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1.
Artigo em Inglês | MEDLINE | ID: mdl-33006880

RESUMO

Blood vessel damage resulting from trauma or diseases presents a serious risk of morbidity and mortality. Although synthetic vascular grafts have been successfully commercialized for clinical use, they are currently only readily available for large-diameter vessels (>6 mm). Small-diameter vessel (<6 mm) replacements, however, still present significant clinical challenges worldwide. The primary objective of this study is to create novel, tunable, small-diameter blood vessels with biomimetic two distinct cell layers [vascular endothelial cell (VEC) and vascular smooth muscle cell (VSMC)] using an advanced coaxial 3D-bioplotter platform. Specifically, the VSMCs were laden in the vessel wall and VECs grew in the lumen to mimic the natural composition of the blood vessel. First, a novel bioink consisting of VSMCs laden in gelatin methacryloyl (GelMA)/polyethylene(glycol)diacrylate/alginate and lyase was designed. This specific design is favorable for nutrient exchange in an ambient environment and simultaneously improves laden cell proliferation in the matrix pore without the space restriction inherent with substance encapsulation. In the vessel wall, the laden VSMCs steadily grew as the alginate was gradually degraded by lyase leaving more space for cell proliferation in matrices. Through computational fluid dynamics simulation, the vessel demonstrated significantly perfusable and mechanical properties under various flow velocities, flow viscosities, and temperature conditions. Moreover, both VSMCs in the scaffold matrix and VECs in the lumen steadily proliferated over time creating a significant two-cell-layered structure. Cell proliferation was confirmed visually through staining the markers of alpha-smooth muscle actin and cluster of differentiation 31, commonly tied to angiogenesis phenomena, in the vessel matrices and lumen, respectively. Furthermore, the results were confirmed quantitatively through gene analysis which suggested good angiogenesis expression in the blood vessels. This study demonstrated that the printed blood vessels with two distinct cell layers of VECs and VSMCs could be potential candidates for clinical small-diameter blood vessel replacement applications.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33009695

RESUMO

Electrocatalytic conversion of carbon dioxide into high-value multi-carbon (C2+) chemical feedstocks offers a promising avenue to liberate the chemical industry from fossil-resource dependence and eventually close the anthropogenic carbon cycle, but is severely impeded by the lack of high-performance catalysts. Herein, aiming to break the linear scaling relationship of intermediates binding and minimize the kinetic barrier of CO2 reduction reactions (CO2 RR), ternary Cu-Au/Ag nanoframes are fabricated to decouple the two pivotal functions of CO generation and C-C coupling, where the former is greatly promoted by the alloyed Ag/Au substrate and the latter is elegantly facilitated by the highly strained and positively charged Cu domains. Thereby, extraordinary Faradic efficiencies of 69 ± 5% and 77 ± 2% on C2H4 production in H-cell and flow cell, respectively, are achieved with great electrocatalytic stability and material durability. In-situ IR and DFT calculations unveil two competing pathways for C2H4 generation, of which the direct CO dimerization is energetically favored. By integrating the tandem effect, electronic modulation, and defect engineering, the current study offers a paradigm in catalyst design to break the linear scaling relationship towards improved C2H4 production.

3.
ChemMedChem ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32964625

RESUMO

Since the initial discovery as nicotinic acetylcholine receptor ligands, the 3-alkoxyisoxazole scaffold has now been shown as a versatile platform for the development of potent σ1 and σ2 receptor ligands. Herein we report a further SAR exploration on the 3-alkoxyisoxazole scaffold with the aim of obtaining potent σ2 receptor ligands. Various substitutions on the benzene ring and the basic amino regions resulted in a total of 21 compounds that were tested for their binding affinities to σ2 receptor. In particular, compound 51 was identified as one of the most potent σ2 ligands within the series with a K i value of 7.9 nM, and demonstrated potent anti-proliferative effects on the both osteosarcoma cell lines 143B and MOS-J (IC 50 values of 0.89 and 0.71 µM, respectively), compared to siramesine (IC 50 values of 1.81 and 2.01 µM). Moreover, compound 51 inhibited the clonal formation of the osteosarcoma 143B cells at 1 µM concentration, corresponding to half the dose required of siramesine for similar effects. The general cytotoxicity profile of compound 51 was assessed in a number of normal cell lines, including HaCaT, HAF, and LO2 cells. Furthermore, FACS analysis showed that compound 51 likely inhibits the osteosarcoma cell growth by disruption of the cell cycle and promotion of cell apoptosis.

4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(4): 491-496, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895101

RESUMO

Objective To investigate the value of head and neck CT angiography(CTA)in the evaluation of intraoperative hemorrhage of carotid body tumours. Methods Head and neck CTA images of 36 patients with carotid body tumours confirmed by pathology were retrospectively analyzed.Patients were divided into two groups based on the intraoperative bleeding volume:<500 ml and≥500 ml groups.The patient's age,sex,Shamblin classification,size of the lesion,number of blood supply arteries,course of the disease,plain scan,and enhanced CT value between two groups were compared and analyzed.Logistics regression equation was established based on the CTA parameters with significant differences between the two intraoperative bleeding volume groups,and combined parameter was acquired.The receiver operating characteristic curve was established based on CTA single and combined parameters. Results The bleeding volume during the operation of carotid body tumors was significantly correlated with the age of patients(P=0.019),the maximum diameter of tumours on axial images(P=0.003),the maximum upper and lower diameters(P=0.004),Shamblin classification(P=0.012),and number of blood supply arteries(P<0.001).The area under the receiver operating characteristic curve of the number of feeding arteries,the maximum diameter of axial images,maximum upper and lower diameters,Shamblin classification,and combined parameters were 0.865,0.781,0.806,0.766,and 0.927,respectively.When the optimal critical value was 0.408,the Youden index was 0.794,and the corresponding accuracy,sensitivity,and specificity were 0.919,0.909,and 0.923,respectively. Conclusions Preoperative head and neck CTA can be used to evaluate the intraoperative blood loss.Combined parameters has the best diagnostic performance compared with single parameters.


Assuntos
Tumor do Corpo Carotídeo , Angiografia por Tomografia Computadorizada , Tumor do Corpo Carotídeo/diagnóstico por imagem , Cabeça , Humanos , Pescoço , Estudos Retrospectivos
5.
Abdom Radiol (NY) ; 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32918577

RESUMO

PURPOSE: To compare the diagnostic performance of PI-RADS version 2.1 (PI-RADS v2.1) and PI-RADS v2 for transition zone prostate cancer (TZPC), and analyse its performance for readers with different experience levels. METHODS: Eighty-five patients with suspected prostate cancer who underwent biopsy after MRI scan between January and December 2017 were retrospectively enrolled. One junior radiologist (reader 1, 1 year of experience in using PI-RADS v2) and one senior radiologist (reader 2, 6 years of experience) independently reviewed and assigned a score for each lesion according to PI-RADS v2.1 and v2. The template-guided transperineal prostate biopsy was used for standard of reference. To compare the diagnostic performance of the two methods, the AUC was calculated. The sensitivity, specificity, and accuracy were calculated at predefined positive values (PI-RADS ≥ 3). The interreader agreement and frequency of prostate cancer for each PI-RADS category were also calculated. RESULTS: Among the 85 patients, 27 had prostate cancers, and 25 were clinically significant prostate cancer (csPCa). The AUC values for diagnosing clinically significant prostate cancer significantly increased with PI-RADS v2.1 for reader 2 (0.766 vs. 0.902, P = 0.009). The specificity and accuracy for both readers also increased with PI-RADS v2.1 (specificity: reader 1, 41.7% vs. 78.3% and reader 2, 33.3% vs. 81.7%; accuracy: reader 1, 52.9% vs. 76.5% and reader 2, 48.2% vs. 83.5%, all P < 0.05). The interreader agreement was good for both versions. The percentage of prostate cancer decreased in lower PI-RADS categories (PI-RADS 2) and increased in higher PI-RADS categories (PI-RADS 3 ~ 4). CONCLUSION: Compared with PI-RADS v2, PI-RADS v2.1 may improve radiologists' diagnostic performance for TZPC.

6.
Cell Death Differ ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908202

RESUMO

Tauopathies are a group of neurodegenerative diseases characterized by hyperphosphorylation of the microtubule-binding protein, tau, and typically feature axon impairment and synaptic dysfunction. Cyclin-dependent kinase5 (Cdk5) is a major tau kinase and its activity requires p35 or p25 regulatory subunits. P35 is subjected to rapid proteasomal degradation in its membrane-bound form and is cleaved by calpain under stress to a stable p25 form, leading to aberrant Cdk5 activation and tau hyperphosphorylation. The type Ib transmembrane protein RPS23RG1 has been implicated in Alzheimer's disease (AD). However, physiological and pathological roles for RPS23RG1 in AD and other tauopathies are largely unclear. Herein, we observed retarded axon outgrowth, elevated p35 and p25 protein levels, and increased tau phosphorylation at major Cdk5 phosphorylation sites in Rps23rg1 knockout (KO) mice. Both downregulation of p35 and the Cdk5 inhibitor roscovitine attenuated tau hyperphosphorylation and axon outgrowth impairment in Rps23rg1 KO neurons. Interestingly, interactions between the RPS23RG1 carboxyl-terminus and p35 amino-terminus promoted p35 membrane distribution and proteasomal degradation. Moreover, P301L tau transgenic (Tg) mice showed increased tau hyperphosphorylation with reduced RPS23RG1 levels and impaired axon outgrowth. Overexpression of RPS23RG1 markedly attenuated tau hyperphosphorylation and axon outgrowth defects in P301L tau Tg neurons. Our results demonstrate the involvement of RPS23RG1 in tauopathy disorders, and implicate a role for RPS23RG1 in inhibiting tau hyperphosphorylation through homeostatic p35 degradation and suppression of Cdk5 activation. Reduced RPS23RG1 levels in tauopathy trigger aberrant Cdk5-p35 activation, consequent tau hyperphosphorylation, and axon outgrowth impairment, suggesting that RPS23RG1 may be a potential therapeutic target in tauopathy disorders.

7.
Int J Med Robot ; : e2162, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32881221

RESUMO

BACKGROUND: Traditional fracture reduction surgery cannot ensure the accuracy of the reduction while consuming the physical strength of the surgeon. Although monitoring the fracture reduction process through radiography can improve the accuracy of the reduction, it will bring radiation harm to both patients and surgeons. METHODS: We proposed a novel fracture reduction solution that parallel robot is used for fracture reduction surgery. The binocular camera indirectly obtains the position and posture of the fragment wrapped by the tissue by measuring the posture of the external markers. According to the clinical experience of fracture reduction, a path is designed for fracture reduction. Then using position-based visual serving control the robot to fracture reduction surgery. The study is approved by the ethics committee of the Rehabilitation Hospital, National Research Center for Rehabilitation Technical Aids, Beijing, China. RESULTS: Ten virtual cases of fracture were used for fracture reduction experiments. The simulation and model bone experiments are designed respectively. In model bone experiments, the fragments are reduced without collision. The angulation error after the reduction of this method is 3.3° ± 1.8°, and the axial rotation error is 0.8° ± 0.3°, the transverse stagger error and the axial direction error after reduction is 2 ± 0.5 mm and 2.5 ± 1 mm. After the reduction surgery, the external fixator is used to assist the fixing, and the deformity will be completely corrected. CONCLUSIONS: The solution can perform fracture reduction surgery with certain accuracy and effectively reduce the number of radiographic uses during surgery, and the collision between fragments is avoided during surgery.

8.
IEEE Trans Cybern ; PP2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32915761

RESUMO

While designing control for a class of underactuated mechanical systems (UMSs), the uncertainty and the prescribed nonholonomic tracking trajectories should be taken into consideration. Uncertainty considered in this article is time varying and bounded, and the bound of uncertainty is described using the fuzzy set theory, namely, fuzzy UMSs. An analytical dynamics-based view is taken in which the prescribed tracking trajectories are viewed as servo constraints which can be linear, nonlinear, holonomic, and nonholonomic. Using this view, a novel closed form solution of adaptive robust control is found with leakage type adaptive law to guarantee deterministic system performance, including uniform boundedness and uniform ultimate boundedness. In order to find the optimal dual gain parameters of the designed control, a two-player cooperative game is proposed for which the Pareto optimality can always be guaranteed. The effectiveness of the proposed control is shown through numerical simulation of a two-wheeled inverted pendulum vehicle.

9.
Cell Mol Neurobiol ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32989585

RESUMO

Opioids, like morphine and naloxone, regulate the proliferation and neuronal differentiation of neural stem cells (NSCs) in a receptor-independent and ten-eleven translocation methylcytosine dioxygenase (TET1)-dependent manner in vitro. Whether naloxone regulates hippocampal NSCs and contextual learning in vivo in a similar manner was determined. Naloxone infusion increased the Ki67 and Doublecortin positive cells in subgranular zone of wild type mice, which suggested the increased proliferation and differentiation of hippocampal NSCs in vivo and was consistent with the in vitro functions of naloxone. In addition, naloxone infusion also facilitated the contextual learning and memory of wild type mice. To determine the contribution of µ-opioid receptor (OPRM1) and TET1 to these functions of naloxone, several types of knockout mice were used. Since Tet1-/- mice have high deficiency in contextual learning and memory, Tet1+/- mice were used instead. The abilities of naloxone to regulate NSCs and to facilitate contextual learning were significantly impaired in Tet1+/- mice. In addition, these abilities of naloxone were not affected in Oprm1-/- mice. Therefore, naloxone facilitates contextual learning and memory in a receptor-independent and Tet1-dependent manner, which provides new understanding on the receptor-independent functions of opioids.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32998166

RESUMO

BACKGROUND: The present study aimed to compare the effectiveness and safety of low molecular-weight-heparin (LMWH) and unfractionated heparin (UFH) in acute myocardial infarction (AMI) patients receiving intra-aortic balloon counterpulsation (IABP). MATERIALS AND METHODS: We retrospectively analyzed a total of 344 patients receiving IABP for cardiogenic shock, severe heart failure, ventricular septal rupture, or mitral valve prolapse due to AMI. A total of 161 patients received UFH (a bolus injection 70 U/kg immediately after IABP, followed by infusion at a rate of 15 U/kg/hour and titration to for 50 to 70 seconds of activated partial thromboplastin time. A total of 183 patients received LMWH (subcutaneous injection of 1.0 mg/kg every 12 hours for 5 to 7 days and 1.0 mg/kg every 24 hours thereafter). Events of ischemia, arterial thrombosis or embolism, and bleeding during IABP were evaluated. Major bleeding was defined as a hemoglobin decrease by >50 g/L (vs. prior to IABP) or bleeding that caused hemodynamic shock or life-threatening or requiring blood transfusion. RESULTS: Subjects receiving UFH and LMWH did not differ in baseline characteristics. Ischemia was noted in five (3.1%) and two (1.1%) subjects in UFH and LMWH groups, respectively. Arterial thromboembolism occurred in three (1.9%) subjects in the UFH group, but not in the LMWH group. Logistic regression analysis failed to reveal an association between ischemia or bleeding with heparin type. Major bleeding occurred in 16 (9.9%) and six (3.3%) patients in the UFH and LWMH groups, respectively (p = 0.014). Regression analysis indicated that LMWH is associated with less major bleeding. CONCLUSION: LMWH could reduce the risk of major bleeding in patients receiving IABP. Whether LMWH could reduce arterial thromboembolism needs further investigation.

11.
BMC Plant Biol ; 20(1): 447, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993512

RESUMO

BACKGROUND: To explore the molecular regulatory mechanisms of early stem and leaf development, proteomic analysis was performed on leaves and stems of F genotype alfalfa, with thin stems and small leaves, and M genotype alfalfa, with thick stems and large leaves. RESULTS: Based on fold-change thresholds of > 1.20 or < 0.83 (p < 0.05), a large number of proteins were identified as being differentially enriched between the M and F genotypes: 249 downregulated and 139 upregulated in stems and 164 downregulated and 134 upregulated in leaves. The differentially enriched proteins in stems were mainly involved in amino acid biosynthesis, phenylpropanoid biosynthesis, carbon fixation, and phenylalanine metabolism. The differentially enriched proteins in leaves were mainly involved in porphyrin and chlorophyll metabolism, phenylpropanoid biosynthesis, starch and sucrose metabolism, and carbon fixation in photosynthetic organisms. Six differentially enriched proteins were mapped onto the porphyrin and chlorophyll metabolism pathway in leaves of the M genotype, including five upregulated proteins involved in chlorophyll biosynthesis and one downregulated protein involved in chlorophyll degradation. Eleven differentially enriched proteins were mapped onto the phenylpropanoid pathway in stems of the M genotype, including two upregulated proteins and nine downregulated proteins. CONCLUSION: Enhanced chlorophyll synthesis and decreased lignin synthesis provided a reasonable explanation for the larger leaves and lower levels of stem lignification in M genotype alfalfa. This proteomic study aimed to classify the functions of differentially enriched proteins and to provide information on the molecular regulatory networks involved in stem and leaf development.

12.
EBioMedicine ; 60: 102990, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32927274

RESUMO

BACKGROUND: Although TP53 co-mutation with KRAS/ATM/EGFR/STK11 have been proved to have predictive value for response to immune checkpoint inhibitors (ICIs), not all TP53 mutations are equal in this context. As the main part of TP53 mutant types, Missense and Nonsense alternations in TP53 as independent factors to predict the response to ICIs within Lung Adenocarcinoma (LUAD) patients have not yet been reported. METHODS: An integrated analysis based on multiple-dimensional data types including genomic, transcriptomic, proteomic and clinical data from published lung adenocarcinoma data and local database of LUAD taking immune checkpoint inhibitors. Gene set enrichment analysis (GSEA) was used to determine potentially relevant gene expression signatures between specific subgroups. Single-sample GSEA (GSVA) is conducted to calculate the score for enrichment of a set of genes regulating DNA damage repair (DDR) pathway. FINDINGS: The TP53-missense-mutation group showed increased PD-L1 (CD274) level and enriched IFN-γ signatures compared with the TP53-wild-type subgroup, but no differences were noted in patients with nonsense-mutant vs wild-type p53. Furthermore, a group of suppressor Immune cells like M2 Macrophage and Neutrophils are found enriched in nonsense group. On the other-side, both TP53 missense and nonsense mutations are associated with elevated TMB and neoantigen levels and contribute equally to DNA damage repair deficiency. The distribution regarding to multi-dimensional factors determining the efficacy of ICIs finally transformed into diverse clinical benefits for LUAD. TP53 missense but not -nonsense Mutants are associated with better clinical benefits taking antiPD-1/1L. However, all such TP53 subgroups responds well to nivolumab (antiPD-L1) plus ipilimumab (antiCTLA-4) therapy. INTERPRETATION: Our study demonstrated that not all TP53 mutations are equal in predicting efficacy in patients with LUAD treated with ICIs. Multi-center data showed that TP53 missense and nonsense mutations were significantly different in terms of associations with PD-L1 expression, IFN-γ signatures and TME composition. Special attention should be paid to potential TP53 mutation heterogeneity when evaluating TP53 status as biomarker for ICIs. FUNDING: The study was supported by Key Lab System Project of Guangdong Science and Technology Department - Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120, to Yi-Long WU).

14.
Clin Neurol Neurosurg ; 198: 106233, 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32977247

RESUMO

BACKGROUND: Argatroban in acute noncardioembolic stroke ineligible for intravenous thrombolysis (IVT) or endovascular treatment (EVT) remains unclear. This study aimed to evaluate whether argatroban improved early and long-term outcomes compared with antiplatelet treatment. METHODS: This retrospective observational study, using the prospective stroke database from our hospital, included all consecutive patients who hospitalized from January 1, 2017 to December 31, 2019, with a diagnosis of acute non-cardioembolic stroke within 48 hours of stroke onset but not receiving IVT and EVT. Patients were divided into 2 groups: the argatroban group and the control group without argatroban. Outcome assessment with early neurological deterioration (END), National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), bleeding complications, and mortality were compared between the 2 groups in all cases and different stroke subtypes. An ordinal logistic regression analysis evaluated the association between argatroban use and mRS score at 90 days. RESULTS: Of 1325 patients were enrolled, 519 patients in the argatroban group and 806 in the control. Baseline characteristics, hospital bleeding complications, and 90-day mortality were similar for the 2 groups. The argatroban group showed lower END, larger improvement of 7-day NIHSS score and higher percentage of a 90-day mRS score of 02. Similar results were found in subgroup analysis with large-artery atherosclerosis, anterior circulation infarction, and moderate stroke. Also, argatroban use was significantly associated with an excellent long-term stroke outcome (mRS ≤ 2). CONCLUSION: The current study suggested that argatroban was safe and effective for improving short and long-term outcomes in noncardioembolic stroke patients.

15.
Invest Ophthalmol Vis Sci ; 61(10): 38, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32821914

RESUMO

Purpose: Elevation of IOP in POAG is thought to involve excessive accumulation of extracellular matrix in the trabecular meshwork (TM), leading to an increase in outflow resistance of the aqueous humor. Osthole, a coumarin derivative extracted from the fruit of a variety of plants, such as Cnidium monnieri, is reported to prevent profibrotic responses by inhibiting Smad signaling pathway activated by TGF-ß in liver, kidney, and cardiac tissues. We tested if osthole can (1) inhibit TGF-ß2-induced extracellular matrix expression in cultured human TM (HTM) cells, and (2) lower TGF-ß2-induced ocular hypertension in the mouse. Methods: Cultured HTM cells were treated with 5 ng/mL TGF-ß2 for 48 hours, then with osthole for 24 hours. The expressions of fibronectin, collagen type IV, and laminin were assessed by quantitative PCR, Western blot, and immunocytochemistry. BALB/cJ mice were injected intravitreally with an adenoviral vector encoding a bioactive mutant of TGF-ß2 (Ad.hTGF-ß2226/228) in one eye to induce ocular hypertension, with the uninjected contralateral or Ad.Empty-injected eye serving as controls. Mice were then treated with a daily intraperitoneal injection of 30 mg/kg osthole. Conscious mouse IOP values were measured using a TonoLab rebound tonometer. Results: In cultured HTM cells, stimulation with TGF-ß2 increased expressions of fibronectin, collagen IV, and laminin. These in vitro changes were significantly and completely mitigated by osthole (10 µM). Daily intraperitoneal injections of 30 mg/kg osthole, starting either at day 0 (same day as Ad.hTGF-ß2226/228 injection) or at day 14, significantly decreased TGF-ß2-induced ocular hypertension in the mouse. In contrast, osthole did not affect IOP of control eyes. Conclusions: These results demonstrated that osthole is capable of reducing TGF-ß2-induced extracellular matrix expression in cultured HTM cells. It also reduced TGF-ß2-induced ocular hypertension in the mouse. These findings indicate that this natural product may be useful as a novel treatment for POAG.

16.
Cell Death Dis ; 11(8): 683, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32826860

RESUMO

Treating corneal endothelial diseases tends to be challenging as human corneal endothelial cells (CECs) do not proliferate in vivo. The pathogenesis or mechanisms underlying injured CECs need further studies. The abnormal expression of PAX6, which is an essential transcription factor for corneal homeostasis, exhibits corneal endothelial defects. However, the effects of PAX6 protein involved in corneal endothelial wound process are still unknown. Here, we found the upregulated protein levels of PAX6 in human corneal endothelial monolayer after injury; the expression of PAX6 also increased in murine and rat corneal endothelium injury models. Enforced PAX6 expression could alleviate the damages to CECs via regulating permeability by prompting cellular tight junction. In addition, SUMOylation mainly happened on both K53 and K89 residues of 48-kD PAX6 (the longest and main isoform expressed in cornea), and de-SUMOylation promoted the stability of PAX6 protein in vitro. In CECs of SENP1+/- mice, increased SUMOylation levels leading to instability and low expression of PAX6, delayed the repair of CECs after injury. Furthermore, overexpression of PAX6 accelerated the rate of corneal endothelial repair of SENP1+/- mice. Our findings indicate that SENP1-mediated de-SUMOylation improving the stability of PAX6, amplifies the protective effects of PAX6 on corneal endothelial injuries, highlighting potentials of PAX6 and/or SUMOylation to be used as a treatment target for corneal endothelial disorders.

17.
Chem Asian J ; 15(19): 2984-2991, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32789973

RESUMO

Electrolysis of water is a promising way to produce hydrogen fuel in large scale. The commercialization of this technology requires highly efficient non-noble metal electrocatalysts to decease the energy input for the hydrogen evolution reaction (HER). In this work, a novel nanowire structured molybdenum-tungsten bimetallic oxide (CTAB-D-W4 MoO3 ) is synthesized by a simple hydrothermal method followed with post annealing treatment. The obtained metal oxides feature with enhanced conductivity, rich oxygen vacancies and customized electronic structure. As such, the composite electrocatalyst exhibits excellent electrocatalytic performance for HER in an acidic environment, achieving a large current density of 100 mA cm-2 at overpotential of only 286 mV and a small Tafel slope of 71.2 mV dec-1 . The excellent electrocatalytic HER performance of CTAB-D-W4 MoO3 is attributed to the unique nanowire structure, rich catalytic active sites and promoted electron transfer rate.

19.
Bull Environ Contam Toxicol ; 105(3): 387-392, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32757041

RESUMO

Systematic studies on the impact of environmental pollution on the survival adaptability of amphibians are relatively few. In this study, Bufo raddei tadpoles from two places with totally different backgrounds of heavy metal pollution were chosen to explore the effects of heavy metal pollution on fitness and swimming performance of tadpoles, the physiological effects were investigated as well. The tadpoles at GS 25, GS 30 and GS 35 were collected randomly from the two study sites and were exposed to different environmental temperatures. The results showed that heavy metal enrichment and antioxidant levels were significantly higher in the tadpoles under long-term heavy metal stress. Meanwhile, heavy metal pollution affected the adaptability of tadpoles to environmental change and decreased the swimming performance of the tadpoles. Unexpected, the tadpoles from heavy metal-polluted area also showed some adaptive changes, mainly reflected in the increase in swimming endurance.


Assuntos
Larva/fisiologia , Metais Pesados/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Bufonidae , Poluentes Ambientais , Poluição Ambiental , Larva/efeitos dos fármacos , Metais Pesados/análise , Natação
20.
Nat Protoc ; 15(9): 3009-3029, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32796939

RESUMO

Genome editing holds great potential for correcting pathogenic mutations. We developed a method called GOTI (genome-wide off-target analysis by two-cell embryo injection) to detect off-target mutations by editing one blastomere of two-cell mouse embryos using either CRISPR-Cas9 or base editors. GOTI directly compares edited and non-edited cells without the interference of genetic background and thus could detect potential off-target variants with high sensitivity. Notably, the GOTI method was designed to detect potential off-target variants of any genome editing tools by the combination of experimental and computational approaches, which is critical for accurate evaluation of the safety of genome editing tools. Here we provide a detailed protocol for GOTI, including mice mating, two-cell embryo injection, embryonic day 14.5 embryo digestion, fluorescence-activated cell sorting, whole-genome sequencing and data analysis. To enhance the utility of GOTI, we also include a computational workflow called GOTI-seq (https://github.com/sydaileen/GOTI-seq) for the sequencing data analysis, which can generate the final genome-wide off-target variants from raw sequencing data directly. The protocol typically takes 20 d from the mice mating to sequencing and 7 d for sequencing data analysis.


Assuntos
Embrião de Mamíferos/metabolismo , Edição de Genes/métodos , Animais , Feminino , Injeções , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação
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