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1.
Chemosphere ; 247: 125851, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31931315

RESUMO

Elemental defense hypothesis states that metals accumulated in plant tissues may serve as defense against herbivores and pathogens. However, evidences collected so far are inconsistent and studies using woody plants as model species are still lacking. In this study we used a local woody plant species, Populus yunnanensis, to investigate whether cadmium (Cd) accumulation in leaves can protect plants from leaf herbivory and pathogen infection. Plants grown with or without Cd supplementation in the soil were subjected to herbivory by a specialist (Botyodes diniasalis) and a generalist (Spodoptera exigua), or to pathogen infection by a leaf pathogenic fungus (Pestalotiopsis microspora). Two additional tests with artificial media amended with a series of Cd concentrations were conducted for S. exigua and P. microspora to investigate the toxicity of Cd independently of other organic defenses present in P. yunnanensis leaves. The results showed that both herbivores strongly preferred control leaves over leaves containing high Cd. Feeding on leaves from Cd-treated plants significantly reduced the growth and survivals of both herbivores. Furthermore, plants grown on Cd-amended soil were more resistant to fungal infection. Growth of S. exigua and P. microspora on artificial media decreased with increasing Cd concentrations. In conclusion, we found that Cd accumulated in P. yunnanensis leaves could effectively reduce leaf herbivory and pathogen infection, which fully supported the Elemental defense hypothesis.

2.
Neuroimage Clin ; 25: 102160, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31954337

RESUMO

BACKGROUND: The trigeminal nerve (TGN) is the largest cranial nerve and can be involved in multiple inflammatory, compressive, ischemic or other pathologies. Currently, imaging-based approaches to identify the TGN mostly rely on T2-weighted magnetic resonance imaging (MRI), which provides localization of the cisternal portion of the TGN where the contrast between nerve and cerebrospinal fluid (CSF) is high enough to allow differentiation. The course of the TGN within the brainstem as well as anterior to the cisternal portion, however, is more difficult to display on traditional imaging sequences. An advanced imaging technique, diffusion MRI (dMRI), enables tracking of the trajectory of TGN fibers and has the potential to visualize anatomical regions of the TGN not seen on T2-weighted imaging. This may allow a more comprehensive assessment of the nerve in the context of pathology. To date, most work in TGN tracking has used clinical dMRI acquisitions with a b-value of 1000 s/mm2 and conventional diffusion tensor MRI (DTI) tractography methods. Though higher b-value acquisitions and multi-tensor tractography methods are known to be beneficial for tracking brain white matter fiber tracts, there have been no studies conducted to evaluate the performance of these advanced approaches on nerve tracking of the TGN, in particular on tracking different anatomical regions of the TGN. OBJECTIVE: We compare TGN tracking performance using dMRI data with different b-values, in combination with both single- and multi-tensor tractography methods. Our goal is to assess the advantages and limitations of these different strategies for identifying the anatomical regions of the TGN. METHODS: We proposed seven anatomical rating criteria including true and false positive structures, and we performed an expert rating study of over 1000 TGN visualizations, as follows. We tracked the TGN using high-quality dMRI data from 100 healthy adult subjects from the Human Connectome Project (HCP). TGN tracking performance was compared across dMRI acquisitions with b = 1000 s/mm2, b = 2000 s/mm2 and b = 3000 s/mm2, using single-tensor (1T) and two-tensor (2T) unscented Kalman filter (UKF) tractography. This resulted in a total of six tracking strategies. The TGN was identified using an anatomical region-of-interest (ROI) selection approach. First, in a subset of the dataset we identified ROIs that provided good TGN tracking performance across all tracking strategies. Using these ROIs, the TGN was then tracked in all subjects using the six tracking strategies. An expert rater (GX) visually assessed and scored each TGN based on seven anatomical judgment criteria. These criteria included the presence of multiple expected anatomical segments of the TGN (true positive structures), specifically branch-like structures, cisternal portion, mesencephalic trigeminal tract, and spinal cord tract of the TGN. False positive criteria included the presence of any fibers entering the temporal lobe, the inferior cerebellar peduncle, or the middle cerebellar peduncle. Expert rating scores were analyzed to compare TGN tracking performance across the six tracking strategies. Intra- and inter-rater validation was performed to assess the reliability of the expert TGN rating result. RESULTS: The TGN was selected using two anatomical ROIs (Meckel's Cave and cisternal portion of the TGN). The two-tensor tractography method had significantly better performance on identifying true positive structures, while generating more false positive streamlines in comparison to the single-tensor tractography method. TGN tracking performance was significantly different across the three b-values for almost all structures studied. Tracking performance was reported in terms of the percentage of subjects achieving each anatomical rating criterion. Tracking of the cisternal portion and branching structure of the TGN was generally successful, with the highest performance of over 98% using two-tensor tractography and b = 1000 or b = 2000. However, tracking the smaller mesencephalic and spinal cord tracts of the TGN was quite challenging (highest performance of 37.5% and 57.07%, using two-tensor tractography with b = 1000 and b = 2000, respectively). False positive connections to the temporal lobe (over 38% of subjects for all strategies) and cerebellar peduncles (100% of subjects for all strategies) were prevalent. High joint probability of agreement was obtained in the inter-rater (on average 83%) and intra-rater validation (on average 90%), showing a highly reliable expert rating result. CONCLUSIONS: Overall, the results of the study suggest that researchers and clinicians may benefit from tailoring their acquisition and tracking methodology to the specific anatomical portion of the TGN that is of the greatest interest. For example, tracking of branching structures and TGN-T2 overlap can be best achieved with a two-tensor model and an acquisition using b = 1000 or b = 2000. In general, b = 1000 and b = 2000 acquisitions provided the best-rated tracking results. Further research is needed to improve both sensitivity and specificity of the depiction of the TGN anatomy using dMRI.

3.
Sensors (Basel) ; 20(1)2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31948012

RESUMO

Global navigation satellite system (GNSS)/inertial navigation system (INS) navigation technology is one of the core technologies in a mobile measurement system and can provide real-time geo-referenced information. However, in the environment measurements, buildings cover up the GNSS signal, causing satellite signals to experience loss-of-lock. At this time errors of INS independent navigation accumulate rapidly, so it cannot meet the needs of the mobile measurement system. In this paper, a positioning error compensation method based on plane control is proposed by analyzing the error characteristics of position and orientation caused by satellite signal loss-of-lock in the urban environment. This method control uses planar features and the laser point cloud positioning equation to establish an adjustment model that ignores the influence of the attitude error and finds the positioning error at the middle point of the GNSS signal loss-of-lock time period, and then compensates for the error at other points by using the characteristics of the positioning error. The experimental results show that the accuracy of the compensated laser point cloud has been significantly improved, and the feasibility of the method is verified. Meanwhile, the method can rely on the existing building plane so the method is adaptable and easy to implement.

4.
Int J Biol Macromol ; 146: 171-178, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31904457

RESUMO

Pickering high internal phase emulsions (HIPEs) stabilized solely by bioderived starch-based particles hold potential for application in the food and pharmaceutical fields. This paper reports the use of a thermoresponsive 2-hydroxy-3-butoxypropyl starch (HBPS) particle as a representative natural biocompatible material for use as an effective stabilizer for HIPE formation. HBPS is synthesized by using butyl glycidyl ether as a hydrophobic reagent to change the hydrophobic-hydrophilic balance of starch, and then starch-based particles are fabricated by a simple nanoprecipitation procedure. The size of particles increased with an increase in temperature, and the particles are essentially monodisperse with a PDI of about 0.1 when the temperature was above 15 °C. These HBPS particles were subsequently used as an effective stabilizer to fabricate stable oil-in-water (o/w) Pickering HIPEs with an internal phase volume of 80% at different stabilizer concentrations. The results demonstrated that increasing the particle concentration is conducive to the formation of stable Pickering HIPEs with greater stiffnesses. In addition, the nutraceutical material (ß-carotene) was encapsulated into HIPEs and in vitro release experiments revealed that the release in this system can be controlled by adjusting the temperature.

5.
Sensors (Basel) ; 20(2)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952172

RESUMO

Electronic healthcare (eHealth) identity management (IdM) is a pivotal feature in the eHealth system. Distributed ledger technology (DLT) is an emerging technology that can achieve agreements of transactional data states in a decentralized way. Building identity management systems using Blockchain can enable patients to fully control their own identity and provide increased confidence in data immutability and availability. This paper presents the state of the art of decentralized identity management using Blockchain and highlights the possible opportunities for adopting the decentralized identity management approaches for future health identity systems. First, we summarize eHealth identity management scenarios. Furthermore, we investigate the existing decentralized identity management solutions and present decentralized identity models. In addition, we discuss the current decentralized identity projects and identify new challenges based on the existing solutions and the limitations when applying it to healthcare as a particular use case.

6.
Int J Pharm ; : 119035, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31953080

RESUMO

Rebaudioside A (RA) self-assembled into ultrasmall nanomicelles can be utilized as ocular drug delivery system; nevertheless, the therapeutic efficacy of RA micelles has not evaluated thus far. In this manuscript, the RA micelles are thought to strengthen the therapeutic effects of pterostilbene (Pt). Results showed that Pt can be highly encapsulated into RA micelles with ultrasmall particle sizes (3.99 ± 0.03 nm) with a uniform distribution (polydispersity index, PDI = 0.184 ± 0.008). RA-Pt exhibited pronounced improvement for the in vitro antioxidant activity and the in vitro membrane permeation of Pt. RA-Pt exhibited good ocular tolerance. The use of RA-Pt led to the significant improvement in the in vivo intraocular permeation of Pt as well as the improvement in the in vivo anti-inflammatory efficacy. The in vivo evaluation of antioxidant effects revealed that RA-Pt exhibits improvement in suppressing the generation of oxidative stress and inducing the enzymes of reactive oxygen species (ROS) degradation. Furthermore, RA-Pt was confirmed to exhibit a strong treatment efficiency for corneal alkali burns. These findings indicate that RA-based self-assembled ultrasmall nanomicelles demonstrate tremendous potential toward the improvement in the ocular bioavailability as well as a therapeutic effect of poor aqueous soluble drugs such as Pt.

7.
Endocrine ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919771

RESUMO

PURPOSE: To find the sonographic features of follicular variant of papillary thyroid carcinoma (FV-PTC) and evaluate the diagnostic performance of 2017 ACR TI-RADS in FV-PTC. METHODS: From June 2017 to June 2019, 104 FV-PTC patients (106 nodules) and 337 classic papillary thyroid carcinoma (C-PTC) patients (343 nodules) with both sonograms and pathologic results were included. Sonographic features of FV-PTC and C-PTC were evaluated and compared, and 2017 ACR TI-RADS scores and levels were calculated. RESULTS: Pathologically, the incidence of Hashimoto's thyroiditis and extrathyroidal extension was higher in the FV-PTC group. Most of both the FV-PTC and C-PTC groups were diagnosed as PTC or suspicious PTC by fine-needle aspiration biopsy (FNAB). FV-PTC tended to be isoechoic, while most nodules of C-PTC were hypoechoic or very hypoechoic. Compared with C-PTC, FV-PTC had lower percentages of a taller-than-wide shape (11.3% vs. 46.6%) and lobulated or irregular margin (33.0% vs. 61.8%), and a higher percentage of extrathyroidal extension (20.8% vs. 8.2%). FV-PTC featured macrocalcifications, whereas punctate echogenic foci were more frequently seen in the C-PTC group. Other characteristic US appearances of FV-PTC included uneven hypoechoic halo and peripheral vascularity. The mean TI-RADS score of FV-PTC cases was lower in the FV-PTC group, 11.3%, 44.3%, and 42.5% of which were categorized as TI-RADS 3, 4, and 5, respectively. CONCLUSIONS: FV-PTC features isoechoic appearance, macrocalcifications, uneven hypoechoic halo, and peripheral vascularity on US, with lower incidences of microcalcifications and taller-than-wide shape, and tends to have lower TI-RADS scores and levels. For the nodules categorized as TI-RADS 3 or 4, the FNAB criteria should be broaden when these nodules have FV-PTC US features.

8.
Mikrochim Acta ; 187(2): 101, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912240

RESUMO

A freestanding and flexible buckypaper modfied with CoP/Co (CoP/Co-BP) is described. It has a sponge-like nanostructure and is shown to enable improved nonenzymatic sensing of glucose. The CoP/Co-BP was prepared by first depositing a uniform layer of ZIF- 67 crystals on BP, followed by two steps of pyrolysis treatment and phosphidation under an argon atmosphere. The morphology and structure of the material were characterized by scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The electrochemical properties were investigated by cyclic voltammetry and amperometric response. The amperometric sensor, best operated at 0.45 V (vs. SCE) at pH 13 has a linear range that extends from 0.5 µM to 1.8 mM of glucose, a 0.2 µM detection limit (at S/N = 3), and a sensitivity of 6427 µA mM-1 cm-2 in alkaline solution. This is mainly attributed to the synergistic effect between the highly active CoP nanostructure and BP which results in excellent conductivity. The uniformly distributed CoP nanoparticles in the network of BP prevent the formation of close-packed structure and facilitate electron transfer. The sensor has good selectivity and excellent long-term stability. It was applied to the determination of glucose in spiked human serum, and satisfactory results were obtained. Graphical abstractSchematic presentation of a freestanding and flexible buckypaper modfied with CoP/Co. It has a sponge-like nanostructure and exhibits improved catalytic activity toward glucose oxidation. This material was used for high-performance electrochemical glucose sensing.

9.
Medicine (Baltimore) ; 99(1): e18576, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895804

RESUMO

A substantial limitation of dialysis fistulas is their high primary failure rate due to nonmaturation. Various studies have documented that patients with larger vein diameters exhibit reduced risks for nonmaturation. Nevertheless, some patients have small veins. Few studies have focused on patients with small veins. We hypothesize that sufficient venous dilation contributes to fistula maturation. Therefore, we studied the influence of cephalic vein dilation on fistula maturation in patients with small veins.Patients with small cephalic veins (diameter <2 mm) undergoing initial arteriovenous fistulae (AVF) operation were included. A total of 72 patients were enrolled in this study. A prospective study was performed, and the patients were followed for 6 weeks after surgery. Preoperative and postoperative duplex ultrasound mapping of veins was performed, and dilation of the cephalic vein was evaluated.The fistula maturation rate was 44.44%. Multivariate logistic regression analysis revealed a significant relationship between fistula maturation and preoperative cephalic vein dilation. Based on the results of ROC analysis, the fistula maturation rate in patients with vein dilation greater than or equal to the cut-off was 57.14% in the training data set and 54.55% in the testing data set. The independent influencing factors for fistula maturation were used to establish a combined index with logistic regression analysis. The fistula maturation rate in patients with combined indexes greater than or equal to the cut-off was 80.95% in the training data set and 77.78% in the testing data set.Our results demonstrated that preoperative venous dilation was associated with AVF maturation. For patients with small veins, venous distensibility needs to be carefully assessed before surgery, as it may be a better predictor of AVF maturation than venous diameter.


Assuntos
Braço/irrigação sanguínea , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Adulto , Idoso , Braço/diagnóstico por imagem , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Diálise Renal , Ultrassonografia
10.
J Matern Fetal Neonatal Med ; : 1-9, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31902261

RESUMO

Background: Due to physiological and hormonal factors, sleep disturbances are prevalent in the obstetric population. Multiple studies have evaluated the relationship between sleep disturbances and perinatal outcomes, with inconsistent results. The purpose of this systematic review and meta-analysis was to further assess the overall relationship between four types of sleep disturbances (snoring, obstructive sleep apnea, extreme sleep duration, and poor sleep quality) and adverse perinatal outcomes.Methods: We performed electronic searches in PubMed, Embase, the Cochrane Library, CNKI, VIP, and Wanfang Data in February 2019 to identify studies that assessed adverse perinatal outcomes among expectant mothers with sleep disturbances.Results: In total, 5044 studies were identified in the initial search and 65 met the defined criteria. Pooled analysis showed that sleep disturbances were associated with an increased risk for preeclampsia (aOR: 2.77; 95% CI: 1.81-4.24), gestational diabetes mellitus (aOR: 1.96; 95% CI: 1.62-2.38), cesarean delivery (aOR: 1.99; 95% CI: 1.70-2.33), depression (aOR: 3.98; 95% CI: 2.74-5.77) and preterm birth (aOR: 1.95; 95% CI: 1.55-2.45).Conclusions: The four studied sleep disturbances (OSA, snoring, extreme sleep duration and poor sleep quality) during pregnancy were associated with adverse perinatal outcomes. Expectant mothers should be advised to practice healthy sleep hygiene measures.

11.
Sci Prog ; : 36850419881896, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31893978

RESUMO

Parallel kinematic machines have been applied in aerospace and automotive manufacturing due to their potentials in high speed and high accuracy. However, there exists coupling in parallel kinematic machines, which makes dynamic analysis, rigidity enhancement, and control very complicated. In this article, coupling characteristics of a 5-degree-of-freedom (5-dof) hybrid manipulator are analyzed based on a local index and a global index. First, velocity analysis as well as acceleration analysis of the robot is conducted to provide essential information for dynamic modeling. Then the dynamic model is built based on the principle of virtual work. Whereas the mass matrix is off-diagonal, a local coupling index as well as a global index is defined, based on which coupling characteristics of the robot are analyzed. Results show that distributions of coupling indices are symmetric due to its structural features. And dimensional parameters, structural parameters, as well as mass parameters have a large influence on the system's coupling characteristics. Research conducted in the article is of great help in optimal design and control. Meanwhile, the method proposed in the article can be applied to other types of parallel kinematic machines or hybrid manipulators.

12.
Mol Pharm ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910019

RESUMO

Biomedical nanoplatforms have been widely investigated for ultrasound imaging and cancer therapy. Herein, a theranostic nanosystem is developed using biocompatible polydopamine (PDA) to encapsulate perflurocarbon (PFC) and polyethylene glycol (PEG) to stabilize the nanoparticle via a facile one-pot method. PDA exhibits high photothermal conversion efficiency under near-infrared (NIR) laser irradiation at 808 nm, generating hyperthermia to transform the perfluorocarbon droplets to bubbles with high ultrasound imaging sensitivity. The ultrasound (US) imaging detection of PFC-PDA-PEG nanosystem is achievable at a time span up to 25 min in vitro at low US frequency and mechanical index, manifesting an US imaging performance to allow application in vivo. Moreover, tumor cells incubated with the nanosystem are ablated effectively under laser irradiation at 808 nm. The results illustrate the potential of the PDA-based theranostic agent in US imaging-guided photothermal therapy of tumor.

13.
J Bone Miner Res ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910300

RESUMO

X-linked hypophosphatemia (XLH), the most prevalent heritable renal phosphate (Pi) wasting disorder, is caused by deactivating mutations of PHEX. Consequently, circulating phosphatonin FGF23 becomes elevated and hypophosphatemia in affected children leads to rickets with skeletal deformity and reduced linear growth while affected adults suffer from osteomalacia and forms of ectopic mineralization. In 2015, we reported uniquely mild XLH in six children and four of their mothers carrying the non-coding PHEX 3'-UTR mutation c.*231A>G. Herein, we characterize this mild XLH variant by comparing its features in 30 individuals to 30 age- and sex-matched patients with XLH but without the 3'-UTR mutation. The "UTR" and "XLH" groups, both comprising 17 children (2-17 years, 3 girls) and 13 adults (23-63 years, 10 women), had mean ages of 23 years. Only 43% of the UTR group versus 90% of the XLH group had received medical treatment for their disorder, including 0% versus 85% of the females, respectively (ps< 0.0001). The UTR group was taller: mean (SD) height Z-score (HZ) -1.0 (1.0) versus -2.0 (1.4) (p=0.0034), with significantly greater height for females [-0.9 (0.7) versus -2.3 (1.4), (p=0.0050)] but not males [-1.2 (1.1) versus -1.9 (1.5) (p=0.1541)], respectively. Mean (SD) "arm span Z-score" (AZ) did not differ between the UTR -0.8 (1.3) versus XLH -1.3 (1.8) groups (p=0.2269). Consequently, the UTR group was more proportionate with a mean ∆Z (AZ - HZ) of 0.1 (0.6) versus 0.7 (1.0) (p=0.0158), respectively. Compared to the XLH group, the UTR group had significantly higher fasting serum Pi and TmP/GFR (ps≤0.0060), serum FGF23 concentrations within the reference range (p=0.0068), and similar serum alkaline phosphatase levels (p = 0.6513). UTR lumbar spine bone mineral density Z-score was higher (p=0.0343). Thus, the 3'-UTR variant of XLH is distinctly mild, especially in girls and women, posing challenges for its recognition and management. This article is protected by copyright. All rights reserved.

14.
Anal Chim Acta ; 1097: 245-253, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-31910966

RESUMO

In this work, we based on an iminocoumarin borate complex to design and synthesize a red-emitting fluorescent probe, THQ-BF2-O-NBD, to discriminatively detect Cys/Hcy and GSH with a large Stokes shift (100 nm). This probe responded to GSH to display red fluorescence with λmax = 630 nm. In contrast, two well-separated emission bands with λmax = 565 and 630 nm were observed in the solution of THQ-BF2-O-NBD with Cys/Hcy. The probe was capable to distinguish Cys/Hcy from GSH in real biological systems.

15.
Exp Mol Pathol ; 113: 104375, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31917288

RESUMO

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes mellitus.The main pathological features of DN include glomerular sclerosis and renal tubular interstitial fibrosis, which results in epithelial mesenchymal transition (EMT) and excessive extracellular matrix (ECM) deposition.Transforming growth factor-ß1(TGF-ß1) is a critical factor that regulates the manifestation of renal fibrosis.Smad2 and Smad3 are the main downstream of the TGF-ß1 pathway. Ski-related novel protein N(SnoN) is a negative regulator of TGF-ß1, and inhibits the activation of the TGF-ß1/Smad2/3 signalling pathway. In this study, the expression of Smad2 and Smad3 proteins, SnoN mRNA, SnoN proteins, and the ubiquitination levels of SnoN were determined in DN rats and renal tubular epithelial cells(NRK52E cells). Knockdown and overexpression of Smad2 or Smad3 in NRK52E cells were used to investigate the specific roles of Smad2 and Smad3 in the development of high glucose-induced renal tubular fibrosis, with a specific focus on their effect on the regulation of SnoN expression. Our study demonstrated that Smad3 could inhibit SnoN expression and increase ECM deposition in NRK52E cells, to promote high glucose-induced renal tubular fibrosis. In contrast, Smad2 could induce SnoN expression and reduce ECM deposition, to inhibit high glucose-induced fibrosis. The underlying mechanism involves regulation of SnoN expression. These findings provide a novel mechanism to understanding the significant role of the TGF-ß1/ Smad2/3 pathway in DN.

16.
Theranostics ; 10(3): 1197-1212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31938060

RESUMO

Objective: Vascular smooth muscle cells (VSMCs) undergo the phenotypic changes from contractile to synthetic state during vascular remodeling after ischemia. SIRT1 protects against stress-induced vascular remodeling via maintaining VSMC differentiated phenotype. However, the effect of smooth muscle SIRT1 on the functions of endothelial cells (ECs) has not been well clarified. Here, we explored the role of smooth muscle SIRT1 in endothelial angiogenesis after ischemia and the underlying mechanisms. Methods: We performed a femoral artery ligation model using VSMC specific human SIRT1 transgenic (SIRT1-Tg) and knockout (KO) mice. Angiogenesis was assessed in in vivo by quantification of the total number of capillaries, wound healing and matrigel plug assays, and in vitro ECs by tube formation, proliferation and migration assays. The interaction of HIF1α with circRNA was examined by using RNA immunoprecipitation, RNA pull-down and in situ hybridization assays. Results: The blood flow recovery was significantly attenuated in SIRT1-Tg mice, and markedly improved in SIRT1-Tg mice treated with SIRT1 inhibitor EX527 and in SIRT1-KO mice. The density of capillaries significantly decreased in the ischemic gastrocnemius of SIRT1-Tg mice compared with SIRT1-KO and WT mice, with reduced expression of VEGFA, which resulted in decreased number of arterioles. We identified that the phenotypic switching of SIRT1-Tg VSMCs was attenuated in response to hypoxia, with high levels of contractile proteins and reduced expression of the synthetic markers and NG2, compared with SIRT1-KO and WT VSMCs. Mechanistically, SIRT1-Tg VSMCs inhibited endothelial angiogenic activity induced by hypoxia via the exosome cZFP609. The cZFP609 was delivered into ECs, and detained HIF1α in the cytoplasm via its interaction with HIF1α, thereby inhibiting VEGFA expression and endothelial angiogenic functions. Meantime, the high cZFP609 expression was observed in the plasma of the patients with atherosclerotic or diabetic lower extremity peripheral artery disease, associated with reduced ankle-brachial index. Knockdown of cZFP609 improved blood flow recovery after hindlimb ischemia in SIRT1-Tg mice. Conclusions: Our findings demonstrate that SIRT1 may impair the plasticity of VSMCs. cZFP609 mediates VSMCs to reprogram endothelial functions, and serves as a valuable indicator to assess the prognosis and clinical outcomes of ischemic diseases.

17.
Emerg Microbes Infect ; 9(1): 111-123, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31906823

RESUMO

The Zika virus (ZIKV) is a mosquito-borne flavivirus that causes neonatal abnormalities and other disorders. Antibodies to the ZIKV envelope (E) protein can block infection. In this study, next-generation sequencing (NGS) of immunoglobulin heavy chain (IgH) mRNA transcripts was combined with single-cell PCR cloning of E-binding monoclonal antibodies for analysing antibody response in a patient from the early stages of infection to more than one year after the clearance of the virus. The patient's IgH repertoire 14 and 64 days after symptom onset showed dramatic dominant clonal expansion but low clonal diversity. IgH repertoire 6 months after disease-free status had few dominant clones but increased diversity. E-binding antibodies appeared abundantly in the repertoire during the early stages of infection but quickly declined after clearance of the virus. Certain VH genes such as VH5-10-1 and VH4-39 appeared to be preferentially enlisted for a rapid antibody response to ZIKV infection. Most of these antibodies require relatively few somatic hypermutations to acquire the ability to bind to the E protein, pointing to a possible mechanism for rapid defence against ZIKV infection. This study provides a unique and holistic view of the dynamic changes and characteristics of the antibody response to ZIKV infection.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31891251

RESUMO

A porous polyimide (PI) membrane is successfully prepared via nonsolvent-induced phase separation with two porogens: dibutyl phthalate and glycerin. The as-prepared uniform porous PI membrane shows excellent separator properties for lithium-ion batteries (LIBs). Compared with the commercial polyethylene (PE) separator, the PI separator exhibits significant thermal stability, better ionic conductivity, and wettability both in carbonate and ether electrolytes for LIBs. The battery coin-cells assembled with the PI separator is more robust and still works even after heating at 140 °C for 1 h, while the cells with the commercial PE separator could not charge any more due to the shrinkage of the PE under the same condition.

19.
Cancer Res ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911551

RESUMO

53BP1 controls two downstream sub-pathways, one mediated by PTIP and Artemis and the other by RIF1 and MAD2L2/Shieldin, to coordinate DNA repair pathway choices. However, the upstream regulator(s) of 53BP1 function in DNA repair remain unknown. We and others recently reported that TIRR associates with 53BP1 to stabilize it and prevents 53BP1 localization to DNA damage sites by blocking 53BP1 Tudor domain binding to H4K20me2 sites. Here, we report that the Nudix hydrolase NUDT16, a TIRR homolog, regulates 53BP1 stability. We identified a novel post-translational modification of 53BP1 by ADP-ribosylation that is targeted by a PAR-binding E3 ubiquitin ligase, RNF146, leading to 53BP1 polyubiquitination and degradation. In response to DNA damage, ADP-ribosylated 53BP1 increased significantly, resulting in its ubiquitination and degradation. These data suggest that NUDT16 plays a major role in controlling 53BP1 levels under both normal growth conditions and during DNA damage. Notably, overexpression of a NUDT16 catalytically inactive mutant blocked 53BP1 localization to double-strand breaks because: 1) the mutant binding to TIRR increased after IR; 2) the mutant enhanced 53BP1 Tudor domain binding to TIRR, and 3) the mutant impaired the interaction of 53BP1 Tudor domain with H4K20me2. Moreover, NUDT16's catalytic hydrolase activity was required for 53BP1 de-ADP-ribosylation, 53BP1 protein stability, and its function in cell survival. In summary, we demonstrate that NUDT16 regulates 53BP1 stability and 53BP1 recruitment at double-strand breaks, providing yet another mechanism of 53BP1 regulation.

20.
FASEB J ; 34(1): 555-570, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914652

RESUMO

Muscle wasting, or muscle atrophy, can occur with age, injury, and disease; it affects the quality of life and complicates treatment. Insulin-like growth factor 1 (IGF1) is a key positive regulator of muscle mass. The IGF1/Igf1 gene encodes multiple protein isoforms that differ in tissue expression, potency, and function, particularly in cellular proliferation and differentiation, as well as in systemic versus localized signaling. Genome engineering is a novel strategy for increasing gene expression and has the potential to recapitulate the diverse biology seen in IGF1 signaling through the overexpression of multiple IGF1 isoforms. Using a CRISPR-Cas9 gene activation approach, we showed that the expression of multiple IGF1 or Igf1 mRNA variants can be increased in human and mouse skeletal muscle myoblast cell lines using a single-guide RNA (sgRNA). We found increased IGF1 protein levels in the cell culture media and increased cellular phosphorylation of AKT1, the main effector of IGF1 signaling. We also showed that the expression of Class 1 or Class 2 mRNA variants can be selectively increased by changing the sgRNA target location. The expression of multiple IGF1 or Igf1 mRNA transcript variants in human and mouse skeletal muscle myoblasts promoted myotube differentiation and prevented dexamethasone-induced atrophy in myotubes in vitro. Our findings suggest that this novel approach for enhancing IGF1 signaling has potential therapeutic applications for treating skeletal muscle atrophy.

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