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1.
Molecules ; 28(18)2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37764485

RESUMEN

The elucidation of the molecular driving forces responsible for Liquid-liquid Phase Separation (LLPS) of proteins and nucleic acids within living cells is crucial for understanding its biological functions and its role in related diseases. In the present study, we investigated the regulation of LLPS in a series of polypeptides with repetitive proline and arginine (PR) sequences by modifying their length and the salt concentration in the solution. Our findings indicate that higher salt concentrations are necessary for LLPS of repetitive PR peptides longer than eight PRs, which emerges as a threshold value. To pinpoint the molecular forces driving the LLPS in peptides, we sequentially introduced various concentrations of hydrophobic disruptors, such as 1,6-hexanediol, and electrostatic regulators, such as ethyl alcohol and 6-Aminocaproic acid. We further modulated the electrostatic interaction by introducing ethyl alcohol and 6-Aminocaproic acid to alter the dielectric constant of the solution. The inclusion of ethyl alcohol intensified the electrostatic interaction between arginine molecules, facilitating LLPS of PR15, while 6-Aminocaproic acid yielded the reverse effect. We deduced that the phase separation in peptide systems is conjointly driven by hydrophobicity and electrostatic interactions. These insights can guide the regulation of LLPS in other peptide and protein systems, and could be pivotal in addressing abnormal aggregations of proteins and nucleic acids.


Asunto(s)
Ácido Aminocaproico , Ácidos Nucleicos , Péptidos , Cloruro de Sodio , Arginina , Etanol , Cloruro de Sodio Dietético
2.
Int J Mol Sci ; 23(8)2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-35457204

RESUMEN

DNA damage is closely related to cancer and many aging-related diseases. Peroxynitrite is a strong oxidant, thus a typical DNA damage agent, and is a major mediator of the inflammation-associated pathogenesis. For the first time, we directly visualized the process of DNA damage by peroxynitrite and DNA protection by ectoine via atomic force microscopy in liquid. We found that the persistence length of DNA decreases significantly by adding a small amount of peroxynitrite, but the observed DNA chains are still intact. Specifically, the persistence length of linear DNA in a low concentration of peroxynitrite (0 µM to 200 µM) solution decreases from about 47 nm to 4 nm. For circular plasmid DNA, we observed the enhanced superhelices of plasmid DNA due to the chain soften. When the concentration of peroxynitrite was above 300 µM, we observed the fragments of DNA. Interestingly, we also identified single-stranded DNAs during the damage process, which is also confirmed by ultraviolet spectroscopy. However, if we added 500 mM ectoine to the high concentration PN solution, almost no DNA fragments due to double strand breaks were observed because of the protection of ectoine. This protection is consistent with the similar effect for DNA damage caused by ionizing radiation and oxygenation. We ascribe DNA protection to the preferential hydration of ectoine.


Asunto(s)
Daño del ADN , Ácido Peroxinitroso , ADN/química , Microscopía de Fuerza Atómica/métodos , Plásmidos/genética
3.
Int J Mol Sci ; 18(7)2017 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-28754018

RESUMEN

p53 is a tumor suppressor protein that plays a significant role in apoptosis and senescence, preserving genomic stability, and preventing oncogene expression. Metal ions, such as magnesium and zinc ions, have important influences on p53-DNA interactions for stabilizing the structure of the protein and enhancing its affinity to DNA. In the present study, we systematically investigated the interaction of full length human protein p53 with DNA in metal ion solution by atomic force microscopy (AFM). The p53-DNA complexes at various p53 concentrations were scanned by AFM and their images are used to measure the dissociation constant of p53-DNA binding by a statistical method. We found that the dissociation constant of p53 binding DNA is 328.02 nmol/L in physiological buffer conditions. The influence of magnesium ions on p53-DNA binding was studied by AFM at various ion strengths through visualization. We found that magnesium ions significantly stimulate the binding of the protein to DNA in a sequence-independent manner, different from that stimulated by zinc. Furthermore, the high concentrations of magnesium ions can promote p53 aggregation and even lead to the formation of self-assembly networks of DNA and p53 proteins. We propose an aggregation and self-assembly model based on the present observation and discuss its biological meaning.


Asunto(s)
ADN/metabolismo , Magnesio/farmacología , Proteína p53 Supresora de Tumor/química , Proteína p53 Supresora de Tumor/metabolismo , Secuencia de Bases , Sitios de Unión/efectos de los fármacos , Humanos , Microscopía de Fuerza Atómica , Modelos Moleculares , Agregado de Proteínas , Unión Proteica/efectos de los fármacos , Proteína p53 Supresora de Tumor/efectos de los fármacos
4.
Soft Matter ; 12(31): 6669-74, 2016 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-27427090

RESUMEN

Charge inversion and condensation of DNA in solutions of trivalent and quadrivalent counterions are significantly influenced by the pH value of the solution. We systematically investigated the condensation and charge compensation of DNA by spermidine, hexammine cobalt(iii) (cohex, [Co(NH3)6](3+)) and spermine in solutions of a wide range of pH values from 3 to 9.3 by dynamic light scattering, magnetic tweezers, and atomic force microscopy. In trivalent counterion solution, we found that there is a critical concentration (0.75 mM for cohex and 0.5 mM for spermidine), under which the electrophoresis mobility of DNA initially increases, reaches a maximum, and finally decreases when the pH value is decreased. In contrast, above the critical concentration, the electrophoretic mobility of DNA increases monotonously with decreasing pH value of the solution. The corresponding condensing force has the same dependence on the pH value. However, for the case of quadrivalent counterions, the electrophoretic mobility of DNA is monotonously promoted by lowering the pH value of the solution at any concentration of counterions in which charge inversion of DNA may occur. In atomic force microscopy images and force spectroscopy of magnetic tweezers, we found that maximal charge neutralization and condensation force correspond to the most compact DNA condensation. We propose a mechanism of promoting DNA charge neutralization: small and highly mobile hydrogen ions tend to attach to the DNA-counterion complex to further neutralize its remaining charge, which is related to the surface area of the complex. Therefore, this further neutralization is prominent when the complex is toroidal which corresponds to the case of mild ion concentration while it is less prominent for more compact globules or rod complexes at high counterion concentration.


Asunto(s)
ADN/química , Concentración de Iones de Hidrógeno , Cobalto , Electroforesis , Espermidina , Espermina
5.
Soft Matter ; 11(20): 4099-105, 2015 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-25913809

RESUMEN

In the preset study, we report the suppression and promotion of DNA charge inversion by mixing a quadrivalent counterion (spermine) with mono-, di- and trivalent counterions by dynamic light scattering (DLS) and single molecule electrophoresis (SME) methods. We find that the electrophoretic mobility of DNA in spermine solution decreases in the presence of monovalent sodium ions and divalent magnesium ions. It means that the charge neutralization of DNA by the quadrivalent counterion is suppressed when adding extra mono- or divalent counterions. More specifically, at a high concentration of spermine, the positive mobility can switch back to a negative value by adding mono- and divalent counterions. Thus, charge neutralization and inversion of DNA by quadrivalent counterions is suppressed in the mono- and divalent ion solution. However, the scenario changes dramatically when we add trivalent ions into the solution of DNA and spermine. In this case, the charge neutralization and inversion of DNA is promoted rather than suppressed by mixing with trivalent ions. The negative electrophoretic mobility can be promoted to a positive value, which corresponds to the charge inversion, by trivalent counterions. Thus trivalent and quadrivalent counterions work cooperatively in DNA charge neutralization and inversion. This promotion also occurs when highly positively charged chitosan is introduced into the solution. We explain the observation by the counterion complexation that is related to DNA condensation, which is supported by the images of atomic force microscopy (AFM).


Asunto(s)
ADN/química , Dispersión Dinámica de Luz , Electroforesis , Microscopía de Fuerza Atómica , Transición de Fase , Espermina/química
6.
Sci Rep ; 14(1): 13382, 2024 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862770

RESUMEN

Understanding the intricate interactions governing protein and peptide behavior in liquid-liquid phase separation (LLPS) is crucial for unraveling biological functions and dysfunctions. This study employs a residue-leveled coarse-grained molecular dynamics approach to simulate the phase separation of repetitive polyproline and polyarginine peptides (poly PR) with varying lengths and sequences in solution, considering different concentrations and temperatures. Our findings highlight the crucial role of sequence order in promoting LLPS in peptides with identical lengths of repetitive sequences. Interestingly, repetitive peptides containing fewer than 10 polyarginine repeats exhibit no LLPS, even at salt concentrations up to 3 M. Notably, our simulations align with experimental observations, pinpointing a salt concentration of 2.7 M for PR25-induced LLPS. Utilizing the same methodology, we predict the required salt concentrations for LLPS induction as 1.2 M, 1.5 M, and 2.7 M for PR12, PR15, and PR35, respectively. These predictions demonstrate good agreement with experimental results. Extending our investigation to include the peptide glutamine and arginine (GR15) in DNA solution, our simulations mirror experimental observations of phase separation. To unveil the molecular forces steering peptide phase separation, we introduce a dielectric constant modifier and hydrophobicity disruptor into poly PR systems. Our coarse-grained analysis includes an examination of temperature effects, leading to the inference that both hydrophobic and electrostatic interactions drive phase separation in peptide systems.


Asunto(s)
Simulación de Dinámica Molecular , Péptidos , Péptidos/química , Interacciones Hidrofóbicas e Hidrofílicas , Temperatura , Transición de Fase , ADN/química , ADN/metabolismo , Separación de Fases
7.
Bioact Mater ; 39: 14-24, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38783926

RESUMEN

Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented angiogenesis-immunosuppressive tumor microenvironment (TME). Herein, elevated neutrophil extracellular traps (NETs) and cancer-associated neurotransmitters (CANTs, e.g., catecholamines) are firstly identified as two of the dominant inducements. Further, an injectable fibrin-alginate hydrogel with high tissue adhesion has been constructed to specifically co-deliver NETs inhibitor (DNase I)-encapsulated PLGA nanoparticles and an unselective ß-adrenergic receptor blocker (propranolol). The two components (i.e., fibrin and alginate) can respond to two triggers (thrombin and Ca2+, respectively) in postoperative bleeding to gelate, shaping into an interpenetrating network (IPN) featuring high strength. The continuous release of DNase I and PR can wreck NETs and antagonize catecholamines to decrease microvessel density, blockade myeloid-derived suppressor cells, secrete various proinflammatory cytokines, potentiate natural killer cell function and hamper cytotoxic T cell exhaustion. The reprogrammed TME significantly suppress locally residual and distant tumors, induce strong immune memory effects and thus inhibit lung metastasis. Thus, targetedly degrading NETs and blocking CANTs enabled by this in-situ IPN-based hydrogel drug depot provides a simple and efficient approach against SR-induced cancer recurrence and metastasis.

8.
Adv Mater ; 36(11): e2307796, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38096869

RESUMEN

Benign prostatic hyperplasia (BPH) as the leading cause of urination disorder is still a refractory disease, and there have no satisfied drugs or treatment protocols yet. With identifying excessive Zn2+ , inflammation, and oxidative stress as the etiology of aberrant hyperplasia, an injectable sodium alginate (SA) and glycyrrhizic acid (GA)-interconnected hydrogels (SAGA) featuring Zn2+ -triggered in situ gelation are developed to load lonidamine for reprogramming prostate microenvironment and treating BPH. Herein, SAGA hydrogels can crosslink with Zn2+ in BPH via coordination chelation and switch free Zn2+ to bound ones, consequently alleviating Zn2+ -arisen inflammation and glycolysis. Beyond capturing Zn2+ , GA with intrinsic immunoregulatory property can also alleviate local inflammation and scavenge reactive oxygen species (ROS). Intriguingly, Zn2+ chelation-bridged interconnection in SAGA enhances its mechanical property and regulates the degradation rate to enable continuous lonidamine release, favoring hyperplastic acini apoptosis and further inhibiting glycolysis. These multiple actions cooperatively reprogram BPH microenvironment to alleviate characteristic symptoms of BPH and shrink prostate. RNA sequencing reveals that chemotaxis, glycolysis, and tumor necrosis factor (TNF) inflammation-related pathways associated with M1-like phenotype polarization are discerned as the action rationales of such endogenous Zn2+ -triggered in situ hydrogels, providing a candidate avenue to treat BPH.


Asunto(s)
Próstata , Hiperplasia Prostática , Humanos , Masculino , Próstata/metabolismo , Próstata/patología , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Hiperplasia/complicaciones , Hiperplasia/metabolismo , Hiperplasia/patología , Zinc , Inflamación/metabolismo , Hidrogeles/metabolismo
9.
J Phys Chem B ; 127(21): 4783-4789, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37205854

RESUMEN

The denaturation of DNA is a critical process in biology and has many biotechnological applications. We investigated the compaction of locally denatured DNA by a chemical denaturation agent, dimethyl sulfoxide (DMSO), using magnetic tweezers (MTs), atomic force microscopy (AFM), and dynamic light scattering (DLS). Our results show that DMSO not only is capable of denaturing DNA but also able to compact DNA directly. When the DMSO concentration is above 10%, DNA condensation occurs due to the reduction in the persistence length of DNA and excluded volume interactions. Meanwhile, locally denatured DNA is easily condensed by divalent cations, such as magnesium ions (Mg2+), contrasting with no native DNA condensation by the classical divalent cations. Specifically, the addition of more than 3 mM Mg2+ to a 5% DMSO solution leads to DNA condensation. The critical condensing force (FC) increases from 6.4 to 9.5 pN when the Mg2+ concentration grows from 3 to 10 mM. However, FC decreases gradually with a further increase in Mg2+ concentration. For 3% DMSO solution, above 30 mM Mg2+ is needed to compact DNA and a weaker condensing force was measured. With increasing Mg2+ concentration, the morphology of the DMSO partially denatured DNA complex changes from loosely random coils to a dense network structure, even forming a spherical condensation nucleus, and finally to a partially disintegrated network. These findings show that the elasticity of DNA plays an important role in its denaturation and condensation behavior.


Asunto(s)
ADN , Dimetilsulfóxido , Cationes Bivalentes , ADN/química , Núcleo Celular , Elasticidad , Cationes
10.
Ultrason Sonochem ; 98: 106480, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37393855

RESUMEN

Fuel droplet evaporation is essential to the generation of flammable mixtures in thermal engines. Generally, liquid fuel is injected directly into the hot, high-pressure atmosphere to form scattered droplets. Many investigations on droplet evaporation have been conducted with techniques involving the influence of boundaries, such as suspended wires. Ultrasonic levitation is a non-contact and non-destructive technology that can avoid the impact of hanging wire on droplet shape and heat transfer. Besides, it can simultaneously levitate multiple droplets and allow them to associate with each other or be used to study droplet instability behaviors. This paper reviews the influences of the acoustic field on levitated droplets, the evaporation characteristics of acoustically levitated droplets, and the prospects and limitations of ultrasonic suspension methods for droplet evaporation, which can serve as references for relevant studies.

11.
Am J Cancer Res ; 13(6): 2617-2629, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37424814

RESUMEN

This study utilized The Cancer Genome Atlas (TCGA) database to identify cuproptosis-related long non-coding RNAs (CRlncRNAs) in patients with kidney renal clear cell carcinoma (KIRC) which was further applied to construct risk signatures. All KIRC patients were divided into the training and the validation sets at a ratio of 7:3. Lasso regression analysis identified two prognosis-associated CRlncRNAs (LINC01204 and LINC01711), and prognostic risk signatures were constructed in both the training and the validation sets. Kaplan-Meier survival curves showed that patients with high-risk scores had significantly shorter overall survival (OS) than those with low-risk scores both in both the training and the validation sets. The area under the curve (AUC) of the prognostic nomogram generated based on age, grade, stage and risk signature to predict the 1-, 3- and 5-year OS were 0.84, 0.81 and 0.77, respectively, and the calibration curves also showed the high accuracy of the nomogram. In addition, we constructed the LINC01204/LINC01711-miRNA-mRNA ceRNA network graph. Finally, we experimentally investigated the function of LINC01711 by knocking down LINC01711 and revealed that knockdown of LINC01711 inhibited the proliferation, migration and invasion of KIRC cells. Hence, in this study, we developed a signature of prognostic risk-associated CRlncRNAs that could accurately predict the prognosis of KIRC patients and constructed a related ceRNA network to shed light on the mechanistic study of KIRC. LINC01711 might serve as a potential biomarker for the early diagnosis and prognosis of KIRC patients.

12.
Environ Sci Pollut Res Int ; 30(10): 26357-26366, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36367648

RESUMEN

Exposure to ethylene oxide may cause a number of diseases. The purpose of this study was to investigate whether there is an association between hemoglobin ethylene oxide (HbEO) and the risk of developing kidney stones in US adults. We analyzed 3348 patients from the National Health and Nutrition Survey (NHANES) 2013-2016 and conducted a cross-sectional study. Dose-response analysis curves of restricted cubic spline function, multiple logistic regression, and subgroup analysis were used to investigate the association between HbEO and the risk of kidney stones. Logistic regression models were used to analyze the correlation between HbEO and kidney stones. Among the 3348 participants, 3016 people self-reported having a kidney stone. After adjusting for age, sex, race, marital status, education level, diabetes, vigorous recreational activity, moderate recreational activity, body mass index, blood urea nitrogen, creatinine, eGFR, and uric acid, we found a positive association between HbEO and the risk of kidney stones. We divided patients into four groups based on quartiles of HbEO levels and performed multifactorial logistic regression after adjusting for confounders, which showed that the incidence of kidney stones increased with increasing HbEO concentrations compared with Q1 (Q2, OR = 0.922, 95% CI, 0. 657-1.295, P = 0.639; Q3, OR = 1.004, 95% CI, 0.713-1.414, P = 0.983; Q4, OR = 1.535, 95% CI, 1.114-2.114, P = 0.009). High levels of HbEO were positively correlated with the risk of kidney stone development and could be used as an indicator of kidney stone prevention.


Asunto(s)
Óxido de Etileno , Cálculos Renales , Humanos , Adulto , Encuestas Nutricionales , Prevalencia , Estudios Transversales , Cálculos Renales/epidemiología , Hemoglobinas
13.
Polymers (Basel) ; 14(7)2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35406251

RESUMEN

The interaction between DNA and proteins is fundamentally important not only for basic research in biology, but also for potential applications in nanotechnology. In the present study, the complexes formed by λ DNA and lysozyme in a dilute aqueous solution have been investigated using magnetic tweezers (MT), dynamic light scattering (DLS), and atomic force microscopy (AFM). We found that lysozyme induced DNA charge inversion by measuring its electrophoretic mobility by DLS. Lysozyme is very effective at neutralizing the positive charge of DNA, and its critical charge ration to induce charge inversion in solution is only 2.26. We infer that the high efficiency of charge neutralization is due to the highly positively charged (+8 e) and compact structure of lysozyme. When increasing the concentration of lysozymes from 6 ng·µL-1 to 70 ng·µL-1, DNA mobility (at fixed concentration of 2 ng·µL-1) increases from -2.8 to 1.5 (in unit of 10-4 cm2·V-1·S), implying that the effective charge of DNA switches its sign from negative to positive in the process. The corresponding condensing force increased from 0 pN to its maximal value of about 10.7 pN at concentrations of lysozyme at 25 ng·µL-1, then decreases gradually to 3.8 pN at 200 ng·µL-1. The maximal condensing force occurs at the complete DNA charge neutralization point. The corresponding morphology of DNA-lysozyme complex changes from loosely extensible chains to compact globule, and finally to less compact flower-like structure due to the change of attached lysozyme particles as observed by AFM.

14.
Biomolecules ; 13(1)2022 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-36671427

RESUMEN

Liquid-liquid phase separation (LLPS) underlies the formation of membrane-free organelles in eukaryotic cells and plays an important role in the development of some diseases. The phase boundary of metastable liquid-liquid phase separation as well as the cloud point temperature of some globular proteins characterize the phase behavior of proteins and have been widely studied theoretically and experimentally. In the present study, we used a regression and classification neural network to deal with the phase behavior of lysozyme and bovine serum albumin (BSA). We predicted the cloud point temperature and solubility of a lysozyme solution containing sodium chloride by regression and the reentrant phase behavior of BSA in YCl3 solution containing a surfactant dodecyl dimethyl amine oxide (DDAO) by classification. Specifically, our network model is capable of predicting (a) the solubility of lysozyme in the range: pH 4.0-5.4, temperature 0-25 °C, and NaCl concentration 2-7% (w/v); (b) the cloud point temperature of lysozyme in the range: pH 4.0-4.8, NaCl concentration 2-7%, and lysozyme concentration 0-400 mg/mL; and (c) the phase behavior of BSA in the range: DDAO 1-60 mM, BSA 30-100 mg/mL, and YCl3 1-20 mM. We experimentally tested the model at some prediction points with a high accuracy, which means that deep neural networks can be applicable in qualitative and quantitive analysis of liquid-liquid phase separation.


Asunto(s)
Muramidasa , Cloruro de Sodio , Cloruro de Sodio/química , Muramidasa/química , Albúmina Sérica Bovina/química , Cloruro de Sodio Dietético , Redes Neurales de la Computación
15.
RSC Adv ; 12(36): 23356-23365, 2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-36090395

RESUMEN

DNA denaturation is related to many important biological phenomena, such as its replication, transcription and the interaction with some specific proteins for single-stranded DNA. Dimethyl sulfoxide (DMSO) is a common chemical agent for DNA denaturation. In the present study, we investigate quantitatively the effects of different concentrations of DMSO on plasmid and linear DNA denaturation by atomic force microscopy (AFM) and UV spectrophotometry. We found that persistent length of DNA decreases significantly by adding a small amount of DMSO before ensemble DNA denaturation occurs; the persistence length of DNA in 3% DMSO solution decreases to 12 nm from about 50 nm without DMSO in solution. And local DNA denaturation occurs even at very low DMSO concentration (such as 0.1%), which can be directly observed in AFM imaging. Meanwhile, we observed the forming process of DNA contacts between different parts for plasmid DNA with increasing DMSO concentration. We suggest the initial mechanism of DNA denaturation as follows: DNA becomes more flexible due to the partial hydrogen bond braking in the presence of DMSO before local separation of the two complementary nucleotide chains.

16.
Nanoscale ; 14(36): 12984-12998, 2022 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-36056710

RESUMEN

Multidrug resistance (MDR) is one of the main reasons for the failure of tumor chemotherapy and has a negative influence on the therapeutic effect. MDR is primarily attributable to two mechanisms: the activation of efflux pumps for drugs, which can transport intracellular drug molecules from cells, and other mechanisms not related to efflux pumps, e.g., apoptosis prevention, strengthened DNA repair, and strong oxidation resistance. Nanodrug-delivery systems have recently attracted much attention, showing some unparalleled advantages such as drug targeting and reduced drug efflux, drug toxicity and side effects in reversing MDR. Notably, in drug-delivery platforms based on nanotechnology, multiple therapeutic strategies are integrated into one system, which can compensate for the limitations of individual strategies. In this review, the mechanisms of tumor MDR as well as common vectors and nanocarrier-combined therapy strategies to reverse MDR were summarized to promote the understanding of the latest progress in improving the efficiency of chemotherapy and synergistic strategies. In particular, the adoption of nanotechnology has been highlighted and the principles underlying this phenomenon have been elucidated, which may provide guidance for the development of more effective anticancer strategies.


Asunto(s)
Antineoplásicos , Neoplasias , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Humanos , Nanotecnología , Neoplasias/patología , Preparaciones Farmacéuticas
17.
Front Surg ; 9: 911411, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36248373

RESUMEN

Background: We evaluated the prognostic value of preoperative blood glucose to lymphocyte ratio (GLR) in renal cell carcinoma (RCC) patients who underwent laparoscopic nephrectomy through a multi-institutional clinical study. Methods: A total of 420 patients with RCC from three medical centers from 2014 to 2019 were included in this study. The effect of GLR on overall survival (OS) and cancer-specific survival (CSS) in RCC patients was assessed by Kaplan-Meier survival curves, univariate and multivariate Cox regression analysis. Moreover, a 1:1 propensity score matching (PSM) analysis of different GLR groups was utilized to further confirm the prognostic ability of GLR. Results: The optimal cut-off value for GLR was 6.8. Patients were divided into high GLR and low GLR groups according to the optimal cut-off value. GLR was significant association with diabetes, cardiovascular disease and AJCC stage. High GLR predicted adverse OS ( P = 0.002) and CSS ( P < 0.01) in RCC patients. Multivariate Cox regression analysis revealed that high GLR was an independent prognostic factor for OS [hazard ratio (HR): 2.389, 95% confidence interval (CI), 1.136-5.027, P = 0.008] and CSS (HR: 3.474, 95% CI, 1.555-7.761, P = 0.002). After PSM analysis of the patients in the high GLR and low GLR groups, high GLR still predicted poor OS ( P = 0.021) and CSS ( P = 0.037). Conclusions: High GLR is associated with adverse prognosis in RCC patients, and GLR can serve as an independent prognostic marker for OS and CSS in RCC patients receiving laparoscopic nephrectomy.

18.
RSC Adv ; 11(25): 15099-15105, 2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-35424055

RESUMEN

The understanding of DNA-surfactant interactions is important for fundamental physical biology and developing biomedical applications. In the present study, we demonstrated a DNA-surfactant nano-machine model by modulating the compaction of DNA in dodecyldimethylamine oxide (DDAO) solutions. By controlling DDAO concentration and pH of solution, we are able to adjust the compacting force of DNA so as to pull biomolecular subunits connected to it. The pulling force of the machine depends on DDAO concentration and pH of solution, ranging from near zero to about 4.6 pN for 10 mM DDAO concentration at pH = 4. The response time of the machine is about 3 minutes for contracting and 2 minutes for releasing in 5 mM DDAO solution. We found that DDAO has no significant influence on DNA under basic conditions, but compacts DNA under acidic conditions, which is enhanced with decreasing pH of solution. Meanwhile, we found the accompanying charge inversion of DNA in the process of DNA compaction by DDAO.

19.
PLoS One ; 16(9): e0256892, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34529699

RESUMEN

In Location-Based Social Networks (LBSNs), registered users submit their reviews for visited point-of-interests (POIs) to the system providers (SPs). The SPs anonymously publish submitted reviews to build reputations for POIs. Unfortunately, the user profile and trajectory contained in reviews can be easily obtained by adversaries who SPs has compromised with. Even worse, existing techniques, such as cryptography and generalization, etc., are infeasible due to the necessity of public publication of reviews and the facticity of reviews. Inspired by pseudonym techniques, we propose an approach to exchanging reviews before users submit reviews to SPs. In our approach, we introduce two attacks, namely review-based location correlation attack (RLCA) and semantic-based long-term statistical attack (SLSA). RLCA can be exploited to link the real user by reconstructing the trajectory, and SLSA can be launched to establish a connection between locations and users through the difference of semantic frequency. To resist RLCA, we design a method named User Selection to Resist RLCA (USR-RLCA) to exchange reviews. We propose a metric to measure the correlation between a user and a trajectory. Based on the metric, USR-RLCA can select reviews resisting RLCA to exchange by suppressing the number of locations on each reconstructed trajectory below the correlation. However, USR-RLCA fails to resist SLSA because of ignoring the essential semantics. Hence, we design an enhanced USR-RLCA named User Selection to Resist SLSA (USR-SLSA). We first propose a metric to measure the indistinguishability of locations concerning the difference of semantic frequency in a long term. Then, USR-SLSA can select reviews resisting SLSA to exchange by allowing two reviews whose indistinguishability is below the probability difference after the exchange to be exchanged. Evaluation results verify the effectiveness of our approach in terms of privacy and utility.


Asunto(s)
Algoritmos , Seguridad Computacional , Privacidad , Red Social , Humanos
20.
J Chem Phys ; 130(17): 174706, 2009 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-19425797

RESUMEN

The quantum dynamics of the photodetached electron of H(-) in electric field near a surface are studied in the time domain. The evolution of wave packet for different manifold eigenstates with limited lifetimes is obtain analytically. It is found that the quantum coherence and temporal evolution of surface electronic wave packet can be controlled by the laser central energy and electric field. The correspondence between classical and quantum mechanics is shown explicitly in the system. Numerical simulation shows that the temporal evolution of photodetached electronic wave packet on elastic surface exhibits some similar properties of time-resolved two-photon photoemission signal of surface electron.

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