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1.
J Nanosci Nanotechnol ; 20(2): 900-908, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383085

RESUMO

A series of polyurethane hydrogel and polyurethane thermoplastic elastomer composite based separation membranes were successfully prepared via wet phase inversion method. The morphology, chemical structure, phase transition temperature and crystallinity of the polyurethane (PU) membranes were characterized by SEM, FTIR, DSC, and XRD, respectively. The SEM observation showed that the PU membranes exhibited irregular porous structure on the surface and path of the hole was flexural and asymmetrical in cross-section. The FTIR analysis demonstrated that thermalsensitive groups and pH-sensitive components (-N(CH3)-) were incorporated into the PU network. The DSC experiment and XRD experiment showed that the regular arrangement of PU network was destroyed partly due to the introduction of polyurethane thermoplastic elastomer. The equilibrium swelling ratio (ESR) and water flux (J) for PU membranes clearly decreased and increased with functional groups and sophisticated structure of PU membranes, respectively. In addition, the permeation experiments indicated that the permeation percentage (P) of the glycine was strongly affected by the external temperature and pH value.

2.
Cell ; 179(2): 561-577.e22, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31585088

RESUMO

We performed the first proteogenomic characterization of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using paired tumor and adjacent liver tissues from 159 patients. Integrated proteogenomic analyses revealed consistency and discordance among multi-omics, activation status of key signaling pathways, and liver-specific metabolic reprogramming in HBV-related HCC. Proteomic profiling identified three subgroups associated with clinical and molecular attributes including patient survival, tumor thrombus, genetic profile, and the liver-specific proteome. These proteomic subgroups have distinct features in metabolic reprogramming, microenvironment dysregulation, cell proliferation, and potential therapeutics. Two prognostic biomarkers, PYCR2 and ADH1A, related to proteomic subgrouping and involved in HCC metabolic reprogramming, were identified. CTNNB1 and TP53 mutation-associated signaling and metabolic profiles were revealed, among which mutated CTNNB1-associated ALDOA phosphorylation was validated to promote glycolysis and cell proliferation. Our study provides a valuable resource that significantly expands the knowledge of HBV-related HCC and may eventually benefit clinical practice.

3.
Mol Psychiatry ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31576007

RESUMO

Compelling evidence suggests that synaptic structural plasticity, driven by remodeling of the actin cytoskeleton, underlies addictive drugs-induced long-lasting behavioral plasticity. However, the signaling mechanisms leading to actin cytoskeleton remodeling remain poorly defined. DNA methylation is a critical mechanism used to control activity-dependent gene expression essential for long-lasting synaptic plasticity. Here, we provide evidence that DNA methyltransferase DNMT3a is degraded by the E2 ubiquitin-conjugating enzyme Ube2b-mediated ubiquitination in dorsal hippocampus (DH) of rats that repeatedly self-administrated heroin. DNMT3a degradation leads to demethylation in CaMKK1 gene promotor, thereby facilitating CaMKK1 expression and consequent activation of its downstream target CaMKIα, an essential regulator of spinogenesis. CaMKK1/CaMKIα signaling regulates actin cytoskeleton remodeling in the DH and behavioral plasticity by activation of Rac1 via acting Rac guanine-nucleotide-exchange factor ßPIX. These data suggest that Ube2b-dependent degradation of DNMT3a relieves a transcriptional brake on CaMKK1 gene and thus activates CaMKK1/CaMKIα/ßPIX/Rac1 cascade, leading to drug use-induced actin polymerization and behavior plasticity.

4.
Small ; : e1903522, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31608560

RESUMO

The CuS(x wt%)@Cu-BTC (BTC = 1,3,5-benzenetricarboxylate; x = 3, 10, 33, 58, 70, 99.9) materials are synthesized by a facile sulfidation reaction. The composites are composed of octahedral Cu3 (BTC)2 ·(H2 O)3 (Cu-BTC) with a large specific surface area and CuS with a high conductivity. The as-prepared CuS@Cu-BTC products are first applied as the anodes of lithium-ion batteries (LIBs). The synergistic effect between Cu-BTC and CuS components can not only accommodate the volume change and stress relaxation of electrodes but also facilitate the fast transport of Li ions. Thus, it can greatly suppress the transformation process from Li2 S to polysulfides by improving the reversibility of the conversion reaction. Benefiting from the unique structural features, the optimal CuS(70 wt%)@Cu-BTC sample exhibits a remarkably improved electrochemical performance, showing an over-theoretical capacity up to 1609 mAh g-1 after 200 cycles (100 mA g-1 ) with an excellent rate-capability of ≈490 mAh g-1 at 1000 mA g-1 . The outstanding LIB properties indicate that the CuS(70 wt%)@Cu-BTC sample is a highly desirable electrode material candidate for high-performance LIBs.

5.
Nat Commun ; 10(1): 4892, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653849

RESUMO

Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. Here, we report that genes involved in various human cancers evolved rapidly in Tibetans and six Tibetan domestic mammals compared to reciprocal lowlanders. Furthermore, m6A modified mRNA binding protein YTHDF1, one of evolutionary positively selected genes for high-altitude adaptation is amplified in various cancers, including non-small cell lung cancer (NSCLC). We show that YTHDF1 deficiency inhibits NSCLC cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. However, we observe that YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. Together, these findings highlight the critical role of YTHDF1 in both hypoxia adaptation and pathogenesis of NSCLC.

6.
Plant Cell Environ ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600410

RESUMO

Deep rooting is critical for access to water and nutrients found in subsoil. However, damage to soil structure and the natural increase in soil strength with depth, often impedes root penetration. Evidence suggests that roots use macropores (soil cavities greater than 75 µm) to bypass strong soil layers. If roots have to exploit structures, a key trait conferring deep rooting will be the ability to locate existing pore networks; a trait called trematotropism. In this study, artificial macropores were created in repacked soil columns at bulk densities of 1.6 g cm-3 and 1.2 g cm-3 , representing compact and loose soil. Near isogenic lines of wheat, Rht-B1a and Rht-B1c, were planted and root-macropore interactions were visualized and quantified using X-ray computed tomography. In compact soil, 68.8% of root-macropore interactions resulted in pore colonization, compared with 12.5% in loose soil. Changes in root growth trajectory following pore interaction were also quantified, with 21.0% of roots changing direction (±3°) in loose soil compared with 76.0% in compact soil. These results indicate that colonization of macropores is an important strategy of wheat roots in compacted subsoil. Management practices to reduce subsoil compaction and encourage macropore formation could offer significant advantage in helping wheat roots penetrate deeper into subsoil.

7.
PLoS One ; 14(10): e0222636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31593573

RESUMO

BACKGROUND: Escherichia coli is currently unable to be reliably differentiated from Shigella species by routine matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. In the present study, a reliable and rapid identification method was established for Escherichia coli and Shigella species based on a short-term high-lactose culture using MALDI-TOF MS and artificial neural networks (ANN). MATERIALS AND METHODS: The Escherichia coli and Shigella species colonies, treated with (Condition 1)/without (Condition 2) a short-term culture with an in-house developed high-lactose fluid medium, were prepared for MALDI-TOF MS assays. The MS spectra were acquired in linear positive mode, with a mass range from 2000 to 12000 Da and were then compared to discover new biomarkers for identification. Finally, MS spectra data sets 1 and 2, extracted from the two conditions, were used for ANN training to investigate the benefit on bacterial classification produced by the new biomarkers. RESULTS: Twenty-seven characteristic MS peaks from the Escherichia coli and Shigella species were summarized. Seven unreported MS peaks, with m/z 2330.745, m/z 2341.299, m/z 2371.581, m/z 2401.038, m/z 3794.851, m/z 3824.839 and m/z 3852.548, were discovered in only the spectra from the E. coli strains after a short-term high-lactose culture and were identified as belonging to acid shock protein. The prediction accuracies of the ANN models, based on data set 1 and 2, were 97.71±0.16% and 74.39±0.34% (n = 5), with an extremely remarkable difference (p < 0.001), and the areas under the curve of the receiver operating characteristic curve were 0.72 and 0.99, respectively. CONCLUSIONS: In summary, adding a short-term high-lactose culture approach before the analysis enabled a reliable and easy differentiation of Escherichia coli from the Shigella species using MALDI-TOF MS and ANN.

8.
Epigenetics Chromatin ; 12(1): 59, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594538

RESUMO

BACKGROUND: The stability of p53 is mainly controlled by ubiquitin-dependent degradation, which is triggered by the E3 ubiquitin ligase MDM2. The chromatin modifier lymphoid-specific helicase (LSH) is essential for DNA methylation and cancer progression as a transcriptional repressor. The potential interplay between chromatin modifiers and transcription factors remains largely unknown. RESULTS: Here, we present data suggesting that LSH regulates p53 in cis through two pathways: prevention proteasomal degradation through its deubiquitination, which is achieved by reducing the lysine 11-linked, lysine 48-linked polyubiquitin chains (K11 and K48) on p53; and revival of the transcriptional activity of p53 by forming a complex with PKM2 (pyruvate kinase 2). Furthermore, we confirmed that the LSH-PKM2 interaction occurred at the intersubunit interface region of the PKM2 C-terminal region and the coiled-coil domains (CC) and ATP-binding domains of LSH, and this interaction regulated p53-mediated transactivation in cis in lipid metabolism, especially lipid catabolism. CONCLUSION: These findings suggest that LSH is a novel regulator of p53 through the proteasomal pathway, thereby providing an alternative mechanism of p53 involvement in lipid metabolism in cancer.

9.
J Hazard Mater ; 384: 121277, 2019 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-31581018

RESUMO

In order to separate palladium (II) from electroplating wastewaters, poly(4-vinylpyridine)-b-polysulfone-b-poly(4-vinylpyridine) (P4VP-PSF-P4VP) / polysulfone blend membranes were fabricated by combining non-solvent induced phase separation, surface segregation and self-assembly of block copolymer. Amphiphilic P4VP-PSF-P4VP was used as the membrane base material, which was synthesized by introducing the functional monomer of 4-vinylpyridine (4-VP), and polysulfone as the additive. Effects of blend ratio and 4-VP content on membrane performance, such as structure, hydrophilicity, pure water flux and adsorption capacity towards Pd (II), were investigated. The membranes exhibited dense surface structure and low roughness due to surface segregation and self-assembly of P4VP-PSF-P4VP. The presence of 4-VP increased hydrophilicity and water flux of membrane, and it also provided good adsorption capacity towards Pd (II) (up to 103.1 ±â€¯5.15 mg/g). Further, the membrane was used to separate Pd (II) from simulated wastewaters during filtration. It showed good rejection ability and high selectivity towards Pd (II) in co-existence of Cu (II) and Ni (II), and selectivity coefficients of Pd/Cu and Pd/Ni are 41.9 ±â€¯1.88 and 97.8 ±â€¯4.32, respectively. In filtration process of actual electroplating wastewater, the membrane also exhibited excellent rejection performance (Pd (II) rejection reached up to 96.8 ±â€¯2.71%). Perhaps it is suitable for future practice applications.

10.
Cell Death Differ ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383984

RESUMO

Since publication of this article, the authors reported that the names of the corresponding authors had been placed in the wrong order.

11.
Oncogene ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31417184

RESUMO

Elucidating mechanisms in tumor suppressors and epigenetic modifiers are needed to gain insights into the etiology and treatment of cancer, the interplay between long intergenic non-coding RNAs (lncRNAs) and chromatin remodeling remains unclear. Here, we showed that GIAT4RA, a poorly characterized lncRNA LOC102723729, was significantly decreased in lung cancer cells and tissues; while no association was observed with clinical risk factors, expression was linked with clinical stage and lymphatic metastasis. Higher expression of GIAT4RA was linked with overall survival in NSCLC. GIAT4RA inhibited many characteristics of tumorigenesis including cell growth, clonal formation, migration and invasion, epithelial-mesenchymal transition, tumor sphere and tumor growth in vivo. Mechanistically, GIAT4RA was essential for the degradation of chromatin modifier lymphoid-specific helicase (LSH) by counteracting the deubiquintination in proteasome pathway by binding to 227-589 AA of LSH. GIAT4RA interfered with ubiquitin hydrolase Uchl3-mediated interaction and stabilization of LSH. LSH knockdown rescued GIAT4RA-promoted features, and LSH overexpression prevented GIAT4RA-induced phenotypes. Taken together, lncRNA GIAT4RA plays a critical role in NSCLC adenocarcinoma as a ubiquitination regulator and tumor suppressor.

12.
Cancer Res ; 79(17): 4387-4398, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31289136

RESUMO

Gastric cancer is the third leading cause of cancer-related death worldwide. The regulatory mechanisms underlying gastric cancer cell proliferation are largely unclear. Here, we show that the transcription factor GFI1 is associated with advanced clinical gastric cancer progression and promoted gastric cancer cell proliferation partially through inhibition of gastrokine-2 (GKN2) transcription. GFI1 was a degrading substrate of FBXW7, whose loss was observed in gastric cancer. Mechanistically, GSK3ß-mediated GFI1 S94/S98 phosphorylation triggered its interaction with FBXW7, resulting in SCFFBXW7-mediated ubiquitination and degradation. A nondegradable GFI1 S94A/S98A mutant was more potent in driving gastric cancer cell proliferation and tumorigenesis than wild-type GFI1. Overall, this study reveals the oncogenic role of GFI1 in gastric cancer and provides mechanistic insights into the tumor suppressor function of FBXW7. SIGNIFICANCE: These findings demonstrate the oncogenic role of the transcription factor GFI1 and the tumor suppressive function of FBXW7 in gastric cancer.

13.
Biochem Biophys Res Commun ; 516(1): 320-326, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31256935

RESUMO

Kappa-opioid receptor (KOR) is a member of G-protein coupled receptors (GPCRs) expressed in serotonergic neurons and neuronal terminals. The involvement of KOR ligands in nociception, diuresis, emotion, cognition, and immune system has been extensively studied. Omics-based methods are preferable to understand the signaling cascade after KOR activation in a systematic manner. In this study, an in-depth quantitative phosphoproteomic analysis resulted in 305 phosphosites, which were significantly changed in three KOR-overexpressed cells upon treatment with two KOR agonists. The subsequent substrate-kinase prediction analysis revealed that 18 potential kinases might be activated under stimulation of the agonists. We found that phosphorylation of PAK1/2 (p21-activated kinase 1/2) was induced by KOR agonists, resulting in reduced actin stress fibers and cytoskeletal reorganization. In summary, this quantitative phosphoproteomics-based research studied the downstream phosphorylation events upon KOR activation, which may shed light on the investigations of KOR signaling pathway and targeted therapy for KOR-related diseases.

14.
J Int Med Res ; : 300060519851651, 2019 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-31156003

RESUMO

Hydatidosis is a zoonotic parasitic disease caused by Echinococcus, which is highly prevalent in pastoral areas. In China, this disease is mainly caused by Echinococcus granulosus and Echinococcus multilocularis. Cystic echinococcosis, which is one of the most common types of echinococcosis, is described as swelling and growth of cystic lesions. Alveolar echinococcosis, which is less common, is invasive. Cases of mixed echinococcosis infection accompanied by extrahepatic organ metastasis are extremely rare. Treatment of these cases is complicated and the prognosis is extremely poor. We report a case of hepatic echinococcosis in a 40-year-old Tibetan man who was treated with the hepatic right tricuspidectomy + left hepatic duct jejunostomy (Roux-en-Y) surgical procedure. This procedure provides a reference for treatment of similar cases of echinococcosis. For patients with multiorgan metastasis, chemotherapy is the first choice. This should be followed by possible surgical treatment for life-threatening lesions of alveolar echinococcosis and subsequent chemotherapy. Individualized treatment accompanied by multidisciplinary treatment and damage control surgery could optimally benefit patients with advanced hepatic echinococcosis.

15.
Dalton Trans ; 48(28): 10661-10668, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31233051

RESUMO

ZIF-67 derived CoP-decorated nitrogen-doped porous carbon (CoP-NPC) polyhedra anchored on reduced graphene oxide (RGO) sheets have been successfully prepared through an efficient pyrolysis-phosphidation-assembly strategy. The resulting CoP-NPC/RGO composite as an electrode for supercapacitors shows an enhanced electrochemical performance with high capacitances of 466.6 F g-1 at 1 A g-1 and 252 F g-1 at 20 A g-1, as well as 94.7% of capacitance retention after 10 000 cycles in 1 M H2SO4 solution. Moreover, the symmetrical two-electrode device assembled from CoP-NPC/RGO electrodes delivers a high energy density of 12 W h kg-1 at a power density of 500 W kg-1 and excellent long-term cycling stability (93% of the initial capacitance after 10 000 cycles at 10 A g-1). This superior electrochemical performance of CoP-NPC/RGO can be ascribed to its 3D interconnected porous structure and the synergistic effect between CoP and the nitrogen-doped carbon matrix. The unique architecture of the composites can effectively enhance the electrochemical performance by shortening the diffusion distance of electrolyte ions and improving the electrical conductivity and the contact area between active materials and the electrolyte. The excellent electrochemical performances make CoP-NPC/RGO a promising electrode material for high-performance supercapacitors.

16.
iScience ; 15: 307-315, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31102996

RESUMO

Aryl-heteroatom (C-X) bonds ubiquitously exist in organic, medicinal, and material chemistry, but a universal method to construct diverse C-X bonds is lacking. Here we report our discovery of a convenient and efficient approach to construct various C-X bonds using arylammonium salts as the substrate via an SNAr process. This strategy features mild reaction condition, no request of transition metal catalyst, and easy formation of various C-X bonds (C-S, C-Si, C-Sn, C-Ge, C-Se, C-N). The method was successfully applied to a late-stage functionalization of an existing antibiotic drug, to a Clickable reaction of NBD-based ammonium salt as turn-on fluorescent probe to recognize L-cysteine and homocysteine, and to the synthesis of a DNA encoded library (DEL) bearing different C-X bonds.

18.
J Proteome Res ; 18(6): 2654-2665, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31059266

RESUMO

The deubiquitinase USP9X is involved in multiple diseases including neurodegeneration, epilepsy, and various types of tumors by targeting different substrates. In the present study, we aimed to explore the potential substrates of USP9X and performed SILAC-based quantitative proteomics to compare these substrates in USP9X-knockdown and wild-type HeLa cells. We consequently carried out Flag-NFX1-123 tag affinity-based mass spectrometry and confirmed that the X-box binding nuclear factor NFX1-123 interacted with USP9X. Moreover, immunoprecipitation assays verified a direct interaction between USP9X and NFX1-123. Further experiments confirmed that NFX1-123 could be modified by ubiquitination and that USP9X stabilized NFX1-123 via efficient deubiquitination of NFX1-123. Knockdown of USP9X resulted in decreased NFX1-123 protein levels compared with their unchanged corresponding mRNA levels in different cell lines. In summary, we found that NFX1-123 was a bona fide substrate of the deubiquitinase USP9X and that it could be degraded by the ubiquitin-proteasome system. The present study provided new insight into understanding the biological function of USP9X by targeting its substrate NFX1-123.

19.
Langmuir ; 35(22): 7285-7293, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31082261

RESUMO

The biomimetic membrane technology may unlock unprecedented membrane separation capabilities to solve the increasing need for clean water. Despite the efforts in exploring numerous membrane preparation methods, the membrane performance achieved to date is still far from the theoretical predictions. To overcome this bottleneck, a deeper understanding of the role of the channels or vesicles immobilized on the membrane would be required. In this work, we seek to quantify the amount of vesicles immobilized per unit area of membrane and correlate it with the membrane performance. The results show that, although the vesicles successfully immobilized onto the membrane increase with an increasing vesicle concentration, less than 4% of the vesicles loaded onto the membrane successfully remains on the membrane after interfacial polymerization. Furthermore, an increase in the amount of vesicles remaining on the membrane may not always result in improvement in membrane performance. To the best of our knowledge, this is the first time that a study has been performed to determine an accurate relationship between the vesicles immobilized and the biomimetic membrane performance.

20.
Cancer Cell ; 35(4): 677-691.e10, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991027

RESUMO

FTO, an mRNA N6-methyladenosine (m6A) demethylase, was reported to promote leukemogenesis. Using structure-based rational design, we have developed two promising FTO inhibitors, namely FB23 and FB23-2, which directly bind to FTO and selectively inhibit FTO's m6A demethylase activity. Mimicking FTO depletion, FB23-2 dramatically suppresses proliferation and promotes the differentiation/apoptosis of human acute myeloid leukemia (AML) cell line cells and primary blast AML cells in vitro. Moreover, FB23-2 significantly inhibits the progression of human AML cell lines and primary cells in xeno-transplanted mice. Collectively, our data suggest that FTO is a druggable target and that targeting FTO by small-molecule inhibitors holds potential to treat AML.

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