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1.
Cancer Lett ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33610731

RESUMO

Gene therapy promises to revolutionize biomedicine and personalized medicine by modulating or compensating the expression of abnormal genes. The biggest obstacle for clinical application is the lack of an effective, non-immunogenic delivery system. We show that bovine colostrum exosomes and polyethyleneimine matrix (EPM) delivers short interfering RNA (siRNA) or plasmid DNA (pDNA) for effective gene therapy. KRAS, a therapeutic focus for many cancers, was targeted by EPM-delivered KRAS siRNA (siKRAS) and inhibited lung tumor growth (>70%) and reduced KRAS expression (50%-80%). Aberrant p53 is another therapeutic focus for many cancers. EPM-mediated introduction of wild-type (WT) p53 pDNA (pcDNA-p53) resulted in p53 expression in p53-null H1299 cells in culture subcutaneous lung tumor, and tissues of p53-knockout mice. Additionally, chemo-sensitizing effects of paclitaxel were restored by exogenous WT p53 in lung cancer cells. Together, this novel EPM technology represents an effective 'platform' for delivery of therapeutic nucleic acids to treat human disease.

2.
Small ; : e2005752, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544971

RESUMO

Aromatic imides are a class of attractive organic materials with inherently electroactive groups and large π electron-deficient scaffolds, which hold potential as electrode materials for organic secondary batteries (OSBs). However, the undecorated aromatic imides are usually plagued by low capacity, high solubility in electrolyte, and poor electronic/ionic conductivity. Molecular engineering has been demonstrated to be an effective strategy to address unsatisfying characteristics of the aromatic imides, thereby expanding their scope for applications in OSBs. In this review, the recent research progress in modulation of the capacity, dissolution, and electronic/ionic conductivity of aromatic imides for organic lithium batteries, organic sodium batteries, and redox flow batteries are summarized. In addition, the challenge and prospective of aromatic imides in organic secondary battery applications are also discussed.

3.
PLoS Pathog ; 17(2): e1009291, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33529209

RESUMO

Acinetobacter baumannii is a highly antibiotic-resistant bacterial pathogen for which novel therapeutic approaches are needed. Unfortunately, the drivers of virulence in A. baumannii remain uncertain. By comparing genomes among a panel of A. baumannii strains we identified a specific gene variation in the capsule locus that correlated with altered virulence. While less virulent strains possessed the intact gene gtr6, a hypervirulent clinical isolate contained a spontaneous transposon insertion in the same gene, resulting in the loss of a branchpoint in capsular carbohydrate structure. By constructing isogenic gtr6 mutants, we confirmed that gtr6-disrupted strains were protected from phagocytosis in vitro and displayed higher bacterial burden and lethality in vivo. Gtr6+ strains were phagocytized more readily and caused lower bacterial burden and no clinical illness in vivo. We found that the CR3 receptor mediated phagocytosis of gtr6+, but not gtr6-, strains in a complement-dependent manner. Furthermore, hypovirulent gtr6+ strains demonstrated increased virulence in vivo when CR3 function was abrogated. In summary, loss-of-function in a single capsule assembly gene dramatically altered virulence by inhibiting complement deposition and recognition by phagocytes across multiple A. baumannii strains. Thus, capsular structure can determine virulence among A. baumannii strains by altering bacterial interactions with host complement-mediated opsonophagocytosis.

4.
J Sci Food Agric ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33570760

RESUMO

BACKGROUND: The conversion of arable land to grassland and/or forested land is a common strategy of restoration, because the development of plant communities can inhibit the erosion of soil, increase biodiversity and improve associated ecosystem services. The vertical profiles of microbial communities, however, have not been well characterized, and their variability after land conversion is not well understood. We assessed the effects of the conversion of arable land (AL) to grassland (GL) and forested land (FL) on bacterial communities as old as 29 years in 0-200 cm profiles of a Chinese Mollisol. RESULTS: The soil in AL has been a stable ecosystem, and changes in assembly of soil microbiomes tended to be larger in the topsoil. The soil properties and microbial biodiversity of arable land were larger following revegetation and reforestation. The conversion caused a more complex coupling among microbes, and negative interactions and average connectivity were stronger in the 0-20 cm layers in GL and in the 20-60 cm layers in FL. The land use dramatically influenced the assembly of the microbial communities more in GL than AL and FL. The bacterial diversity was an important component of soil multinutrient cycling in the profiles and that microbial functions were not as affected by changes in land use. CONCLUSION: The spatial variation of the microbiomes provided critical information on belowground soil ecology and the ability of the soil to provide crucial ecosystem services. This article is protected by copyright. All rights reserved.

5.
J Hematol Oncol ; 14(1): 30, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596982

RESUMO

Histone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.

6.
Biosci Rep ; 41(2)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33565572

RESUMO

Ferroptosis, a novel type of programmed cell death, is involved in inflammation and oxidation of various human diseases, including diabetic kidney disease. The present study explored the role of high-mobility group box-1 (HMGB1) on the regulation of ferroptosis in mesangial cells in response to high glucose. Compared with healthy control, levels of serum ferritin, lactate dehydrogenase (LDH), reactive oxygen species (ROS), malonaldehyde (MDA), and HMGB1 were significantly elevated in diabetic nephropathy (DN) patients, accompanied with deregulated ferroptosis-related molecules, including long-chain acyl-CoA synthetase 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (PTGS2), NADPH oxidase 1 (NOX1), and glutathione peroxidase 4 (GPX4). In vitro assay revealed that erastin and high glucose both induced ferroptosis in mesangial cells. Suppression of HMGB1 restored cellular proliferation, prevented ROS and LDH generation, decreased ACSL4, PTGS2, and NOX1, and increased GPX4 levels in mesangial cells. Furthermore, nuclear factor E2-related factor 2 (Nrf2) was decreased in DN patients and high glucose-mediated translocation of HMGB1 in mesangial cells. Knockdown of HMGB1 suppressed high glucose-induced activation of TLR4/NF-κB axis and promoted Nrf2 expression as well as its downstream targets including HO-1, NQO-1, GCLC, and GCLM. Collectively, these findings suggest that HMGB1 regulates glucose-induced ferroptosis via Nrf2 pathway in mesangial cells.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33565957

RESUMO

A Gram-stain-negative, aerobic, yellow, non-motile, rod-shaped and alginate-degrading bacterium, designated Dm15T, was isolated from marine alga collected in Weihai, PR China. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Dm15T represents a distinct line of the family Flavobacteriaceae. Strain Dm15T had the highest 16S rRNA gene sequence similarity to its closest phylogenetic neighbour Arcticiflavibacter luteus (96.7 %) and 93.7-96.4 % sequence similarity to other phylogenetic neighbours (Bizionia paragorgiae, Winogradskyella thalassocola, Ichthyenterobacterium magnum, Psychroserpens burtonensis and Arcticiflavibacter luteus) in the family Flavobacteriaceae. The novel isolate was able to grow at 10-40 °C (optimum, 30-33 °C), pH 7.0-9.0 (optimum, pH 7.0-7.5) and with 0.5-6.0 % NaCl (optimum 2.0-3.0 %, w/v). It could grow at 40 °C, and degrade alginate and cellulose, which were different from the neighbour genera. The draft genome consisted of 3395 genes with a total length of 3 798 431 bp and 34.1mol% G+C content. Especially, there were some specific genes coding for cellulase and alginate lyase, which provided a basis for the above phenotypic characteristics. The strain's genome sequence showed 71.1-80.2 % average amino acid identity values and 71.8-77.7 % average nucleotide identity values compared to the type strains of related genera within the family Flavobacteriaceae. It shared digital DNA-DNA hybridization identity of 19.8 and 20.9 % with I. magnum and A. luteus, respectively. The sole menaquinone was MK-6. The major fatty acids were iso-C15 : 0 and iso-C15 : 1 G. The polar lipids included six unidentified polar lipids, four unidentified aminolipids and phosphatidylethanolamine. Based on the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain Dm15T represents a novel species of a new genus in the family Flavobacteriaceae, phylum Bacteroidetes, for which the name Flavihalobacter algicola gen. nov., sp. nov. is proposed. The type strain is Dm15T (KCTC 42256T=CICC 23815T).

8.
Appl Spectrosc ; : 3702821999114, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599538

RESUMO

The chlorinity of deep-sea hydrothermal fluids, representing one of the crucial deep-sea hydrothermal indicators, indicates the degree of deep phase separation of hydrothermal fluids and water/rock reactions. However, accurately measuring the chlorinity of high-temperature hydrothermal fluids is still a significant challenge. In this paper, a piecewise chlorinity model to measure the chlorinity of high-temperature hydrothermal fluids was developed based on the OH stretching band of water, exhibiting an accuracy of 96.20%. The peak position, peak area ratio and F value were selected to establish the chlorinity piecewise calibration model within the temperature ranges of 0-50°C, 50-200°C and 200-300°C. Compared with that of the chlorinity calibration model built based on a single parameter, the accuracy of this piecewise model increased by approximately 4.83-12.33%. This chlorinity calibration model was applied to determine the concentrations of Cl for high-temperature hydrothermal fluids in the Okinawa Trough hydrothermal field.

9.
Chem Commun (Camb) ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599676

RESUMO

We report here the synthesis of a ferrocene-functionalized {Ti22Fc4} cluster with a 'dimer-of-clusters' topology, which represents the largest Ti-oxo cluster (TOC) modified with organometallic groups ever reported. The exact assembly path of {Ti22Fc4} can be inferred from its two substructures, {Ti11Fc2} and {Ti5Fc}, which can also be synthesized independently through subtle changes in reaction conditions. Furthermore, we used these clusters as photocatalysts, and have studied, for the first time, the photocatalytic activity of TOCs in the oxidative coupling of amines.

10.
Nat Commun ; 12(1): 1010, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579925

RESUMO

Electrochromic devices can modulate their light absorption under a small driving voltage, but the requirement for external electrical supplies causes response-lag. To address this problem, self-powered electrochromic devices have been studied recently. However, insensitivity to the surrounding light and unsatisfactory stability of electrochromic devices have hindered their critical applications. Herein, novel perovskite solar cell-powered all-in-one gel electrochromic devices have been assembled and studied in order to achieve automatic light adjustment. Two alkynyl-containing viologen derivatives are synthesized as electrochromic materials, the devices with very high stability (up to 70000 cycles) serves as the energy storage and smart window, while the perovskite solar cell with power-conversion-efficiency up to 18.3% serves as the light detector and power harvester. The combined devices can automatically switch between bleached and colored state to adjust light absorption with variable surrounding light intensity in real-time swiftly, which establish significant potentials for applications as modern all-day intelligent windows.

11.
Sci Adv ; 7(5)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33571109

RESUMO

The invasiveness and high immune suppression of glioblastoma multiforme (GBM) produce poor survival of afflicted patients. Unfortunately, in the past decades, no therapeutic approach has remarkably improved the survival time of patients with GBM. Our analysis of the TCGA database and brain tumor tissue arrays indicated that CXCL1 and CXCL2 overexpression is closely associated with GBM's aggressiveness. Our results showed that elevation of CXCL1 or CXCL2 facilitated myeloid cell migration and simultaneously disrupted CD8+ T cell accumulation at tumor sites, causing accelerated tumor progression. Yet, blockade of CXCL1/2 significantly prevented myeloid-derived suppressor cell migration and thereby increased CD8+ T cell accumulation in vitro and in vivo. CXCL1/2 also promoted the paracrine factor S100A9 and further activated Erk1/2 and p70S60k, whereas blocking CXCL1/2 down-regulated these prosurvival factors. The combination of targeting CXCL1/2 and standard temozolomide chemotherapy improved upon the antitumor efficacy of chemotherapy alone, extending the overall survival time in GBM.

12.
Nat Immunol ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574620
13.
J Comp Eff Res ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33576249

RESUMO

Aim: The study assesses the cost-effectiveness of empagliflozin versus glimepiride in patients with Type 2 diabetes and uncontrolled by metformin alone in China, based on the EMPA-REG H2H-SU trial. Materials & methods: A calibrated version of the IQVIA Core Diabetes Model was used. Cost of complications and utility were taken from literature. The Chinese healthcare system perspective and 5% discounting rates were applied. Results: Empagliflozin+metformin provides additional quality-adjusted life-years (0.317) driven by a reduction in the number of cardiovascular and renal events, for an additional cost of $1382 (CNY9703) compared with glimepiride+metformin. Conclusion: Empagliflozin is cost-effective treatment versus glimepiride applying a threshold of $30,290 (CNY212,676).

14.
Pediatr Cardiol ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591387

RESUMO

To review the early and intermediate outcomes of patients with transposition of the great arteries (TGA) and intramural coronary artery (IMCA) who underwent arterial switch operation (ASO) at our center. Among 450 patients with TGA who underwent an ASO between 2010 and 2018, 26 (5.8%) patients were identified with IMCA. The left coronary artery was intramural in 21 of 26 patients. We adopted coronary transfer using double coronary buttons with unroofed intramural course for all 26 patients. Early mortality for patients with IMCA was 3 of 26 (11.5%) compared with 10 of 424 (2.4%) for those without IMCA (p = 0.007). Six patients suffered major adverse events, including extracorporeal membrane oxygenation support in 3 patients, delayed sternal closure in 6 patients. The follow-up was available for all 23 survivors, with the mean follow-up period of 73.5 ± 28.7 months. There was no late death and reinterventions, and all patients were asymptomatic at last follow-up. One patient exhibited moderate neopulmonary regurgitation, and 1 patient presented with distal stenosis of the right pulmonary artery. Coronary transfer using double coronary buttons with unroofed intramural course was a good option for patients with TGA and IMCA. With this technique, ASO could be performed with optimal early and intermediate outcomes.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33591734

RESUMO

A binder is an important component in lithium-ion batteries and plays a significant role in maintaining the properties of active substances. Most studies in the field of binders have only focussed on physical properties such as bonding performance. Here, a polyacrylic acid-modified binder was designed and adapted to Li[Ni0.8Co0.1Mn0.1]O2, which enhanced the electrochemical stability of Li[Ni0.8Co0.1Mn0.1]O2 from 30.2 to 66.6% (300 cycles at 1 C). We for the first time discovered that this was caused by a chemical reaction between polyacrylic acid and the residual lithium on the surface during the cycling, which formed a lithium propionic acid coating layer and maintained the stability of the layered structure.

16.
Ann Thorac Surg ; 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33592183

RESUMO

BACKGROUND: The present study evaluated the surgical results of a diverse array of congenital heart defects through minimal right vertical infra-axillary incision (RVIAI). METHODS: A retrospective review of consecutive patients using minimal RVIAI for congenital heart defects between 2015 to 2019 was performed. The study included 1672 patients and the minimal RVIAI was utilized for 13 primary procedures. The length of incision ranged from 2.0 to 4.0 cm in all patients. RESULTS: Median age was 2.3 years (range, 0.2-6.0 years) and median weight was 12.5 kg (range, 5.0-34.0 kg). There was no in-hospital death or conversion to median sternotomy. Five patients (0.3%) underwent early reoperations (three had postoperative bleeding, one had coarctation of ascending aorta due to cannulation, and one had major residual shunt). Other postoperative complications included trivial residual shunt in 16 patients (1.0%), pleural effusion in 3 patients (0.2%), and wound infection in 4 patients (0.2%). Median follow-up was 3.2 years (range, 0.2-4.9 years). There were no late deaths or late reoperations. During the follow-up period, no surgery-related thoracic deformity or breast asymmetry were noted. One patient had mild scoliosis. We randomly chose 100 patients to complete questionnaire regarding patient satisfaction with minimal RVIAI. Results showed that all patients and their parents were satisfied with the cosmetic results. CONCLUSIONS: Minimal RVIAI can be safely performed for a wide range of congenital heart defects with excellent cosmetic results. It may serve as a good alternative to median sternotomy, especially for very young female patients.

17.
Dis Colon Rectum ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33538520

RESUMO

BACKGROUND: The current clinicopathological risk factors do not accurately predict disease recurrence in patients with T4N0M0 colon cancer. We hypothesized that the collagen signature combined with clinicopathological risk factors (new model) had a better prognostic value than clinicopathological risk factors alone (clinicopathological model). OBJECTIVE: This study aimed to establish a collagen signature in the tumor microenvironment and to validate its role in predicting the recurrence of T4N0M0 colon cancer. DESIGN: This was a retrospective study. SETTINGS: This study took place at a tertiary medical center. PATIENTS: Patients with T4N0M0 colon cancer who underwent surgery at our center between 2009 and 2015 (n=416) were included. INTERVENTION: A total of 142 collagen features were analyzed in the tumor microenvironment in specimens of colon cancer using second harmonic generation imaging. A collagen signature was constructed using a LASSO Cox regression model. MAIN OUTCOME MEASURES: Disease-free survival and overall survival. RESULTS: The training and testing cohorts consisted of 291 and 125 randomly assigned samples, with recurrence rates of 19.9% and 22.4%, respectively. A 3-feature-based collagen signature predicted the recurrence risk at 1, 3, and 5 years, with the area under the receiver-operating characteristic curves of 0.808, 0.832, and 0.791 in the training cohort and 0.836, 0.807, and 0.794 in the testing cohort, respectively. Multivariate analysis revealed that the collagen signature could independently predict the disease-free survival (HR=7.17, p<0.001) and overall survival rates (HR=5.03, p<0.001). The new model had a better prognostic value than the clinicopathological model, which included four clinicopathological risk factors: obstruction or perforation, lymphovascular invasion, tumor budding, and no chemotherapy. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: The collagen signature in the tumor microenvironment may be a new prognostic marker that can effectively predict the recurrence and survival of patients with T4N0M0 colon cancer. See Video Abstract at http://links.lww.com/DCR/B503 .

18.
IEEE Trans Cybern ; PP2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33507876

RESUMO

This article investigates an adaptive fuzzy tracking control approach via output feedback for a class of switched uncertain nonlinear systems with full-state constraints under arbitrary switchings. The adaptive observer and controller are designed based on fuzzy approximation. The main characteristic of discussed systems is that the state variables are not available for measurement and need to be kept within the constraint set. In order to estimate the unmeasured states, the adaptive fuzzy state observer is constructed. To guarantee that all the states do not violate the time-varying bounds, the tangent barrier Lyapunov functions (BLF-Tans) are selected in the design procedure. Based on the common Lyapunov function method, the stability of considered systems is analyzed. It is demonstrated that all the signals in the resulting system are bounded, and all the states are limited in their constrained sets. Furthermore, the simulation example is used to validate the effectiveness of the presented control strategy.

19.
Mol Plant Microbe Interact ; : MPMI03200071R, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33507814

RESUMO

Verticillium wilt is a vascular disease causing tremendous damage to cotton production worldwide. However, our knowledge of the mechanisms of cotton resistance or susceptibility to this disease is very limited. In this study, we compared the defense transcriptomes of cotton (Gossypium hirsutum) cultivars Shidalukang 1 (Verticillium dahliae resistant, HR) and Junmian 1 (V. dahliae susceptible, HS) before and after V. dahliae infection, identified hub genes of the network associated with responses to V. dahliae infection, and functionally characterized one of the hub genes involved in biosynthesis of lignin and phenolics. We identified 6,831 differentially expressed genes (DEGs) between the basal transcriptomes of HR and HS; 3,685 and 3,239 of these DEGs were induced in HR and HS, respectively, at different time points after V. dahliae infection. KEGG pathway analysis indicated that DEGs were enriched for genes involved in lignin biosynthesis. In all, 23 hub genes were identified based on a weighted gene coexpression network analysis of the 6,831 DEGs and their expression profiles at different time points after V. dahliae infection. Knockdown of Gh4CL30, one of the hub genes related to the lignin biosynthesis pathway, by virus-induced gene silencing, led to a decreased content of flavonoids, lignin, and S monomer but an increased content of G monomer, G/S lignin monomer, caffeic acid, and ferulic acid, and enhanced cotton resistance to V. dahliae. These results suggest that Gh4CL30 is a key gene modulating the outputs of different branches of the lignin biosynthesis pathway, and provide new insights into cotton resistance to V. dahliae.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

20.
Int J Cancer ; 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33497467

RESUMO

The biological activities of chemokine (C-C motif) ligand 2 (CCL2) are mediated via C-C chemokine receptor-2 (CCR2). Increased CCL2 level is associated with metastasis of many cancers. In our study, we investigated the role of the CCL2/CCR2 axis in the development of spontaneous intestinal tumorigenesis using the ApcMin/+ mouse model. Ablation of CCR2 in ApcMin/+ mice significantly increased the overall survival and reduced intestinal tumor burden. Immune cell analysis showed that CCR2-/- ApcMin/+ mice exhibited significant reduction in the myeloid cell population and increased interferon γ (IFN-γ) producing T cells both in spleen and mesenteric lymph nodes compared to ApcMin/+ mice. The CCR2-/- ApcMin/+ tumors showed significantly reduced levels of interleukin (IL)-17 and IL-23 and increased IFN-γ and Granzyme B compared to ApcMin/+ tumors. Transfer of CCR2+/+ ApcMin/+ CD4+ T cells into Rag2-/- mice led to development of colitis phenotype with increased CD4+ T cells hyper proliferation and IL-17 production. In contrast, adoptive transfer of CCR2-/- ApcMin/+ CD4+ T cells into Rag2-/- mice failed to enhance colonic inflammation or IL-17 production. These results a suggest novel additional role for CCR2, where it regulates migration of IL-17 producing cells mediating tumor-promoting inflammation in addition to its role in migration of tumor associated macrophages.

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