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1.
Analyst ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639484

RESUMO

The conformation of proteins is closely related to their biological functions, and it is affected by many factors, including the type of cations in solution. However, it is difficult to detect the conformational changes of a protein in situ. As a single-molecule sensing technology, nanopores can convert molecular structural information into analyzable current signals within a reasonable time range. Herein, we detect and analyze the effects of two different types of monovalent cations (Na+ and Li+) on a model protein bovine serum albumin (BSA) conformation using SiNx nanopores with different diameters. The quantitative analysis results show that the excluded volume of BSA in LiCl salt solutions is larger than the value in NaCl solution, indicating that Li+ is more prone to unfolding the proteins and making them unstable. This study demonstrated that nanopores enable the in situ detection of the structure of proteins at the single-molecule level and provide a new approach for the quantitative analysis of proteins.

2.
Langmuir ; 40(11): 5799-5808, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501264

RESUMO

Nanopores are powerful single-molecule sensors for analyzing biomolecules such as DNA and proteins. Understanding the dynamics of DNA capture and translocation through nanopores is essential for optimizing their performance. In this study, we examine the effects of applied voltage and pore diameter on current blockage, translocation time, collision, and capture location by translocating λ-DNA through 5.7 and 16 nm solid-state nanopores. Ionic current changes are used to infer DNA conformations during translocation. We find that translocation time increases with pore diameter, which can be attributed to the decrease of the stall force. Linear and exponential decreases of collision frequency with voltage are observed in the 16 and 5.7 nm pores, respectively, indicating a free energy barrier in the small pore. Moreover, the results reveal a voltage-dependent bias in the capture location toward the DNA ends, which is explained by a "pulley effect" deforming the DNA as it approaches the pore. This study provides insights into the physics governing DNA capture and translocation, which can be useful for promoting single-file translocation to enhance nanopore sensing.


Assuntos
Nanoporos , DNA , Nanotecnologia/métodos , Transporte de Íons , Conformação de Ácido Nucleico
3.
Front Immunol ; 15: 1337105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481992

RESUMO

Background: The molecular mechanisms of hepatic fibrosis (HF), closely related to autophagy, remain unclear. This study aimed to investigate autophagy characteristics in HF. Methods: Gene expression profiles (GSE6764, GSE49541 and GSE84044) were downloaded, normalized, and merged. Autophagy-related differentially expressed genes (ARDEGs) were determined using the limma R package and the Wilcoxon rank sum test and then analyzed by GO, KEGG, GSEA and GSVA. The infiltration of immune cells, molecular subtypes and immune types of healthy control (HC) and HF were analyzed. Machine learning was carried out with two methods, by which, core genes were obtained. Models of liver fibrosis in vivo and in vitro were constructed to verify the expression of core genes and corresponding immune cells. Results: A total of 69 ARDEGs were identified. Series functional cluster analysis showed that ARDEGs were significantly enriched in autophagy and immunity. Activated CD4 T cells, CD56bright natural killer cells, CD56dim natural killer cells, eosinophils, macrophages, mast cells, neutrophils, and type 17 T helper (Th17) cells showed significant differences in infiltration between HC and HF groups. Among ARDEGs, three core genes were identified, that were ATG5, RB1CC1, and PARK2. Considerable changes in the infiltration of immune cells were observed at different expression levels of the three core genes, among which the expression of RB1CC1 was significantly associated with the infiltration of macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell. In the mouse liver fibrosis experiment, ATG5, RB1CC1, and PARK2 were at higher levels in HF group than those in HC group. Compared with HC group, HF group showed low positive area in F4/80, IL-17 and CD56, indicating decreased expression of macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell. Meanwhile, knocking down RB1CC1 was found to inhibit the activation of hepatic stellate cells and alleviate liver fibrosis. Conclusion: ATG5, RB1CC1, and PARK2 are promising autophagy-related therapeutic biomarkers for HF. This is the first study to identify RB1CC1 in HF, which may promote the progression of liver fibrosis by regulating macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell.


Assuntos
Cirrose Hepática , Macrófagos , Camundongos , Animais , Fibrose , Macrófagos/patologia , Autofagia/genética , Aprendizado de Máquina
4.
Lab Med ; 55(1): 71-79, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-37253164

RESUMO

OBJECTIVE: The aim of this study was to evaluate the efficacy of metagenomic next-generation sequencing (mNGS) for the identification of Gram-negative bacteria (GNB) infections and the prediction of antimicrobial resistance. METHODS: A retrospective analysis was conducted on 182 patients with diagnosis of GNB infections who underwent mNGS and conventional microbiological tests (CMTs). RESULTS: The detection rate of mNGS was 96.15%, higher than CMTs (45.05%) with a significant difference (χ 2 = 114.46, P < .01). The pathogen spectrum identified by mNGS was significantly wider than CMTs. Interestingly, the detection rate of mNGS was substantially higher than that of CMTs (70.33% vs 23.08%, P < .01) in patients with but not without antibiotic exposure. There was a significant positive correlation between mapped reads and pro-inflammatory cytokines (interleukin-6 and interleukin-8). However, mNGS failed to predict antimicrobial resistance in 5 of 12 patients compared to phenotype antimicrobial susceptibility testing results. CONCLUSIONS: Metagenomic next-generation sequencing has a higher detection rate, a wider pathogen spectrum, and is less affected by prior antibiotic exposure than CMTs in identifying Gram-negative pathogens. The mapped reads may reflect a pro-inflammatory state in GNB-infected patients. Inferring actual resistance phenotypes from metagenomic data remains a great challenge.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Humanos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Estudos Retrospectivos , Sequenciamento de Nucleotídeos em Larga Escala , Citocinas , Sensibilidade e Especificidade
5.
Biol Reprod ; 109(5): 635-643, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37658763

RESUMO

We previously demonstrated that MnCl2 induces double-stranded DNA breaks in sperm in a process that we term as sperm chromatin fragmentation. Here, we tested if the levels of double-stranded DNA breaks were corelated to the concentration of MnCl2, and we compared this to another agent that causes single-stranded DNA breaks, H2O2. We found that both methods have the advantage of inducing DNA breaks in a concentration-dependent manner. Mouse sperm were treated with varying concentrations of either H2O2 or MnCl2, and the DNA damage was assessed by pulse-field gel electrophoresis, and the alkaline and neutral comet assays. Oocytes were injected with either treated sperm and the resulting embryos analyzed with an embryoscope to detect subtle changes in embryonic development. We confirmed that H2O2 treatment induced primarily single-stranded DNA breaks and MnCl2 induced primarily double-stranded DNA breaks, indicating different mechanisms of damage. These sperm were injected into oocytes, and the development of the resulting embryos followed with an embryoscope equipped with time lapse recording. We found that aberrations in early embryonic development by day 2 with even the lowest levels of DNA damage and that the levels of embryonic aberrations correlated to the concentration of either H2O2 or MnCl2. Low levels of H2O2 caused significantly more aberrations in embryonic development than low levels of MnCl2 even though the levels of DNA damage as measured by comet assays were similar. These data demonstrate that even low levels of sperm DNA damage cause delays and arrests in embryonic development.


Assuntos
Cromatina , Peróxido de Hidrogênio , Animais , Feminino , Masculino , Camundongos , Gravidez , Dano ao DNA , Fragmentação do DNA , Desenvolvimento Embrionário/genética , Peróxido de Hidrogênio/toxicidade , Sêmen , Espermatozoides
6.
Infect Drug Resist ; 16: 1815-1828, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37016633

RESUMO

Purpose: Metagenomic next-generation sequencing (mNGS) is a powerful yet unbiased method to identify pathogens in suspected infections. However, little is known about its clinical effectiveness. The present study aimed to assess the efficacy of mNGS in routine clinical practice. Patients and Methods: In this single-center retrospective cohort study, 518 patients with suspected infectious diseases were assessed for inclusion. Among them, each patient had undergone mNGS testing; 407 patients had undergone both microbial culture and mNGS testing. The result of mNGS testing was compared to microbial culture performed concurrently. The diagnostic performance of mNGS was evaluated using the comprehensive clinical diagnosis as the reference standard. Results: There was a significant difference in the positive detection rates of pathogens between mNGS and culture (331/407, 81.3% vs 79/407, 19.4%, P < 0.001). The sensitivity of mNGS was much higher than the culture method (79.5% vs 21.3%, P < 0.001), especially in sample types of sputum and bronchoalveolar lavage fluid (BALF). Notably, the sensitivity of blood mNGS was relatively lower than other sample types (67.4% vs 88.9-93.8%). Pathogen cfDNA load based on standardized stringently mapped read number at the species level of microorganisms (SDSMRN) was significantly lower in blood than in other sample types from the same patient (P = 0.0003). Importantly, mNGS directly led to a change of treatment regimen in 142 (27.4%) cases, including antibiotic escalation (15.3%), antibiotic de-escalation (9.1%), and early definitive diagnosis to initiate appropriate treatment (3.1%). Conclusion: Our in-house mNGS platform significantly improved the sensitivity for the diagnosis of infectious diseases. mNGS has the potential to improve clinical outcomes by optimizing antimicrobial therapy.

7.
Results Probl Cell Differ ; 70: 295-311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36348112

RESUMO

Sperm nuclei present a highly organized and condensed chromatin due to the interchange of histones by protamines during spermiogenesis. This high DNA condensation leads to almost inert chromatin, with the impossibility of conducting gene transcription as in most other somatic cells. The major chromosomal structure responsible for DNA condensation is the formation of protamine-DNA toroids containing 25-50 kilobases of DNA. These toroids are connected by toroid linker regions (TLR), which attach them to the nuclear matrix, as matrix attachment regions (MAR) do in somatic cells. Despite this high degree of condensation, evidence shows that sperm chromatin contains vulnerable elements that can be degraded even in fully condensed chromatin, which may correspond to chromatin regions that transfer functionality to the zygote at fertilization. This chapter covers an updated review of our model for sperm chromatin structure and its potential functional elements that affect embryo development.


Assuntos
Cromatina , Sêmen , Masculino , Humanos , Sêmen/metabolismo , Cromatina/metabolismo , Espermatozoides/metabolismo , Protaminas/metabolismo , DNA/química
8.
Mol Hum Reprod ; 29(9)2022 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-35929777

RESUMO

Vasectomy is a widely used surgical technique creating an obstructive azoospermia. Although sperm cannot be ejaculated, the testis maintains sperm production in vasectomized males. The continuous accumulation of sperm deposited in the epididymis and the vas deferens fraction necessarily need to be degraded and eliminated. While the elimination process is carried out by granulomas that form after vasectomy, the detailed mechanisms of sperm degradation are still not known. The aim was to assess whether sperm chromatin fragmentation (SCF), a mechanism that degrades the entire sperm genome at the toroid linker regions (TLRs), is activated after vasectomy in sperm cells. We vasectomized mice and evaluated the presence of TLR-specific double-strand breaks through pulsed-field gel electrophoresis and the Comet assay at 1, 2 and 3 weeks after surgery. Results for DNA damage (Olive tail moment) at single-cell level showed an increase of double-strand breaks after vasectomy for vas deferens sperm after 1, 2 and 3 weeks postvasectomy (21.78 ± 2.29; 19.71 ± 1.79 and 32.59 ± 1.81, respectively), compared to mock surgery (7.04 ± 1.03; 10.10 ± 1.29 and 8.64 ± 0.85, respectively; P < 0.001). Similar findings were obtained for cauda epididymis sperm (P < 0.001), but not for caput epididymis (P > 0.05). Pulsed-field gel electrophoresis showed the presence of double-stranded breaks between 15 and 145 kb, indicating that DNA breaks were produced mainly in the sperm TLRs. Results presented here suggest that SCF is a mechanism activated in vas deferens after vasectomy to degrade sperm DNA when they cannot be ejaculated, preventing their function.


Assuntos
Vasectomia , Animais , Cromatina/genética , Cromatina/metabolismo , DNA , Quebras de DNA , Epididimo , Masculino , Camundongos , Sêmen , Espermatozoides , Ducto Deferente/metabolismo
9.
Biol Reprod ; 106(4): 730-740, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-34977916

RESUMO

Origin recognition complex subunit 4 (ORC4) is a DNA-binding protein required for DNA replication. During oocyte maturation, after the last oocyte DNA replication step and before zygotic DNA replication, the oocyte undergoes two meiotic cell divisions in which half the DNA is ejected in much smaller polar bodies. We previously demonstrated that ORC4 forms a cytoplasmic cage around the DNA that is ejected in both polar body extrusion (PBE) events. Here, we used ZP3 activated Cre to delete exon 7 of Orc4 during oogenesis to test how it affected both predicted functions of ORC4: its recently discovered role in PBE and its well-known role in DNA synthesis. Orc4 deletion severely reduced PBE. Almost half of Orc4-depleted germinal vesicle (GV) oocytes cultured in vitro were arrested before anaphase I (48%), and only 25% produced normal first polar bodies. This supports the role of ORC4 in PBE and suggests that transcription of the full-length Orc4 during oogenesis is required for efficient PBE. Orc4 deletion also abolished zygotic DNA synthesis. Fewer Orc4-depleted oocytes developed to the metaphase II (MII) stage, and after activation these oocytes were arrested at the two-cell stage without undergoing DNA synthesis. This confirms that transcription of full-length Orc4 after the primary follicle stage is required for zygotic DNA replication. The data also suggest that MII oocytes do not have a replication licensing checkpoint as cytokinesis progressed without DNA synthesis. Together, the data confirm that oocyte ORC4 is important for both PBE and zygotic DNA synthesis.


Assuntos
Complexo de Reconhecimento de Origem , Corpos Polares , Replicação do DNA , Meiose/genética , Oogênese/genética , Complexo de Reconhecimento de Origem/genética , Complexo de Reconhecimento de Origem/metabolismo
10.
Sports Health ; 14(3): 348-357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34399650

RESUMO

BACKGROUND: Remodeled bicycle pedal training with multidirectional challenges through muscle strengthening and neuromuscular facilitation may increase dynamic postural control and performance during lateral shuffling for athletes with functional ankle instability (FAI). HYPOTHESIS: The 6-week remodeled bicycle pedal training is effective on the ankle joint control and muscle activation, and especially that of the ankle evertor muscle co-contraction to improve dynamic postural control during lateral shuffling for athletes with FAI. STUDY DESIGN: Laboratory randomized controlled trial. LEVEL OF EVIDENCE: Level 2. METHODS: Fourteen healthy athletes (healthy group) and 26 athletes with FAI aged 18 to 30 years were included in the study. The athletes with FAI were randomly assigned to either the training group (FAI-T group) or the nontraining group (FAI-NT group). The athletes in the FAI-T group underwent 6 weeks of remodeled bicycle pedal training, whereas those in the FAI-NT group did not undergo any intervention. Muscle co-contraction index and muscle activation in the initial contact (IC) and propulsion phases, and ankle joint angle in the IC and propulsion phases were measured during lateral shuffling before and after 6 weeks of training. RESULTS: After remodeled bicycle pedal training, the FAI-T group demonstrated greater muscle activation in the hamstring (P = 0.01), greater muscle coactivation of the tibialis anterior (TA) and the peroneus longus (P = 0.01), and greater ankle eversion angle in the IC phase. Significantly greater muscle activation of the TA (P = 0.01), greater coactivation of quadriceps and hamstring (P = 0.03), and a smaller ankle inversion angle (P = 0.04) in the propulsion phase were observed in the FAI-T group after training compared with those in the FAI-NT group. CONCLUSION: Remodeled bicycle pedal training facilitates the TA and peroneus longus activation and the coactivation of the quadriceps and hamstring muscles during lateral shuffling and resulted in enhanced ankle and knee joint stability. In addition, a better ankle movement strategy during a dynamic task can be achieved via a 6-week remodeled pedal training program. CLINICAL RELEVANCE: This remodeled bicycle pedal training can be effective for rehabilitating athletes with FAI to recover lateral dynamic movement capability.


Assuntos
Tornozelo , Instabilidade Articular , Tornozelo/fisiologia , Articulação do Tornozelo , Atletas , Ciclismo , Humanos , Instabilidade Articular/terapia , Músculo Esquelético/fisiologia
11.
Reprod Health ; 18(1): 193, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593017

RESUMO

BACKGROUND: With the prevalence of infertility increasing every year around the world, it has seriously impacted the individual quality of family and social life. Anxiety is one of the most prevalent anxiety disorders among infertile patients. After the two-child policy, whether it affected the prevalence of anxiety is controversial. This study aimed to determine the prevalence of anxiety and its potential risk factors among Chinese infertile women after the enforcement of 'two-child policy'. METHODS: This cross-sectional study included 693 infertile patients in a reproductive medical center in Chongqing, China, between February 2016 and December 2018. Data was collected by Self-filling questionnaires including basic demographic information and the Generalized Anxiety Disorder-7 (GAD-7). SPSS statistical software (IBM SPSS version 25) was used to analyse the obtained data. Descriptive analysis was used to describe basic information and anxiety scores, the chi-square test and binary logistic regression were used to analyse the relationship between anxiety and other variables. RESULTS: The prevalence of anxiety among total infertile patients was 21.8%, and its 23.5% among first-child infertile patients (FI), and 18.4% among second-child infertile patients (SI) respectively (P > 0.05). Binary logistic regression showed that patients with lower education levels were more likely to have anxiety (P < 0.01). Patients with middle salary incomes were more likely to have anxiety (OR = 1.860, 95% CI: 1.068-3.238). Oral contraception taking history (OR = 1.778, 95% CI: 1.186-2.667), and history of allergy (OR = 2.098, 95% CI: 1.219-3.612) were associated with anxiety. CONCLUSIONS: Under the full liberalization of the "two-child policy", the total prevalence of anxiety among Chinese infertile female is comparatively high. Low education levels, middle incomes, oral contraception taking and allergy history can be the related risk factors of anxiety. We promote that all infertile patients should be evaluated for the prevalence of anxiety, especially those with potential risks, and receive consultant or targeted treatment when needed.


Assuntos
Infertilidade Feminina , Ansiedade/epidemiologia , Transtornos de Ansiedade/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Infertilidade Feminina/epidemiologia , Políticas , Prevalência
12.
Front Bioeng Biotechnol ; 8: 600187, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195176

RESUMO

CONTEXT: Appropriate training without risk of injury is a critical concern for athletes. Remodeled bicycle pedal training with multi-directional challenges may be effective in improving the balance performance of athletes with functional ankle instability (FAI). OBJECTIVE: To evaluate the effects of 6-week modified bicycle pedal training on the balance ability and proprioception of athletes with FAI. DESIGN: Randomized controlled trial. SETTING: University motion analysis laboratory. PARTICIPANTS: Fourteen healthy athletes (healthy group) and twenty-six athletes with FAI and an age of 18 to 30 years old. The participants with FAI were randomly distributed to two groups, designated as the training group (AI-T group) and non-training group (AI-NT group), respectively. The athletes in the AI-T group received 6-week remodeled bicycle pedal training, while those in the AI-NT group received no intervention at all. INTERVENTION: A 6-week training using modified bicycle pedal capable of moving freely during loading cycle vs no intervention. MAIN OUTCOME MEASURES: The passive ankle joint position sense (JPS) in four angles and the center of pressure (COP) parameters were analyzed during single-leg standing with and without vision, respectively. RESULTS: A 6-week remodeled pedal training: (1) significantly improved the passive JPS of ankle in all directions (P < 0.05); (2) reduced the excursion of the COP in the medial-lateral (ML) direction (p < 0.05), the velocity of the COP in the ML direction (p < 0.05), and the RMS of the COP in the ML direction (P < 0.05) during single-leg standing both with and without vision. CONCLUSION: The remodeled bicycle pedal training improved the passive JPS and reduced the postural sway in single-leg standing both with and without vision. Therefore, remodeled bicycle pedal training can be considered for inclusion in rehabilitation programs for athletes with FAI to restore the proprioception and balance ability.

13.
J Sport Rehabil ; 29(2): 200-205, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30676181

RESUMO

CONTEXT: Squats and lunges are common exercises frequently applied in muscle-strengthening and therapeutic exercises. The loading devices are often used to increase the training intensity. OBJECTIVE: To determine the effect of loading devices on muscle activation in squat and lunge and to compare the differences in muscle activation between squat and lunge. DESIGN: Cross-sectional cohort. PARTICIPANTS: Nineteen healthy, male, recreationally active individuals without a history of lower limb injury. INTERVENTIONS: Each participant performed 10 repetitions of a squat under 5 conditions: unloaded, barbell, dumbbell, loaded vest, and kettlebell, and 10 repetitions of a lunge under 4 conditions: unloaded, barbell, dumbbell, and loaded vest. MAIN OUTCOME MEASURES: The electromyography signals of quadriceps, hamstrings, tibialis anterior, gastrocnemius lateralis and medialis were measured. One-way repeated-measure analysis of variance was used to compare the difference among different loading conditions. Paired t test was used to compare the difference between squat and lunge. RESULTS: The muscle activation in the loaded conditions was significantly higher than that in nonloaded conditions in squat and lunge. Compared with the barbell, dumbbell, and loaded vest conditions, the semitendinosus showed significantly higher activation, and the tibialis anterior showed significantly lower activation in kettlebell condition in squat. No significant difference in muscle activation was found among barbell, dumbbell, and kettlebell conditions in lunge. In addition, quadriceps and hamstring activities were significantly higher in lunge than in squat. CONCLUSIONS: Muscle activation was affected by the loading devices in squat but not affected in lunge. Kettlebell squat could be suggested for targeting in strengthening medial hamstring. Progressive strengthening exercise could be recommended from squat to lunge based on sequential activation level.


Assuntos
Extremidade Inferior/fisiologia , Músculo Esquelético/fisiologia , Treinamento Resistido/instrumentação , Equipamentos Esportivos , Eletromiografia , Humanos , Masculino , Força Muscular , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-31528854

RESUMO

Vaginal endometrial stromal sarcoma (VESS) is a rare disease. To the best of our knowledge, there have only been a few reported cases in the literature. Therefore, we conducted a literature review to obtain specific knowledge of this disease. Thirteen cases of VESS were found by searching the Medline and EMBASE databases in the English language. The mechanism of VESS may be associated with endometriosis, and its diagnosis largely depends on pathological examination because it has no typical symptoms. Treatment of VESS incorporates surgery, chemotherapy, radiotherapy, and hormonal therapy. Some novel drugs targeting its mechanism may become alternative therapies. Its prognostic factors may include tumor stage and the expression of hormonal receptors.

15.
ACS Appl Mater Interfaces ; 10(31): 26555-26565, 2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30016075

RESUMO

The detection and investigation of biomolecules at a single-molecule level is important for improving diagnosis in biomedicine. Solid-state nanopores are a unique tool that have the potential to accomplish this task because they are label-free and require only low sample consumption. However, the event-readouts of current small polymer molecules are still limited because of its relatively large size and low signal-to-noise ratios. Here, we present a rapid sensing approach for the detection of GR-5 DNAzyme cleaving specific substrate reactions using relatively larger size silicon nitride nanopores by introducing a type of nucleic acid nanostructure (DNA tetrahedron) as a carrier. The proposed method is convenient and sensitive enough to detect the cleavage reactions by identifying translocation events before and after reactions with nanomolar concentrations of the target sample. Furthermore, this assay was also carried out by using larger size nanopores (60 nm diameter) to achieve the DNAzyme cleavage sensing with the same sample concentration. This approach can improve event detectability of other smaller molecules' translocation, which opens up a wide range of applications for analytes detection by incorporating solid-state nanopores. Nucleic acid nanostructure-assisted nanopore sensing can promote the development of single-molecule studies.


Assuntos
Nanoporos , DNA , DNA Catalítico , Nanoestruturas , Nanotecnologia , Razão Sinal-Ruído
16.
Oncol Lett ; 12(2): 983-988, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27446381

RESUMO

Cyclooxygenase-2 (COX-2) serves an important role in the carcinogenesis and progression of gastric cancer. Harmine (HM) and paclitaxel (PTX) are reported as promising drug candidates for cancer therapy, but whether a synergistic anti-tumor effect of HM combined with PTX exists in human gastric cancer remains unknown. The present study evaluated the effects of HM and/or PTX on cell proliferation and apoptosis in a gastric cancer cell line, SGC-7901. HM and PTX inhibited cell proliferation in a dose-dependent manner. Both HM and PTX alone induced apoptosis in gastric cancer cells. The combination of HM and PTX exerted synergistic effects on proliferation inhibition and apoptosis induction in SGC-7901 cells, with down-regulation of COX-2, PCNA and Bcl-2 and up-regulation of Bax expression. The results indicated that combination chemotherapy using HM with PTX exerts an anti-tumor effect for treating gastric cancer. The combination of the two drugs inhibits gastric cancer development more effectively than each drug alone through down-regulation of COX-2 expression.

17.
J Phys Ther Sci ; 28(5): 1614-20, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27313384

RESUMO

[Purpose] Tripping is a frequent cause of falls among aging adults. Appropriate limb movements while negotiating obstacles are critical to trip avoidance. The aim of our study was to investigate the mechanics of obstacle crossing in older adults at low or high risk of falling. [Subjects and Methods] Twenty community-dwelling adults aged ≥55 years, were evaluated with the Tinetti Balance and Gait scale and classified as being at high or low risk of falling. Between-group comparisons of kinematics were evaluated for obstacle heights of 10%, 20%, and 30% of leg length. [Results] The high-risk group demonstrated greater toe-obstacle clearance of the leading leg. Increasing obstacle height led to increased maximal toe-obstacle clearance, toe-obstacle distance, and shortened swing phase of the leading limb. Adaptation of clearance height was greater for the trailing leg. Individuals at high risk of falling demonstrated less symmetry between the leading and trailing legs and a narrower step width, features that increase the likelihood of tripping. [Conclusion] Kinematic parameters of obstacle clearance, including the symmetry index described in our study, could provide clinicians with a quick screening tool to identify patients at risk of falling and to evaluate outcomes of training programs.

18.
Nanoscale Res Lett ; 11(1): 50, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26831688

RESUMO

The nanopore sensor as a high-throughput and low-cost technology can detect single nanoparticle in solution. In the present study, the silicon nitride nanopores were fabricated by focused Ga ion beam (FIB), and the surface was functionalized with 3-aminopropyltriethoxysilane to change its surface charge density. The positively charged nanopore surface attracted negatively charged nanoparticles when they were in the vicinity of the nanopore. And, nanoparticle translocation speed was slowed down to obtain a clear and deterministic signal. Compared with previous studied small nanoparticles, the electrophoretic translocation of negatively charged polystyrene (PS) nanoparticles (diameter ~100 nm) was investigated in solution using the Coulter counter principle in which the time-dependent nanopore current was recorded as the nanoparticles were driven across the nanopore. A linear dependence was found between current drop and biased voltage. An exponentially decaying function (t d ~ e (-v/v0) ) was found between the duration time and biased voltage. The interaction between the amine-functionalized nanopore wall and PS microspheres was discussed while translating PS microspheres. We explored also translocations of PS microspheres through amine-functionalized solid-state nanopores by varying the solution pH (5.4, 7.0, and 10.0) with 0.02 M potassium chloride (KCl). Surface functionalization showed to provide a useful step to fine-tune the surface property, which can selectively transport molecules or particles. This approach is likely to be applied to gene sequencing.

19.
Environ Sci Pollut Res Int ; 23(9): 8827-36, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26810665

RESUMO

Haze from urban sites in Beijing was collected with a self-assembled electrostatic dust collector. The sizes and morphologies, thermal properties, and compositions of the particles in the haze were characterized by scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), and X-ray photoelectric spectroscopy (XPS), respectively. Based on these results, the causes and pollutant sources of the chemicals in the haze were analyzed, and some countermeasures were further advanced to reduce the related pollutant sources. Graphical abstract ᅟ.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Material Particulado/análise , Pequim , China , Poeira
20.
Anal Chem ; 88(4): 2502-10, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26790522

RESUMO

Nanopores have been used as a high throughput tool for characterizing individual biomolecules and nanoparticles. Here, we present the translocation of rigid rod-shaped tobacco mosaic virus (TMV) through solid-state nanopores. Interestingly, due to the high rigidity of TMV, three types of events with distinctive characteristics at the capture process and a strong current fluctuation during the translocation of TMV are observed. A kinetic model is then proposed to address the dynamics of the translocation, followed by corresponding dynamics simulations. The results reveal that TMV has to rotate to fit and pass the pore when it is captured by a nanopore with an angle larger than the maximum angle that allows it to pass through. Then, we investigate the dependence of the rotation of TMV on the conductance fluctuations at the blockade stage. The results show that the rotation of TMV during the passage through the pore affects the current signal significantly. This study gives a fundamental understanding of the dynamics of rod-shaped particles translocating through the nanopore and how the current responds to it. It opens a new possible way to characterize the rigidity of analytes by nanopores.


Assuntos
Nanoporos , Vírus do Mosaico do Tabaco/química , Vírus do Mosaico do Tabaco/isolamento & purificação , Tamanho da Partícula , Propriedades de Superfície
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