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1.
Environ Sci Technol ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31411864

RESUMO

Arsenic-hyperaccumulator Pteris vittata is efficient in As accumulation and has been used in phytoremediation of As-contaminated soils. Arsenate (AsV) is the predominant As species in aerobic soils and is taken up by plants via phosphate transporters (Pht) including P. vittata. In this work, we cloned the PvPht1;3 full length coding sequence from P. vittata and investigated its role in As accumulation by yeast and plants. PvPht1;3 complemented a yeast P uptake mutant strain and showed a stronger affinity and transport capacity to AsV than PvPht1;2. In transgenic tobacco, PvPht1;3 enhanced AsV absorption and translocation, increasing As accumulation in the shoots under both hydroponic and soil experiments. On the basis of the expression patterns via qRT-PCR, PvPht1;3 was strongly induced by P deficiency but not As exposure. To further understand its expression pattern, transgenic Arabidopsis thaliana and soybean expressing the GUS reporter gene, driven by PvPht1;3 promoter, were produced. The GUS staining showed that the reporter gene was mainly expressed in the stele cells, indicating that PvPht1;3 was expressed in stele cells and was likely involved in P/As translocation. Taken together, the data suggested that PvPht1;3 was a high-affinity AsV transporter and was probably responsible for efficient As translocation in P. vittata. Our results suggest that expressing PvPht1;3 enhances As translocation and accumulation in plants, thereby improving phytoremediation of As-contaminated soils.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31403243

RESUMO

A vancomycin steady-state trough concentration (Cmin ) of 15-20 mg/L is recommended for achieving a ratio of the 24-hour area under the curve to the minimum inhibitory concentration (AUC0-24 /MIC) of ≥400 in adults. Since few paediatric data are available, our objectives were to (a) measure the pharmacokinetic indices of vancomycin and (b) determine the correlation between Cmin and AUC0-24 /MIC in paediatric patients. Population-based pharmacokinetic modelling was performed for paediatric patients to estimate the individual parameters. The relationship between Cmin and the calculated AUC0-24 /MIC was explored using linear regression and a probabilistic framework. A sensitivity analysis was also conducted using Monte Carlo simulations. Body-weight significantly influenced the pharmacokinetics of vancomycin. Based on real data and simulations, Cmin ranges of 5.0-5.9 and 9.0-12.9 mg/L were associated with AUC0-24 /MIC ≥400 for MIC values of ≤0.5 and ≤1 mg/L, respectively. Vancomycin regimens of 10 and 15 mg/kg every 6 hours achieved a Cmin of 5.0-5.9 mg/L and AUC0-24 /MIC ≥400 in >90% of the children when MIC was ≤0.5 mg/L. At a MIC of ≤1 mg/L, vancomycin at 15 mg/kg every 6 hours achieved Cmin of 9.0-12.9 mg/L and AUC0-24 /MIC ≥400 in 2.0- and 1.6-fold as many children compared to a dose of 10 mg/kg every 6 hours, respectively. Vancomycin Cmin values of 5.0-12.9 mg/L were strongly predictive of achieving AUC0-24 /MIC ≥400, and rational dosing regimens of 10-15 mg/kg q6h were required in paediatric patients, depending on the pathogen.

3.
Diabetes ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439648

RESUMO

CCR2 has been proved to play an important role in diabetes. However, the role of CCR2 in diabetic cardiomyopathy has not been examined. In this study, we investigated the effects of cardiac CCR2 on diabetic cardiomyopathy. We created streptozotocin (STZ)-induced diabetic cardiomyopathy model. Expression of CCR2 were up-regulated in STZ-induced diabetic hearts. CCR2 knockout (CCR2 KO) significantly improved STZ-induced cardiac dysfunction and fibrosis. Moreover, deletion of CCR2 inhibited the STZ induced the apoptosis as well as the production of STZ-induced reactive oxygen species (ROS) in the heart. CCR2 knockout resulted in M2 polarization in heart from STZ treated-mice. Meantime, CCR2 inhibitor treatment also reversed hyperglycemia induced cardiac dysfunction in db/db mice. Our results suggested that cardiac CCR2-induced inflammation and oxidative stress are involved in the development of diabetic cardiomyopathy and CCR2 could be a novel target for therapy.

4.
J Clin Pharm Ther ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31468555

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Caspofungin is commonly used in kidney transplant patients for prophylaxis or treatment of invasive fungal infections (IFIs) caused by Candida spp. and Aspergillus spp. Factors such as concomitant medications, co-morbidity and rejection often cause caspofungin pharmacokinetic parameters alterations in kidney transplant patients. Here, we aimed to investigate factors influencing caspofungin plasma concentrations and evaluate its prophylaxis and treatment efficiency for IFIs in kidney transplant patients. METHODS: The prophylaxis and treatment efficiency of caspofungin for IFIs were assessed in 164 kidney transplant patients in the study. Six hundred and fifty-two caspofungin trough concentrations (Cmin ) from the 164 patients were monitored by the liquid chromatography-tandem mass spectrometry method. Basic demographic variables, baseline disease, surgery, rejection, indwelling catheter, coinfection, concomitant medication and other caspofungin-related factors were collected. Univariate and multivariate analyses were used to assess factors influencing caspofungin plasma concentrations. RESULTS AND DISCUSSION: The success rates were 94.96% (132/139) for caspofungin prevention and 80% (20/25) for caspofungin for IFIs. Caspofungin Cmin in the kidney recipients varied largely compared with healthy volunteers (0.10-12.25 mg/L vs. 1.12-1.78 mg/L). Caspofungin Cmin significantly increased in patients with continuous renal replacement therapy before transplantation (P = .001), concomitant medication of cyclosporine A (CsA, P = .009), ALB concentration of > 30 g/L (P = .019). WHAT IS NEW AND CONCLUSION: This is an uncontrolled observational study of caspofungin as prophylaxis or treatment for IFIs in kidney transplant patients. Caspofungin could be an effective and well-tolerated option for antifungal prophylaxis and treatment in kidney transplant patients, and a number of factors could influence caspofungin Cmin in these patients.

5.
Theranostics ; 9(16): 4704-4716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367251

RESUMO

Hepatocellular carcinoma (HCC) is in an urgent need of new, effective therapies to reduce morbidity and mortality. We have previously demonstrated that peptidyl-prolyl cis/trans isomerase Pin1 is a potential target for HCC therapy, due to its pivotal role in HCC development through regulating miRNA biogenesis, and discovered the small molecule API-1 as a novel and specific Pin1 inhibitor. Despite its significant anti-HCC activity, the low water solubility and in vivo bioavailability of API-1 limit its clinical application. To address these issues, we herein developed a liposomal formulation of API-1 to improve API-1 delivery and enhance its anti-HCC efficacy. Methods: We designed and developed a nanoscale liposomal formulation of API-1, named as API-LP. Subsequently, the mean diameter, polydispersity, zeta potential, encapsulation efficiency and thermal properties of the optimization API-LP were characterized. The enhanced anti-HCC activity and the molecular mechanism of API-LP were investigated both in vitro and in vivo. Finally, the safety and pharmacokinetic property of API-LP were evaluated systematically. Results: API-LP had good formulation characteristics and exhibited an enhanced in vitro activity of suppressing proliferation and migration of HCC cells when compared with free API-1. The mechanism study showed that API-LP upregulated miRNA biogenesis via inhibiting Pin1 activity followed by restoring the nucleus-to-cytoplasm export of XPO5. Because of the increased delivery efficiency, API-LP displayed a stronger ability to promote miRNA biogenesis than free API-1. Importantly, API-LP displayed higher systemic exposure than free API-1 in mice without apparent toxicity, resulting in an enhanced tumor inhibition in xenograft mice. Conclusion: The development and assessment of API-LP provide an attractive and safe anti-HCC agent, highlighting the miRNA-based treatment for human cancers.

6.
Pest Manag Sci ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31359575

RESUMO

BACKGROUND: Rapid evolution of pest resistance has seriously threatened the sustainable use of Bacillus thuringiensis (Bt). The diamondback moth, Plutella xylostella (L.), is the first pest to develop resistance to Bt biopesticides in the open field, which renders it an excellent model to explore the molecular basis of Bt resistance in insects. Our previous midgut transcriptome and RNA-Seq profiles showed that the P-glycoprotein gene PxABCB1 was down-regulated in two Cry1Ac-resistant P. xylostella strains, suggesting its potential involvement in Cry1Ac resistance in P. xylostella. RESULTS: In this study, the bona fide full-length cDNA sequence of the PxABCB1 gene was cloned and analyzed, and the expression of the PxABCB1 gene was detected in all tissues and developmental stages, with the highest expression in midgut tissue and the female adult stage. Although no consistent non-synonymous mutations were identified between the susceptible and resistant strains, PxABCB1 gene expression was remarkably decreased in all resistant strains, and the association was further validated by Cry1Ac selection in the moderately resistant SZ-R strain. Moreover, knockdown of the PxABCB1 gene expression resulted in significantly reduced larval susceptibility to Cry1Ac toxin in the DBM1Ac-S strain, and decreased expression of the PxABCB1 gene was tightly linked to Cry1Ac resistance in P. xylostella. CONCLUSION: Our results demonstrated that down-regulation of the PxABCB1 gene is associated with both laboratory-selected and field-evolved Cry1Ac resistance in P. xylostella. This knowledge will be conducive to further elucidating the complicated molecular basis of Bt resistance and developing new insect resistance management tactics. © 2019 Society of Chemical Industry.

7.
ACS Appl Mater Interfaces ; 11(30): 27269-27278, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31260238

RESUMO

Through a nature-inspired layer-by-layer assembly process, we developed a unique multifunctional tissue scaffold that consists of porous polyurethane substrate and nanoscale chitosan/graphene oxide hybrid coating. Alternative layers of drug-laden chitosan and graphene oxide nanosheets were held together through strong electrostatic interaction, giving rise to a robust multilayer architecture with control over structural element orientation and chemical composition at nanoscale. Combined pH-controlled co-delivery of multiple therapeutic agents and photothermal therapy has been achieved by our scaffold system. The new platform technology can be generalized to produce other tissue scaffold systems and may enable potential multimodal therapeutic applications such as bone cancer managements.

8.
Cell Rep ; 28(2): 512-525.e6, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31291585

RESUMO

Drug resistance is a significant hindrance to effective cancer treatment. Although resistance mechanisms of epidermal growth factor receptor (EGFR) mutant cancer cells to lethal EGFR tyrosine kinase inhibitors (TKI) treatment have been investigated intensively, how cancer cells orchestrate adaptive response under sublethal drug challenge remains largely unknown. Here, we find that 2-h sublethal TKI treatment elicits a transient drug-tolerant state in EGFR mutant lung cancer cells. Continuous sublethal treatment reinforces this tolerance and eventually establishes long-term TKI resistance. This adaptive process involves H3K9 demethylation-mediated upregulation of branched-chain amino acid aminotransferase 1 (BCAT1) and subsequent metabolic reprogramming, which promotes TKI resistance through attenuating reactive oxygen species (ROS) accumulation. Combination treatment with TKI- and ROS-inducing reagents overcomes this drug resistance in preclinical mouse models. Clinical information analyses support the correlation of BCAT1 expression with the EGFR TKI response. Our findings reveal the importance of BCAT1-engaged metabolism reprogramming in TKI resistance in lung cancer.

9.
Life Sci ; 232: 116609, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31254585

RESUMO

Pioglitazone has been demonstrated to exert anti-fibrotic and renoprotective effects. But the detailed pharmacological mechanisms have not been clearly revealed. The present study aimed to investigate the possible mechanisms of pioglitazone in these two effects. TGF-ß1-stimulated HK-2 cells and unilateral ureteral obstruction (UUO) mice were used as in vitro and in vivo models. The results showed that pioglitazone inhibited Smad-2/3 phosphorylation, upregulated Smad-7 expression and downregulated miR-21-5p expression in TGF-ß1-exposed HK-2 cells. In addition, miR-21-5p inhibitors replicated the anti-fibrotic effects of pioglitazone, and miR-21-5p mimics inhibited these effects. In in vivo study, pioglitazone attenuated UUO-induced renal fibrosis and significantly decreased the expressions of pro-fibrotic proteins. Whereas, agomir of miR-21-5p inhibited the renoprotective function of pioglitazone in UUO mice. In conclusion, the present data suggest that modulation of miR-21-5p/Smad-7 signal may be involved in the anti-fibrotic effect of pioglitazone in the kidney of UUO mice.

10.
Cell Signal ; 62: 109334, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31158467

RESUMO

Renal aging and associated functional decline are associated with an increase in cellular senescence. Previous studies show a direct correlation between advanced glycation end products (AGEs) accumulation and renal aging, chronic kidney disease (CKD) and other nephropathies, although the underlying molecular mechanisms remain largely unclear. We found elevated levels of the receptor of advanced glycation end product (RAGE) as well as STAT5 in aged human kidneys, as well as in human mesangial cells aged artificially through AGEs. Furthermore, genetic and pharmacological ablation of STAT5 significantly downregulated p16 levels and the percentage of ß-Gal-positive senescent cells in mesangial cells and kidneys of SD rats, indicating that AGEs-induced senescence depends on STAT5 signaling. The aged kidney tissues (both in patients and SD rats) and mesangial cells show low levels of LC3 (both LC3-II and LC3-II/I), and cultured mesangial cells also show fewer autolysosomes, autophagosomes, and autophagic vacuoles, which can be partially restored upon STAT5 inhibition. This indicates that AGEs accumulation also obliterates the protective effects of autophagy against aging via the RAGE/STAT5 axis. Direct inhibition of autophagy via 3-methyladenine (3-MA) increases the phenotype of renal aging without activating RAGE, it is inhibition of autophagy caused by RAGE/STAT5 that leads to mesangial aging. In conclusion, we found AGEs induced inhibition of autophagy and cellular senescence in mesangial cells via the RAGE/STAT5 pathway. Moreover, we found that RAGE/STAT5 acts as a key link between autophagy and senescence in the process of mesangial aging in vivo and in vitro.

11.
Zhongguo Zhen Jiu ; 39(6): 609-12, 2019 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-31190497

RESUMO

OBJECTIVE: To observe the effect of intradermal needing combined with rehabilitation intervention on middle and early knee osteoarthritis. METHODS: Seventy patients were randomly divided into an observation group and a control group, 35 cases in each group. Excluding the dropping cases, finally, 34 cases in the observation group and 32 cases in the control group were included in the statistics. Intradermal needing combined with rehabilitation intervention were given in the observation group, the intradermal needing was applied at Dubi (ST 35), Neixiyan (EX-LE 8), Xuehai (SP 10), Liangqiu (ST 34), Yanglingquan (GB 34), ashi point, and retained for 24 h; the simple conventional rehabilitation intervention was given in the control group. The visual analogue scale (VAS) was used to evaluate knee pain before treatment, the end of initial treatment, 1 month after treatment, and 3 months after treatment. The Western Ontario and McMaster Osteoarthritis index (WOMAC) was used to assess the joint function of the knee, the active knee flexion range (ROM) was used to assess the joint mobility of the knee before treatment and 1 month after treatment, and the efficacy of the two groups was evaluated. RESULTS: At the end of the initial treatment, the VAS score in the observation group were significantly improved as compared with that before treatment and the control groups (P<0.05), but there was no significant difference in the control group compared with that before treatment (P>0.05). After 1 month of treatment, the VAS score, WOMAC score and ROM measurement in the two groups were significantly improved as compared with those before treatment (P<0.05), and the observation group was superior to the control group (P<0.05); the total effective rate in the observation group was 97.1% (33/34), which was better than 81.3% (26/32) in the control group (P<0.05). At the follow-up, the VAS scores in the two groups were slightly higher than those after 1 month of treatment, but the difference was still statistically significant as compared with those before treatment (P<0.05), and the observation group was still superior to the control group (P<0.05). CONCLUSION: The combination of intradermal needing combined with rehabilitation intervention can effectively alleviate knee pain and improve joint function. It has a beneficial effect on the rehabilitation of middle and early knee osteoarthritis.


Assuntos
Terapia por Acupuntura , Moxibustão , Osteoartrite do Joelho , Pontos de Acupuntura , Humanos , Osteoartrite do Joelho/terapia , Resultado do Tratamento
12.
Nanotechnology ; 30(45): 455603, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31207585

RESUMO

This is the first study on the deployment of direct current atmospheric pressure microplasma technique for the single step synthesis of gold nanoparticle/graphene oxide (AuNP/GO) nanocomposites. The nanocomposites were characterized using ultraviolet-visible spectroscopy (UV-vis), x-ray diffraction and x-ray photoelectron spectroscopy and their formation mechanisms have been discussed in detail. Our AuNP/GO nanocomposites are highly biocompatible and have demonstrated surface enhanced Raman scattering (SERS) properties as compared to pure AuNPs and pure GO. Their potential as SERS substrate has been further demonstrated using probe molecules (methylene blue) at different concentrations.

13.
Nat Commun ; 10(1): 2522, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175310

RESUMO

The discovery of superconductivity at 260 K in hydrogen-rich compounds like LaH10 re-invigorated the quest for room temperature superconductivity. Here, we report the temperature dependence of the upper critical fields µ0Hc2(T) of superconducting H3S under a record-high combination of applied pressures up to 160 GPa and fields up to 65 T. We find that Hc2(T) displays a linear dependence on temperature over an extended range as found in multigap or in strongly-coupled superconductors, thus deviating from conventional Werthamer, Helfand, and Hohenberg (WHH) formalism. The best fit of Hc2(T) to the WHH formalism yields negligible values for the Maki parameter α and the spin-orbit scattering constant λSO. However, Hc2(T) is well-described by a model based on strong coupling superconductivity with a coupling constant λ ~ 2. We conclude that H3S behaves as a strong-coupled orbital-limited superconductor over the entire range of temperatures and fields used for our measurements.

14.
J Cell Physiol ; 234(12): 22623-22634, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31106426

RESUMO

Cystatin SN, a specific cysteine protease inhibitor, is thought to be involved in various malignant tumors. Therefore, we evaluated the role of cystatin SN in hepatocellular carcinoma (HCC). Notably, cystatin SN was elevated in tumorous samples and cells. Moreover, overexpression of cystatin SN was correlated with tumor diameter and TNM stage. Cox multivariate analysis displayed that cystatin SN was an independent prognosis indicator and that high cystatin SN level was associated with a dismal prognosis. Moreover, cystatin SN enhancement facilitated the proliferation, migratory, and invasive potential of Huh7 and HCCLM3 cells, whereas cystatin SN knockdown caused the opposite effect. Cystatin SN also modulated the epithelial-mesenchymal transition progression through the PI3K/AKT pathway. In vivo cystatin SN promoted HCCLM3 cell growth and metastasis in xenograft mice model. Thus, cystatin SN was involved in HCC progression and could be a latent target for HCC treatment.

15.
Mikrochim Acta ; 186(6): 367, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31115772

RESUMO

A high-throughput, dual-channel single cell analytical method is described for the detection of sialic acid (SA) on single cell based on the use of microfluidic droplets integrated with plasmonic imaging and surface-enhanced Raman spectroscopy (SERS) with the assistance of a multifunctional metal nanoparticle-based probe. The multifunctional plasmonic nanoprobe was prepared by modifying silver nanoparticles (AgNPs) with 4-mercaptophenylboronic acid (MPBA) that both warrants SA recognition and acts as a Raman reporter. This nanoprobe is a high-contrast indicator under bright field imaging due to the strong energy loss feature of AgNPs, and also owns possesses a strong SERS enhancement capability toward MPBA. Cells incubated with the plasmonic nanoprobes were isolated in water-in-oil droplets and then were re-dispersed in a chamber array chip. High-precision profiles of SA on a single cell in one droplet were obtained by the bright field imaging and image processing. The SA expression levels on different cell lines (MCF-7, HepG2, SGC and BNL.CL2) traced by SERS spectroscopy were compared. The statistical data among different cell lines confirm that the SA expression levels on cancer cells are much higher than that on normal cells. Single cell analysis further revealed that the cell-to-cell variations are more obvious in cancer cell lines. This study provides a valuable tool for understanding glycan-related biochemical processes. Graphical abstract A high-throughput, dual-channel microfluidic droplet platform succeeded in distinguishing different cancer cell lines at single living cell level integrated with plasmonic imaging and surface-enhanced Raman spectroscopy with assistance of a multifunctional metal nanoparticle-based probe.

16.
Medicine (Baltimore) ; 98(20): e15733, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096533

RESUMO

BACKGROUND: Antiphospholipid syndrome (APS) is a rare heterogenous autoimmune disorder with severe life-threatening complications shown during pregnancy. In this analysis, we aimed to systematically compare the pregnancy outcomes (both maternal and fetal) in patients with APS. METHODS: Web of Science, Google Scholar, Medicus, Cochrane Central, Embase, and Medline were searched for relevant English publications. The main inclusion criteria were based on studies that compared pregnancy outcomes in patients with APS vs a control group. Statistical analysis was carried out by the RevMan software version 5.3. This analysis involved dichotomous data, and risk ratios (RR) with 95% confidence intervals (CIs) were used to represent the analysis. RESULTS: Eight studies consisting of a total number of 212,954 participants were included. Seven hundred seventy participants were pregnant women with APS and 212,184 participants were assigned to the control group. Pregnancy-induced hypertension was significantly higher in women with APS (RR: 1.81, 95% CI: 1.33 - 2.45; P = .0002). The risks of fetal loss (RR: 1.33, 95% CI: 1.00-1.76; P = .05), abortion (RR: 2.42, 95% CI: 1.46-4.01; P = .0006), thrombosis (RR: 2.83, 95% CI: 1.47-5.44; P = .002), and preterm delivery (RR: 1.89, 95% CI: 1.52-2.35; P = .00001) were also significantly higher in women with APS. However, placental abruption (RR: 1.35, 95% CI: 0.78-2.34; P = .29) and pulmonary embolism were not significantly different (RR: 1.47, 95% CI: 0.11-19.20; P = .77). The risk of neonatal mortality (RR: 3.95, 95% CI: 1.98-7.86; P = .0001), infants small for gestational age (RR: 1.38, 95% CI: 1.04-1.82; P = .02), premature infants (RR: 1.86, 95% CI: 1.52-2.28; P = .0001), and infants who were admitted to neonatal intensive care unit (RR: 3.35, 95% CI: 2.29-4.89; P = .00001) were also significantly higher in women with APS. CONCLUSION: This analysis showed APS to be associated with significantly worse pregnancy outcomes when compared to the control group. A significantly higher risk of maternal and fetal complications was observed in this category of patients. Therefore, intense care should be given to pregnant women with APS to monitor unwanted outcomes and allow a successful pregnancy.


Assuntos
Síndrome Antifosfolipídica/complicações , Complicações na Gravidez/epidemiologia , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Síndrome Antifosfolipídica/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/etiologia , Lactente , Mortalidade Infantil , Recém-Nascido Prematuro , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Complicações na Gravidez/classificação , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia
17.
Chem Commun (Camb) ; 55(46): 6551-6554, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31106804

RESUMO

Sodium titanate nanosheet arrays grown on titanium foil are utilized as a current collector for a lithium metal anode and Ti3+ is introduced by Ar/H2 plasma for a uniform lithium deposition. The lithium nucleation overpotential and voltage hysteresis are dramatically reduced by increased active sites and improved electrical conductivity.

18.
Mol Cancer ; 18(1): 74, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940133

RESUMO

tRNA-derived small RNA (tsRNA) is a novel regulatory small non-coding RNA and participates in diverse physiological and pathological processes. However, the presence of tsRNAs in exosome and their diagnostic potential remain unclear. In this study, we took advantage of small RNA-seq technology to profile exosomal tsRNAs from cell culture medium and plasma, and found ubiquitous presence of tsRNAs in exosome. To explore the potential value of tsRNA for cancer diagnosis, we compared exosomal tsRNA levels between liver cancer patients and healthy donors, revealing that tsRNAs were dramatically increased in plasma exosomes of liver cancer patients. Importantly, patients with liver cancer exhibited significantly higher levels of four tsRNAs (tRNA-ValTAC-3, tRNA-GlyTCC-5, tRNA-ValAAC-5 and tRNA-GluCTC-5) in plasma exosome, demonstrating that plasma exosomal tsRNA could serve as a novel diagnostic biomarker. Taken together, our results not only expand non-coding RNA species in exosome, but also highlight the potential of tsRNAs as a promising biomarker for cancer diagnosis.


Assuntos
Exossomos/genética , Neoplasias/diagnóstico , RNA de Transferência/genética , RNA não Traduzido/genética , Biomarcadores Tumorais/genética , Técnicas de Cultura de Células , Detecção Precoce de Câncer , Humanos , Neoplasias/genética , Análise de Sequência de RNA , Células Tumorais Cultivadas
19.
J Pediatr Orthop ; 39(5): 257-262, 2019 May/Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30969256

RESUMO

BACKGROUND: Blount disease is a disorder of the posteromedial proximal tibial physis which causes a progressive varus, procurvatum, and internal rotation deformity of the tibia. Untreated, it can cause significant limb malalignment. The goal of this study is to evaluate the results of correction of Blount disease using types of external fixation. METHODS: We conducted a retrospective review of 41 patients (51 limbs) who underwent correction of Blount disease with an Ilizarov external fixator or a Taylor spatial frame (TSF) by a single surgeon. The medial proximal tibial angle (MPTA), mean axis deviation (MAD), posterior proximal tibial angle, and joint line congruence angle (JLCA) were measured on radiographs preoperatively, at frame removal and at final follow-up. RESULTS: The average age at treatment was 9.6 years old, with a mean follow-up time of 34 months. Mean preoperative MPTA, MAD, and JLCA were significantly improved at the time of frame removal as well as at final follow-up with no significant changes in correction between the time of frame removal and final follow-up. There was no difference in MPTA and MAD in patients treated with an Ilizarov frame versus a TSF. MPTA, MAD, and JLCA all significantly improved regardless of the underlying diagnosis (infantile vs. adolescent Blount disease) or history of prior surgical intervention. The most common complication was superficial pin-site infection. CONCLUSIONS: Both Iliazarov and TSF are viable treatment options for infantile and adolescent Blount disease, with the ability to significantly improve both the limb mechanical axis and the mechanical axis of the affected tibia. Correction can be attained regardless of whether patients have previously failed surgical intervention. LEVEL OF EVIDENCE: Level III-retrospective comparative study.


Assuntos
Doenças do Desenvolvimento Ósseo/cirurgia , Fixadores Externos , Técnica de Ilizarov , Deformidades Articulares Adquiridas/cirurgia , Osteocondrose/congênito , Tíbia/cirurgia , Adolescente , Adulto , Mau Alinhamento Ósseo/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Osteocondrose/cirurgia , Osteotomia/métodos , Estudos Retrospectivos , Adulto Jovem
20.
J Cell Biol ; 218(6): 1908-1927, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31010855

RESUMO

In the conserved autophagy pathway, autophagosomes (APs) engulf cellular components and deliver them to the lysosome for degradation. Before fusing with the lysosome, APs have to close via an unknown mechanism. We have previously shown that the endocytic Rab5-GTPase regulates AP closure. Therefore, we asked whether ESCRT, which catalyzes scission of vesicles into late endosomes, mediates the topologically similar process of AP sealing. Here, we show that depletion of representative subunits from all ESCRT complexes causes late autophagy defects and accumulation of APs. Focusing on two subunits, we show that Snf7 and the Vps4 ATPase localize to APs and their depletion results in accumulation of open APs. Moreover, Snf7 and Vps4 proteins complement their corresponding mutant defects in vivo and in vitro. Finally, a Rab5-controlled Atg17-Snf7 interaction is important for Snf7 localization to APs. Thus, we unravel a mechanism in which a Rab5-dependent Atg17-Snf7 interaction leads to recruitment of ESCRT to open APs where ESCRT catalyzes AP closure.

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