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1.
Biosci Rep ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030503

RESUMO

Bone morphogenetic protein-2 (BMP-2) is commonly applied in spinal surgery to augment spinal fusion. Nevertheless, its pro-inflammatory potential could induce dangerous side effects such as vascular hyper-permeability, posing the need for manners against this condition. This study aims to investigate the protective effect of Zanthoxylum nitidum (ZN) on BMP-2 related hyperpermeability and inflammation on the human umbilical vein endothelial cells (HUVECs). The results revealed that, in a concentration-dependent manner, BMP-2 enhanced the production of pro-inflammatory cytokines, including interleukin (IL)-1α, IL-1ß, and tumor necrosis factor-α, which were, however, suppressed by ZN. ZN inhibited BMP-2-induced inflammatory response by suppressing the phosphorylation of NF-κBp65 and IκB, and the abnormal nuclear translocation of p65. Moreover, the inhibited expression intercellular tight junction protein VE-cadherin and Occludin caused by BMP-2 was blocked by ZN. The hyper-permeability of HUVECs induced by BMP-2, as expressed as the higher fluorescent intensity of dextran, was also reversed by ZN. Overall, these findings demonstrated that ZN antagonized BMP2-induced inflammation and hyperpermeability. It could be a therapeutic candidate for the treatment of BMP-2-induced side effects during spinal fusion.

2.
Genet Mol Biol ; 43(4): e20190392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33026411

RESUMO

Coraciiformes contains more than 200 species with great differences on external morphology and life-style. The evolutionary relationships within Coraciiformes and the phylogenetic placement of Coraciiformes in Aves are still questioned. Mitochondrial genome (mitogenome) sequences are popular markers in molecular phylogenetic studies of birds. This study presented the genome characteristics of three new mitogenomes in Coraciiformes and explored the phylogenetic relationships among Coraciiformes and other five related orders with mitogenome data of 30 species. The sizes of three mitogenomes were 17,383 bp (Alcedo atthis), 17,892 bp (Halcyon smyrnensis) and 17,223 bp (Megaceryle lugubris). Each mitogenome contained one control region and 37 genes that were common in vertebrate mitogenomes. The organization of three mitogenomes was identical to the putative ancestral gene order in Aves. Among 13 available Coraciiform mitogenomes, 12 protein coding genes showed indications of negative selection, while the MT-ND6 presented sign of positive selection or relaxed purifying selection. The phylogenetic results supported that Upupidae and Bucerotidae should be separated from Coraciiformes, and that Coraciiformes is more closely related to Piciformes than to Strigiformes, Trogoniformes and Cuculiformes. Our study provide valuable data for further phylogenetic investigation of Coraciiformes.

3.
Bioconjug Chem ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001643

RESUMO

Development of nanoplatforms for targeted anticancer drug delivery for effective tumor therapy still remains challenging in the development of nanomedicine. Here, we present a facile method to formulate a LAPONITE (LAP) nanodisk-based nanosystem for anticancer drug doxorubicin (DOX) delivery to folic acid (FA) receptor-overexpressing tumors. In the current work, aminated LAP nanodisks were first prepared through silanization, then functionalized with polyethylene glycol-linked FA (PEG-FA) via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemistry, and finally employed to physically encapsulate DOX. The formed functional LAP nanodisks (for short, LM-PEG-FA) possess a high DOX loading efficiency (88.6 ± 1.2%) and present a pH-dependent release feature with a quicker DOX release under acidic pH conditions (pH 5.0) than under physiological pH conditions (pH 7.4). In vitro flow cytometry, confocal microscopic observation, and cell viability assay show that the LM-PEG-FA/DOX complexes can be specifically taken up by FAR-overexpressing human ovarian cancer cells (SK-OV-3 cells) and present a specific cancer cell therapeutic effect. Further tumor treatment results reveal that the LM-PEG-FA/DOX complexes can exert a specific therapeutic efficacy to a xenografted SK-OV-3 tumor model in vivo when compared with nontargeted LM-mPEG/DOX complexes. Therefore, the developed LM-PEG-FA nanodisks could be employed as a potential platform for targeted cancer chemotherapy.

4.
Neurol Sci ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037513

RESUMO

PURPOSE: Early recanalization for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) by endovascular thrombectomy (EVT) is strongly related to improved functional outcomes. With data obtained from the Taiwan registry, the factors associated with mTICI 3 recanalization and clinical outcomes in EVT are investigated. METHODS: From January 2014 to September 2016, 108 patients who underwent EVT for AIS due to LVO in 11 medical centers throughout Taiwan were included. Complete recanalization is defined as achieving modified thrombolysis in cerebral infarction (mTICI) grade 3. Good clinical outcomes are defined by the modified Rankin scale (mRS) 0-2 at 3 months after EVT. Clinical and imaging parameters for predicting mTICI 3 recanalization and good clinical outcomes are analyzed. RESULTS: Of the 108 patients who received EVT, 54 (50%) patients had mTICI 3 recanalization. Having received aspiration only and the use of IV-tPA are shown to be significant predictors for mTICI 3 recanalization with odds ratios of 2.61 and 2.53 respectively. Forty-six (42.6%) patients experienced good 3-month clinical outcomes (mRS 0-2). Pretreatment collateral statuses, NIHSS scores, time lapses between symptoms to needle, and the occurrence of hemorrhage at 24 h are all significant predictors for good outcomes with odds ratios of 2.88, 0.91, 0.99, and 0.31 respectively. CONCLUSIONS: Prediction of mTICI 3 recanalization and clinical outcomes offer valuable clinical information for treatment planning in EVT.

5.
Cancer Invest ; : 1-17, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32998588

RESUMO

To evaluate prognosis of breast cancer patients, a total of 16618 TNBC patients from SEER database were involved. High grade, unmarried status, tumor site were the main factors reduced OS in stage I. Black race, unmarried, large tumor size, and nodes metastasis would make worse prognosis in stage II. Compared with stage II, race and marital status had no significant effect on the prognosis in stage III. In stage IV, married status significantly improved the OS and DSS. Surgery and chemotherapy improve survival time in all of stages. Clinicopathological status correlated with the prognosis of patients with differentially staged TNBC.

6.
Biol Pharm Bull ; 43(10): 1481-1489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32999158

RESUMO

Stroke is a common cerebrovascular disease. Inflammation-induced neuronal death is one of the key factors in stroke pathology. Propofol has been shown to ameliorate neuroinflammatory injury, but the exact mechanism of its neuroprotective role remains to be fully elucidated. In the present study, we found that inflammation was activated in ischemic cortical neurons, and the expression of nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 1 (NLRP1), NLRP3 inflammasome and effectors in primary cortical neurons increased. However, we found that propofol could inhibit the increased expression of NLRP1 and NLRP3 inflammasome induced by oxygen-glucose deprivation (OGD). Furthermore, the effector molecule caspase-1 (casp1) was revealed to be the downstream target of NLRP1 and propofol repressed the activation of caspase-1 via inhibiting NLRP1 in cortical neurons. Moreover, propofol inhibits caspase-6 activation in neurons through the NLRP1-caspase-1 pathway. Once the expression of caspase6 increases, propofol reduced its neuroprotective effect in OGD-treated cortical neurons. In the stroke middle cerebral artery occlusion (MCAO) model, infusion of caspase-6 inhibitors enhanced the protective effect of propofol on infarct size and neurological function. In conclusion, our results suggest that propofol plays a neuroprotective role in stroke by inhibiting the inflammatory pathway of NLRP1-caspase-1-caspase-6. Overall, these data suggest that propofol plays a key role in the inflammatory-dependent pathway after stroke, providing an important evidence for propofol as an effective strategy for neuroprotection in stroke.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32999465

RESUMO

BACKGROUND: To investigate the feasibility of a freehand transperineal (TP) systematic prostate biopsy protocol under local anaesthesia (LA) and the value of different sectors in diagnosing prostate cancer (PCa). METHODS: A total of 611 consecutive freehand TP biopsies under LA in 2 hospitals were prospectively evaluated. Cancer detection rate in each of the four different sectors (anterior, mid, posterior, basal) was recorded to evaluate the value of each sector. Procedure tolerability was assessed by pain score and complications were documented. RESULTS: Systematic biopsies were performed in 556 out of 611 men with a median of 20 (IQR 12-24) biopsy cores taken. The median PSA was 9.9 (Inter-quartile range[IQR] 6.4-16.2) ng/mL, and 89.0% were first biopsies. All PCa and ISUP grade group (GG) ≥ 2 PCa (HGPCa) were diagnosed in 41.4% (230/556) and 28.2% (157/556) biopsies respectively. 77.0% HGPCa was diagnosed in ≥2 sectors. Single-sector HGPCa was predominantly found in anterior or posterior sector. Omitting base sector would have missed 1.5% (1/65) HGPCa out of the 219 cases with ≥24-core biopsies performed. Further omission of mid sector would have missed 3.1% (2/65) HGPCa and 7.4% (7/94) ISUP GG1 PCa (in which 3/7 involved 2 sectors). LA TP biopsy was well tolerated and the mean pain scores of the different steps of the procedure were between 1.9-3.1 (out of 10). Post-biopsy fever occurred in 0.3% of patients (2/611) and no sepsis was reported. The risk of urinary retention in men with ≥20 cores in ≥60 ml prostate was 7.8% (14/179), compared with 1.7% (7/423) in other groups (p < 0.001). CONCLUSIONS: TP sectoral prostate biopsy under LA was well tolerated with minimal sepsis risk. Basal sector biopsies had minimal additional value to HGPCa detection and its omission can be considered.

8.
J Hazard Mater ; 404(Pt A): 124145, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33032089

RESUMO

Three magnetic biochar nanocomposites named as C800-1, C800-2 and C800-3 with increased iron deposition amount, decreased graphitized degree and gradually destroyed graphitized carbon layers, respectively, were prepared using potassium ferrate as activator and corn straw as biomass. C800-1, C800-2 and C800-3 exhibited much different bisphenol A degradation effect in presence of peroxymonosulfate among which C800-3 owned the best catalytic performance. For the degradation mechanism, the dominant role of electron transfer pathway was gradually replaced by the SO4•- pathway with the increase of iron amount and the destruction of graphitized carbon layers. This work would provide a simple and feasible method, namely changing the ratio of potassium ferrate and biochar, to manipulate the radical and nonradical degradation pathway in PMS-based organic wastewater purification.

9.
Clin Rehabil ; : 269215520961637, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33040592

RESUMO

OBJECTIVE: This study aimed to investigate the efficacy of high-intensity functional exercise among older adults with dementia. METHODS: In this systematic review and meta-analysis of randomized controlled trials, we collected articles published before August 2020 from PubMed, Embase, and the Cochrane Library to evaluate the effect of high-intensity functional exercise on older adults with dementia. Primary outcomes included improvements in balance function and gait performance (speed, cadence, and stride length). The secondary outcomes included lower limb strength, activities of daily living, psychiatric well-being, depression, and cognition. Furthermore, we performed subgroup analysis with two high-intensity functional exercise programs: the Umeå program and Hauer's program. RESULTS: We identified 15 articles describing six trials including older adults with dementia undergoing high-intensity functional exercise or control activity. The meta-analysis indicated that high-intensity functional exercise, both in Hauer's program and in the Umeå program, significantly improved balance function (pooled standardized mean difference 0.57, 95% confidence interval 0.31-0.83). Hauer's program significantly improved gait speed, cadence, stride length, and lower limb strength. Beneficial effects on speed, cadence, and lower limb strength were retained for several months. The Umeå program facilitated activities of daily living and psychiatric well-being, with effects on activities of daily living lasting several months. In the only eligible trial, no effects on cognition were observed. Adverse effects of high-intensity functional exercise were minimal to none. CONCLUSIONS: High-intensity functional exercise is generally safe and is recommended for older individuals with mild or moderate dementia to provide benefits in motor performance and daily functioning.

10.
Biomaterials ; 264: 120365, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32971372

RESUMO

In the recent decades, fluorogens with aggregation-induced emission (AIEgens) have been intensively explored in biomedical applications. One main strategy to bring these hydrophobic AIEgens into the aqueous biological environment is to encapsulate them in nanoparticles with functionalized polymeric matrices. However, exploration of reliable strategies that can afford AIE nanoparticles with uniform size and stable loading efficiency with minimized variation still remains a challenge. Here, we rationally designed amphiphilic AIEgens, constructed by a hydrophobic donor-acceptor-donor (D-A-D) core and hydrophilic polyethylene glycol (PEG) chain. The afforded amphiphilic AIEgens can self-assemble into uniform nanoparticles with average sizes of ~35 nm, showing an emission maximum beyond 1000 nm and quantum yields (QYs) above 10%. We then used the bright AIE nanoparticles for multiscale intravital vascular fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) in mouse and rabbit models with a high-resolution of ~38 µm and a penetration depth of ~1 cm. As such, our results demonstrate an efficient self-assembly strategy to construct advanced AIE nanoparticles for angiography.

11.
Biomater Sci ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32996477

RESUMO

Intraosseous transcutaneous implants transferring mechanical stress directly from the skeleton to a prosthesis are an area of biological mechanics. However, bacterial invasion and weak biosealing with skin tissue usually induce implant failure. In this paper, composite coatings consisting of ß-FeOOH as an outer layer and Fe-TiO2 as an inner layer were prepared on Ti via micro-arc oxidation and hydrothermal treatment (HT). The surface microstructures and optical absorption properties of the coatings were observed, the production of reactive oxygen species (ROS) was measured, Staphylococcus aureus (S. aureus) and fibroblast behaviors were studied in vitro, and bacteria inactivation and skin tissue responses on different surfaces were evaluated in vivo. The results show that Fe3+ was doped into TiO2 and ß-FeOOH nanoparticles were gradually deposited on TiO2 during HT treatment, forming ß-FeOOH/Fe-TiO2 heterojunctions. The light absorption of the composite coatings shifted to the longer wavelength region because of a narrowed TiO2 bandgap and the formation of heterojunctions. Under light irradiation, photoinduced electrons and holes on the heterojunctions were separated efficiently. Via optimizing the amount of Fe3+ in TiO2, ROS that formed at the heterojunctions after light irradiation for 10 min could kill 80% of S. aureus compared with pure Ti in vitro, but they did not affect fibroblast behavior, including proliferation and phenotyping. In vivo, the optimized ß-FeOOH/Fe-TiO2 heterojunctions, upon light irradiation, could inhibit bacterial infection, suppress an inflammatory response, and promote integration with skin tissue. Such results provide a new perspective suggesting the potential application of ß-FeOOH/Fe-TiO2 heterojunctions in percutaneous Ti implants, especially in infected cases.

12.
J Vasc Interv Radiol ; 31(10): 1587-1591, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32951970

RESUMO

Intraductal cooling via a percutaneous transhepatic biliary drainage tube holds great promise in facilitating thermal ablation of liver tumors adjacent to the central bile ducts. However, the difficulties and complications associated with puncturing nondilated bile ducts are greater than those associated with puncturing dilated bile ducts. As reported here, percutaneous transcholecystic contrast-enhanced ultrasound was performed in 7 patients to visualize the nondilated bile ducts and guide percutaneous transhepatic biliary drainage, thus facilitating the intraductal cooling-assisted thermal ablation process. The procedures were technically successful in all 7 patients, and no major complications were recorded during the follow-up period.

13.
Sci Rep ; 10(1): 15731, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978441

RESUMO

Oviposition by Gasterophilus pecorum on shoot tips of Stipa caucasica is a key determinant of its severe infection of the reintroduced Przewalski's horse (Equus przewalskii). Volatiles in shoots of grasses on which Przewalski's horse feeds, including S. caucasica at preoviposition, oviposition, and postoviposition stages of G. pecorum, S. caucasica, Stipa orientalis, and Ceratoides latens at the oviposition stage, and S. caucasica in various growth periods, were collected by dynamic headspace adsorption and analyzed by automatic thermal desorption gas chromatography-mass spectrometry. Among five volatiles with highest relative contents under three sets of conditions, caprolactam and 3-hexen-1-ol,(Z)- were common to all samples. Caprolactam was highest in C. latens at oviposition stage of G. pecorum and lowest in S. caucasica at postoviposition stage, and that of 3-hexen-1-ol,(Z)- was lowest in C. latens and highest in S. caucasica at its oviposition stage. Particularly, in S. caucasica during the three oviposition phenological stages of G. pecorum, 3-hexen-1-ol,acetate,(Z)-, 2(5H)-furanone,5-ethyl-, and 3-hexen-1-ol,acetate,(E)- were unique, respectively, to the preoviposition, oviposition, and postoviposition stages; in three plant species during the oviposition stage of G. pecorum, 3-hexen-1-ol,acetate,(Z)-, 3-hexenal, and 1-hexanol were unique to S. orientalis, acetic acid, hexanal, and 2(5H)-furanone,5-ethyl- to S. caucasica, and 1,3,6-octatriene,3,7-dimethyl-, cis-3-hexenyl isovalerate, and acetic acid hexyl ester to C. latens; in S. caucasica, 2-undecanone,6,10-dimethyl- was unique to the early growth period, acetic acid and 2(5H)-furanone,5-ethyl- to the flourishing growth period, and 3-hexen-1-ol,acetate,(Z)- and 1,3,6-octatriene,3,7-dimethyl- to the late growth period. Furthermore, substances specific to S. orientalis and C. latens were also present in S. caucasica, except at oviposition stage. Our findings will facilitate studies on G. pecorum's adaptation to the arid desert steppe and its future control.

14.
Mikrochim Acta ; 187(10): 574, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32964251

RESUMO

A reliable electrochemical biosensor is reported based on nitrogen-doped graphene nanosheets and gold nanoparticle (Au/N-G) nanocomposites for the event-specific detection of GM maize MIR162. The differential pulse voltammetry response of methylene blue (MB) was chosen to monitor the target DNA hybridization event. Under the optimum conditions, the peak current increased linearly with the logarithm of the concentration of DNA in the range 1.0 × 10-14 to 1.0 × 10-8 M, and the detection limit was 2.52 × 10-15 M (S/N = 3). It is also demonstrated that the DNA biosensor has high selectivity, good stability, and fabrication reproducibility. The biosensor has been effectively applied to detect MIR162 in real samples, showing its potential as an effective tool for GM crop analysis. These results will contribute to the development of new portable transgenic detection systems. Graphical abstract .

15.
Mol Neurodegener ; 15(1): 49, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32900375

RESUMO

BACKGROUND: α-Synuclein (aSyn) aggregation is thought to play a central role in neurodegenerative disorders termed synucleinopathies, including Parkinson's disease (PD). Mouse aSyn contains a threonine residue at position 53 that mimics the human familial PD substitution A53T, yet in contrast to A53T patients, mice show no evidence of aSyn neuropathology even after aging. Here, we studied the neurotoxicity of human A53T, mouse aSyn, and various human-mouse chimeras in cellular and in vivo models, as well as their biochemical properties relevant to aSyn pathobiology. METHODS: Primary midbrain cultures transduced with aSyn-encoding adenoviruses were analyzed immunocytochemically to determine relative dopaminergic neuron viability. Brain sections prepared from rats injected intranigrally with aSyn-encoding adeno-associated viruses were analyzed immunohistochemically to determine nigral dopaminergic neuron viability and striatal dopaminergic terminal density. Recombinant aSyn variants were characterized in terms of fibrillization rates by measuring thioflavin T fluorescence, fibril morphologies via electron microscopy and atomic force microscopy, and protein-lipid interactions by monitoring membrane-induced aSyn aggregation and aSyn-mediated vesicle disruption. Statistical tests consisted of ANOVA followed by Tukey's multiple comparisons post hoc test and the Kruskal-Wallis test followed by a Dunn's multiple comparisons test or a two-tailed Mann-Whitney test. RESULTS: Mouse aSyn was less neurotoxic than human aSyn A53T in cell culture and in rat midbrain, and data obtained for the chimeric variants indicated that the human-to-mouse substitutions D121G and N122S were at least partially responsible for this decrease in neurotoxicity. Human aSyn A53T and a chimeric variant with the human residues D and N at positions 121 and 122 (respectively) showed a greater propensity to undergo membrane-induced aggregation and to elicit vesicle disruption. Differences in neurotoxicity among the human, mouse, and chimeric aSyn variants correlated weakly with differences in fibrillization rate or fibril morphology. CONCLUSIONS: Mouse aSyn is less neurotoxic than the human A53T variant as a result of inhibitory effects of two C-terminal amino acid substitutions on membrane-induced aSyn aggregation and aSyn-mediated vesicle permeabilization. Our findings highlight the importance of membrane-induced self-assembly in aSyn neurotoxicity and suggest that inhibiting this process by targeting the C-terminal domain could slow neurodegeneration in PD and other synucleinopathy disorders.

16.
Small ; : e2003508, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985135

RESUMO

Near-infrared (NIR) light-triggered hyperthermia has exhibited promising prospects in oncology therapy due to the unique merits including minimal invasiveness, monitorable, excellent therapeutic effect, and negligible side effects. Especially, the second NIR biowindow (NIR-II, 1000-1700 nm) with less absorbance and scattering by skin tissue, and deep tissue penetration, has received extensive attention for photonic hyperthermia. Unfortunately, the dissatisfactory photothermal conversion efficiency (PCE) and cumbersome preparation process of photo-driven heat conversion nanomaterials seriously hamper the future clinical application. To combat the aforementioned challenges, high imaging performance and desired therapeutic outcome 1D nanorods are constructed based on gadolinium-integrated tellurium nanorods (Te-Gd). In this system, magnetic resonance (MR) imaging and X-ray computed tomography (CT) imaging-guided photonic hyperthermia can be easily implemented in cooperation with Te-Gd. Importantly, Te-Gd possesses high PCE (41%) in the NIR-II biowindow because the transition of the excited electron can easily occur from the valence band (VB) to the conduction band (CB) on (1 0 1) and (1 0 2) crystal planes. Furthermore, the distinctive photostability, high tumor accumulation, as well as low systemic adverse effects of Te-Gd guarantee the potential in the clinic.

17.
Metabolism ; : 154349, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32888949

RESUMO

BACKGROUND: The functions of Acly in regulating nonalcoholic fatty liver disease (NAFLD) have been identified; however, the dynamic control of Acly expression under the pathological state of metabolic disorders has not been fully elucidated. Previous studies reported an ubiquitin-proteasome-mediated degradation of Acly, but the mechanism is still largely unknown. METHODS: Co-IP-based mass spectrum (MS/MS) assays were performed in HepG2 and Hepa1-6 hepatocytes and mouse liver tissue. The protein-protein interaction and ubiquitin modification of Hrd1 on Acly were confirmed by co-IP based immuno-blotting. Acetyl-CoA levels and lipogenesis rates were determined. The roles of Hrd1 on NAFLD and insulin resistance were tested by adenovirus-mediated overexpression in db/db mice or in separated primary hepatocytes. RESULTS: Hrd1, a subunit of the endoplasmic reticulum-associated degradation (ERAD) complex, interacted with and ubiquitinated Acly, thereby reducing its protein level. Hrd1 suppressed the acetyl-CoA level and inhibited lipogenesis through an Acly-dependent pathway. The expression of hepatic Hrd1 was negatively associated with NAFLD, whereas overexpression of Hrd1 ameliorated hepatic steatosis and enhanced insulin sensitivity, both in db/db mice and in separated mouse primary hepatocytes. CONCLUSIONS: Our results suggest that Acly, a master enzyme that regulates lipogenesis, is degraded by Hrd1 through ubiquitin modification. The activation of Hrd1 in hepatocytes might therefore represent a strategic approach for NAFLD therapy.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32881202

RESUMO

In the native wood cell wall, cellulose microfibrils are highly aligned and organized in the secondary cell wall. A new preparation strategy is developed to achieve individualization of cellulose microfibrils within the wood cell wall structure without introducing mechanical disintegration. The resulting mesoporous wood structure has a high specific surface area of 197 m2 g-1 when prepared by freeze-drying using liquid nitrogen, and 249 m2 g-1 by supercritical drying. These values are 5 to 7 times higher than conventional delignified wood (36 m2 g-1 ) dried by supercritical drying. Such highly mesoporous structure with individualized cellulose microfibrils maintaining their natural alignment and organization can be processed into aerogels with high porosity and high compressive strength. In addition, a strong film with a tensile strength of 449.1 ± 21.8 MPa and a Young's modulus of 51.1 ± 5.2 GPa along the fiber direction is obtained simply by air drying owing to the self-densification of cellulose microfibrils driven by the elastocapillary forces upon water evaporation. The self-densified film also shows high optical transmittance (80%) and high optical haze (70%) with interesting biaxial light scattering behavior owing to the natural alignment of cellulose microfibrils.

19.
J Virol ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878894

RESUMO

Subgroup J avian leukemia virus (ALV-J), belonging to the genus Alpharetrovirus, enters cells through its envelope surface unit (gp85) via specifically recognizing the cellular receptor chicken Na+/H+ exchanger type I (chNHE1), the 28-39 N-terminal residues of which were characterized as the minimal receptor functional domain in our previous studies. In this study, to further clarify the precise organization and properties of the interaction between ALV-J gp85 and chNHE1, we identified the chNHE1-binding domain of ALV-J gp85 using a series of gp85 mutants with segment substitutions and evaluating their effects on chNHE1-binding in protein-cell binding assays. Our results showed that HA substitutions of amino acids (aa) 38-131 (N-terminal of gp85) and aa 159-283 (C-terminal of gp85) significantly inhibited the interaction between gp85 and chNHE1/chNHE1 loop 1. In addition, these HA-substituted chimeric gp85 proteins could not effectively block the entry of ALV-J into chNHE1-expressing cells. Furthermore, analysis of various N-linked glycosylation site and cysteine mutants in gp85 revealed that glycosylation sites (N6 and N11) and cysteines (C3 and C9) were directly involved in receptor-gp85 binding and important for the entry of ALV-J into cells. Taken together, our findings indicated that the bipartite sequence motif, spanning aa 38-131 and aa 159-283, of ALV-J gp85 was essential for binding to chNHE1, with its two N-linked glycosylation sites and two cysteines being important for its receptor-binding function and subsequent viral infection steps.IMPORTANCE Infection of a cell by retroviruses requires the attachment and fusion of the host and viral membranes. The specific adsorption of env surface proteins to cell receptors is a key step in triggering infections and has been the target of antiviral drug screening. ALV-J is an economically important avian pathogen that belongs to the genus Alpharetrovirus and has a wider host range than other ALV subgroups. Our results showed that the amino acids 38-131 of the N-terminal and 159-283 of the C-terminal of ALV-J gp85 controlled the efficiency of gp85 binding to chNHE1 and were critical for viral infection. In addition, the glycosylation sites (N6 and N11) and cysteines (C9 and C9) of gp85 played a crucial role in the receptor binding and viral entry. These findings might help elucidate the mechanism of the entry of ALV-J into host cells and provide antiviral targets for the control of ALV-J.

20.
Infect Dis Poverty ; 9(1): 125, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867841

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) was one of the most important parasitic diseases in China, caused by Leishmania protozoans and transmitted by sand flies. Recently VL cases have reappeared in China, including the extension region of the Loess Plateau. The purpose of this study was to collect fundamental data on the host-vector VL system in the Loess Plateau to assist in the development of prevention and control measures. METHODS: Sand flies were collected by light traps from rural areas in Shanxian, Henan, China in 2015, as well as in Wuxiang and Yangquan, Shanxi, China in 2017. The blood sources of sand flies were analyzed by PCR detecting the host-specific mitochondrial cytochrome b (mtDNA cyt b) gene fragments. Leishmania infection in sand flies was detected by amplifying and sequencing ribosomal DNA internal transcribed spacer 1 (ITS1). The Leishmania specific antibodies in the sera of local dogs were detected by ELISA kit. RESULTS: Blood sources showed diversity in the extension region of the Loess Plateau, including human, chicken, dog, cattle, pig and goat. Multiple blood sources within a sand fly were observed in samples from Yangquan (17/118, 14.4%) and Wuxiang (12/108, 11.1%). Leishmania DNA was detected in sand flies collected from Yangquan with minimum infection rate of 1.00%. The ITS1 sequences were conserved with the Leishmania donovani complex. The positive rate of Leishmania specific antibodies in dogs was 5.97%. CONCLUSIONS: This study detected the blood sources and Leishmania parasites infection of sand flies by molecular methods in the extension region of Loess Plateau, China. A high epidemic risk of leishmaniasis is currently indicated by the results as the infection of Leishmania in sand flies, the extensive blood sources of sand flies including humans, and positive antibody of Leishmania in local dog sera. Given the recent increase of VL cases, asymptomatic patients, dogs and other potential infected animals should be screened and treated. Furthermore, the density of sand flies needs to be controlled and personal protection should be strengthened.

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