with tonsils or adenoids hypertrophy, which were randomly assigned into either the study group (n = 36) or the control group (n = 36). Patients in study group underwent tonsillectomy by low-temperature plasma, while in the control group underwent tonsil-pecking, then the efficacy were compared.The time of surgery, VAS scores on postoperative day 1, 3, and 7 were significantly lower in the study group than in the control group, and the efficiency was significantly higher in the study group than the control group (P = .018). In the study group, the BMI was lower, the score of C-WISC (VIQ, PIQ, and FIQ) was higher, the score of CBCL social competence was higher and the score of behavioral questions was lower than that in the control group; differences were statistically significant (P = .022). The serum levels of IgA, IgG, and IgM, as well as the percentage of T lymphocytes, between the study group and the control group were not significantly different (P = .132).Tonsillectomy by low-temperature plasma was effective on the treatment of children with severe OSAHS, and could improve growth development and psychological behavior.

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Coagulación con Plasma de Argón/métodos , Conducta Infantil/fisiología , Desarrollo Infantil , Apnea Obstructiva del Sueño , Tonsilectomía/métodos , Tonsila Faríngea/patología , Tonsila Faríngea/cirugía , Niño , Preescolar , Femenino , Humanos , Masculino , Tonsila Palatina/patología , Tonsila Palatina/cirugía , Polisomnografía/métodos , Periodo Posoperatorio , República de Corea , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/psicología , Resultado del Tratamiento

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Protein-mediated endocytosis of membrane is a key event in biological system. The mechanism, however, is still not clear. Using a de novo designed bola-type peptide KKKLLLLLLLLKKK (K3L8K3) as a protein mimic, we studied how it induced giant unilamellar vesicle (GUV) to form inward buds or endocytosis at varying conditions. Results show that the inward budding is initiated as the charged lipids are neutralized by K3L8K3, which results in a negative spontaneous curvature. If the charged lipids have unsaturated tails, the buddings are slim fibrils, which can further wrap into a spherical structure. In the case of saturated charged lipids, the buddings are rigid tubules, stable in the studied time period. The unsaturated lipid to saturated lipid ratio in the mother membrane is another key parameter governing the shape and dynamics of the buds. A complete endocytosis is observed when K3L8K3 is attached with a hydrophobic moiety, suggesting that hydrophobic interaction helps the buds to detach from the mother membrane. The molecules in the surrounding medium, such as negatively charged oligonucleotides, are engulfed into the GUV via endocytosis pathway induced by K3L8K3. Our study provides a novel strategy for illustrating the endocytosis mechanism by using peptides of simple sequence.

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Endocitosis/fisiología , Membranas/metabolismo , Péptidos/química , Interacciones Hidrofóbicas e Hidrofílicas , Lípidos/química , Imitación Molecular

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The behavior of nanocarriers, even though they are well-defined at equilibrium conditions, is unpredictable in living system. Using the complexes formed by plasmid DNA (pDNA) and K20 (K: lysine), protamine, or polylysine (PLL) as models, we studied the dynamic behavior of gene carriers in the presence of fetal bovine serum (FBS) and under different shear rates, a condition mimicking the internal physical environment of blood vessels. Without shear, all the positively charged complexes bind to the negatively charged proteins in FBS, leading to the formation of large aggregates and even precipitates. The behaviors are quite different under shear. The shear generates two effects: a mechanical force to break down the complex into smaller size particles above a critical shear rate and a stirring effect leading to secondary aggregation of complexes below the critical shear rate. In the studied shear rate from 100 to 3000 s-1, the mechanical force plays a key role in K20/pDNA and protamine/pDNA, while the stirring effect is dominant in PLL/pDNA. A model study shows that the interfacial tension, the chain density, and the elasticity of the complexes determine their responsiveness to shear force. This study is helpful to understand the fate of drug/gene carriers under physiological conditions. It also gains insight in designing drug/gene carriers with desirable properties for in vivo applications.

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ADN/química , Plásmidos/química , Suero/química , Estrés Mecánico , Animales , Bovinos , Protaminas/química

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BACKGROUND: Jumonji C domain 2A (JMJD2A), as a histone demethylases, plays a vital role in tumorigenesis and progression. But, its functions and underlying mechanisms of JMJD2A in nasopharyngeal carcinoma (NPC) metabolism are remained to be clarified. In this study, we investigated glycolysis regulation by JMJD2A in NPC and the possible mechanism. METHODS: JMJD2A expression was detected by Western blotting and Reverse transcription quantitative real-time PCR analysis. Then, we knocked down and ectopically expressed JMJD2A to detect changes in glycolytic enzymes. We also evaluated the impacts of JMJD2A-lactate dehydrogenase A (LDHA) signaling on NPC cell proliferation, migration and invasion. ChIP assays were used to test whether JMJD2A bound to the LDHA promoter. Finally, IHC was used to verify JMJD2A and LDHA expression in NPC tissue samples and analyze their correlation between expression and clinical features. RESULTS: JMJD2A was expressed at high levels in NPC tumor tissues and cell lines. Both JMJD2A and LDHA expression were positively correlated with the tumor stage, metastasis and clinical stage. Additionally, the level of JMJD2A was positively correlated with LDHA expression in NPC patients, and higher JMJD2A and LDHA expression predicted a worse prognosis. JMJD2A alteration did not influence most of glycolytic enzymes expression, with the exception of PFK-L, PGAM-1, LDHB and LDHA, and LDHA exhibited the greatest decrease in expression. JMJD2A silencing decreased LDHA expression and the intracellular ATP level and increased LDH activity, lactate production and glucose utilization, while JMJD2A overexpression produced the opposite results. Furthermore, JMJD2A could combine to LDHA promoter region and regulate LDHA expression at the level of transcription. Activated JMJD2A-LDHA signaling pathway promoted NPC cell proliferation, migration and invasion. CONCLUSIONS: JMJD2A regulated aerobic glycolysis by regulating LDHA expression. Therefore, the novel JMJD2A-LDHA signaling pathway could contribute to the Warburg effects in NPC progression.

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Carcinoma/genética , Carcinoma/metabolismo , Regulación Neoplásica de la Expresión Génica , Histona Demetilasas con Dominio de Jumonji/metabolismo , L-Lactato Deshidrogenasa/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Adenosina Trifosfato/metabolismo , Adulto , Anciano , Biomarcadores , Carcinoma/mortalidad , Carcinoma/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Progresión de la Enfermedad , Activación Enzimática , Femenino , Expresión Génica , Genes Reporteros , Glucosa/metabolismo , Glucólisis , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Estimación de Kaplan-Meier , L-Lactato Deshidrogenasa/metabolismo , Lactato Deshidrogenasa 5 , Ácido Láctico/metabolismo , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Clasificación del Tumor , Estadificación de Neoplasias , Transducción de Señal , Transcripción Genética

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Hierarchical mesoporous core-shell CoMn2O4@MnO2 nanoneedle arrays on nickel foam have been manufactured via a two-step hydrothermal process. Electrochemical performances of the CoMn2O4@MnO2 nanomaterials have been tested for supercapacitors and demonstrated outstanding properties. The CoMn2O4@MnO2 electrode delivers a specific capacitance of 2126 F g-1 at a current density of 1 A g-1 in 2 M KOH aqueous solution and also shows an excellent cycling stability, which retains 94.4% of the initial capacitance after 5000 charge/discharge cycles at a current density of 4 A g-1. The result confirms the superiority of the CoMn2O4@MnO2 electrode compared with the CoMn2O4 electrode and demonstrates the potential application of the CoMn2O4@MnO2 nanoneedle array electrode for high-performance energy storage device applications.

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Hyperbaric oxygen (HBO) therapy through breathing oxygen at the pressure of above 1 atmosphere absolute (ATA) is useful for varieties of clinical conditions, especially hypoxic-ischemic diseases. Because of generation of reactive oxygen species (ROS), breathing oxygen gas at high pressures can cause oxygen toxicity in the central nervous system, leading to multiple neurological dysfunction, which limits the use of HBO therapy. Studies have shown that Hydrogen gas (H2) can diminish oxidative stress and effectively reduce active ROS associated with diseases. However, the effect of H2 on ROS generated from HBO therapy remains unclear. In this study, we investigated the effect of H2 on ROS during HBO therapy using PC12 cells. PC12 cells cultured in medium were exposed to oxygen gas or mixed oxygen gas and H2 at 1 ATA or 5 ATA. Cells viability and oxidation products and ROS were determined. The data showed that H2 promoted the cell viability and inhibited the damage in the cell and mitochondria membrane, reduced the levels of lipid peroxidation and DNA oxidation, and selectively decreased the levels of •OH but not disturbing the levels of O2•-, H2O2, or NO• in PC12 cells during HBO therapy. These results indicated that H2 effectively reduced •OH, protected cells against oxygen toxicity resulting from HBO therapy, and had no effect on other ROS. Our data supported that H2 could be potentially used as an antioxidant during HBO therapy.

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Hidrógeno/farmacología , Radical Hidroxilo/metabolismo , Oxígeno/toxicidad , Animales , Supervivencia Celular/efectos de los fármacos , L-Lactato Deshidrogenasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismo