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1.
J Med Virol ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32056235

RESUMO

The outbreak of a novel coronavirus (SARS-CoV-2) since Dec 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS-CoV-2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS-CoV-2, SARS and MERS, highlighting the need for larger and well annotated datasets. This article is protected by copyright. All rights reserved.

2.
Small ; : e1906775, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31995284

RESUMO

Portable water splitting devices driven by rechargeable metal-air batteries or solar cells are promising, however, their scalable usages are still hindered by lack of suitable multifunctional electrocatalysts. Here, a highly efficient multifunctional electrocatalyst is demonstrated, i.e., 2D nanosheet array of Mo-doped NiCo2 O4 /Co5.47 N heterostructure deposited on nickel foam (Mo-NiCo2 O4 /Co5.47 N/NF). The successful doping of non-3d high-valence metal into a heterostructured nanosheet array, which is directly grown on a conductive substrate endows the resultant catalyst with balanced electronic structure, highly exposed active sites, and binder-free electrode architecture. As a result, the Mo-NiCo2 O4 /Co5.47 N/NF exhibits remarkable catalytic activity toward the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), affording high current densities of 50 mA cm-2 at low overpotentials of 310 mV for OER, and 170 mV for HER, respectively. Moreover, a low voltage of 1.56 V is achieved for the Mo-NiCo2 O4 /Co5.47 N/NF-based water splitting cell to reach 10 mA cm-2 . More importantly, a portable overall water splitting device is demonstrated through the integration of a water-splitting cell and two Zn-air batteries (open-circuit voltage of 1.43 V), which are all fabricated based on Mo-NiCo2 O4 /Co5.47 N/NF, demonstrating a low-cost way to generate fuel energy. This work offers an effective strategy to develop high-performance metal-doped heterostructured electrode.

3.
FASEB J ; 34(1): 1319-1330, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914610

RESUMO

Posttranslational modifications enhance the functional diversity of the proteome by modifying the substrates. The UFM1 cascade is a novel ubiquitin-like modification system. The mutations in UFM1, its E1 (UBA5) and E2 (UFC1), have been identified in patients with microcephaly. However, its pathological mechanisms remain unclear. Herein, we observed the disruption of the UFM1 cascade in Drosophila neuroblasts (NBs) decreased the number of NBs, leading to a smaller brain size. The lack of ufmylation in NBs resulted in an increased mitotic index and an extended G2/M phase, indicating a defect in mitotic progression. In addition, live imaging of the embryos revealed an impaired E3 ligase (Ufl1) function resulted in premature entry into mitosis and failed cellularization. Even worse, the embryonic lethality occurred as early as within the first few mitotic cycles following the depletion of Ufm1. Knockdown of ufmylation in the fixed embryos exhibited severe phenotypes, including detached centrosomes, defective microtubules, and DNA bridge. Furthermore, we observed that the UFM1 cascade could alter the level of phosphorylation on tyrosine-15 of CDK1 (pY15-CDK1), which is a negative regulator of the G2 to M transition. These findings yield unambiguous evidence suggesting that the UFM1 cascade is a microcephaly-causing factor that regulates the progression of the cell cycle at mitosis phase entry.

4.
Bioprocess Biosyst Eng ; 43(2): 273-282, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31595329

RESUMO

Structured lipids (SLs) rich in conjugated linoleic acid (CLA) and butyric acid with functions of low calorie and weight loss were synthesized in this study. By comparison of different synthetic routes, transesterification of CLA ethyl ester (CLAee) and tributyrin under vacuum was determined as the best method. The reaction conditions for SL synthesis were screened and the best conditions were as follows: Novozym 435 as the catalyst, enzyme load 6 wt%, temperature 60 °C, substrate molar ratio 2:1 (CLAee/tributyrin), water activity 0.68, reaction time 80 min. Under these conditions, the final product contained 97.5% of SLs, in which the contents of dibutyl-conjugated linoleoyl-glycerol and butyl-diconjugated linoleoyl-glycerol were 78.4% and 19.1%, respectively. The reusability evaluation indicated that the lipase could be reused at least 17 times. The obtained SLs with functions of both fatty acids could replace natural oil in food for inhibition of obesity and thus have great potential for commercial applications.

5.
Front Oncol ; 9: 1319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828041

RESUMO

Background: ALK and ROS1 rearrangement accounts for 3-6% and 1-3% of non-small cell lung cancers, respectively, while coexistence of them in the same patient is extremely rare. Only three cases have ever been reported with concurrent ALK/ROS1 fusions in the same tumor indicating tumor heterogeneity. Therefore, comprehensive genetic profiling via next-generation sequencing (NGS) is needed to provide fully molecular diagnosis. Case Presentation: A 50-year old Chinese female with resectable stage IB bilateral lung adenocarcinomas (ADCs) harbored EML4 exon 6-ALK exon 19 and TPM3 exon 8-ROS1 exon 35 fusions in the right lower and the left upper tumors, respectively, identified by clinical NGS test targeting 425 cancer-relevant genes. The results were further confirmed at RNA level using RNA-seq. Genomic evolution analysis reveals that these bilateral tumors are synchronous multiple primary lung cancers with no shared somatic alterations for both genes and arm-level copy number variations (CNVs). No recurrence was observed during 12 months of post-surgery follow-up. Conclusions: Our case is the first report of concurrent ALK/ROS1 fusions as distinct driver events of synchronous multiple primary lung cancers, and highlights the importance of individual genetic testing for each of the multiple primary tumors for fully molecular diagnosis and precise treatment decision-making.

6.
J Am Coll Cardiol ; 74(22): 2829-2830, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31779805
7.
Org Lett ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31411892

RESUMO

The first cobalt-catalyzed deaminative alkoxycarbonylation reaction was described for the conversion of readily available primary alkyl amines to synthetically versatile esters with moderate to high yields. This transformation shows good functional group compatibility and can serve as a powerful tool for the modification of alkyl amine-containing complex natural products and drug molecules.

8.
J Card Surg ; 34(10): 1088-1089, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31376177
9.
J Card Surg ; 34(10): 1090-1091, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31376179
10.
Nutr Cancer ; : 1-12, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31352802

RESUMO

Kudingcha is implicated in alleviating metabolic disorders in traditional Chinese medicine. However, the role of Kudingcha, one of the Ligustrum robustum species, in metabolic regulations and its antitumor activity in triple-negative breast cancer (TNBC) remains to be determined. Two breast cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Kudingcha treatment. The production of reactive oxygen species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift was examined by metabonomics and western blot analysis. In this study, we found that aqueous extract of Kudingcha dose dependently inhibited cell growth and induced apoptosis in vitro and in vivo. Moreover, Kudingcha supplementation significantly reduced cancer metastasis. Kudingcha significantly inhibited glycolysis and glutamine metabolism. In addition, we demonstrated that the antitumor effects of Kudingcha were dependent on ROS production, which was increased by ß-oxidation and oxidative phosphorylation. These findings provide a novel potential benefit of Kudingcha from targeting the cancer metabolism.

11.
Kidney Blood Press Res ; 44(4): 496-512, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256149

RESUMO

BACKGROUND: To evaluate the application of blood oxygenation level-dependent (BOLD)imaging and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) on assessing early contrast-induced acute kidney injury (CIAKI). MATERIALS: Sixty rabbits were randomly chosen to undergo iohexol (1.0, 2.5, and 5.0 [gI/kg], respectively; n = 15 for each group) or saline injection (n = 15). In each group, 6 rabbits underwent MRI at 24 h before injection and after injection of iohexol or saline (1 h and 1, 2, 3, and 4 days); meanwhile, out of the remaining 9 rabbits, 3 were chosen for MRI acquisition, and then they were killed at specific time points (1 h, 1 day, and 3 days, respectively). RESULTS: The strong attenuation of pure molecular diffusion (D), apparent diffusion coefficient (ADC), and perfusion fraction (f) was observed at 1 day, while pseudodiffusion coefficient (D*) showed a significant decrease at 1 h after iohexol injection. A distinct elevation of apparent transverse relaxation rate (R2*) reached the maximum levels on day 1, which was consistent with the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor. ADC, D, and R2* correlated well with histopathological parameters and biochemical parameters. CONCLUSION: BOLD combined with IVIM is effective to monitor renal pathophysiology associated with CIAKI.


Assuntos
Lesão Renal Aguda/diagnóstico por imagem , Meios de Contraste/efeitos adversos , Imagem por Ressonância Magnética/métodos , Oxigênio/sangue , Lesão Renal Aguda/induzido quimicamente , Animais , Imagem de Difusão por Ressonância Magnética/métodos , Modelos Animais de Doenças , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Coelhos , Ácidos Tri-Iodobenzoicos/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Cancer Manag Res ; 11: 4371-4390, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191001

RESUMO

Poly (ADP-ribose) polymerase (PARP) inhibitors are a class of targeted agents for the treatment of solid tumors. Concurrent PARP inhibition in Breast Cancer Susceptibility Gene (BRCA)-mutated or homologous recombination-deficient tumor cells can induce "synthetic lethality", which targets two DNA repair pathways and induces serious cytotoxicity to tumor cells without damaging normal cells. Currently, PARP inhibitors such as olaparib, rucaparib and niraparib, which improve progression-free survival, particularly in patients harboring BRCA mutations, are approved by the Food and Drug Administration (FDA) and European Medicine Agency (EMA) for the treatment of ovarian cancers. Based on the results of different clinical trials, the indications for these drugs are slightly different. PARP inhibitors have been studied both as single agents and in combination with chemotherapy, antiangiogenic agents, and ionizing radiation. This review summarizes the critical clinical trials of PARP inhibitors that have been completed, provides an overview of the ongoing trials, presents the confirmed conclusions and notes the issues that need to be addressed in future studies.

13.
Mol Brain ; 12(1): 52, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138234

RESUMO

Mushroom body (MB) is a prominent structure essential for olfactory learning and memory in the Drosophila brain. The development of the MB involves the appropriate guidance of axon lobes and sister axon branches. Appropriate guidance that accurately shapes MB development requires the integration of various guidance cues provided by a series of cell types, which guide axons to reach their final positions within the MB neuropils. Netrins are axonal guidance molecules that are conserved regulators of embryonic nerve cord patterning. However, whether they contribute to MB morphogenesis has not yet been evaluated. Here, we find that Netrin-B (NetB) is highly expressed in the MB lobes, regulating lobe length through genetic interactions with the receptors Frazzled and Uncoordinated-5 from 24 h after pupal formation onwards. We observe that overexpression of NetB causes severe ß lobe fusion in the MB, which is similar to the MB defects seen in the Drosophila model of fragile X syndrome (FXS). Our results further show that fragile-X mental retardation protein FMRP inhibits the translational activity of human ortholog Netrin-1 (NTN1). Knock-down of NetB significantly rescues the MB defects and ameliorates deficits in the learning and memory in FXS model Drosophila. These results indicate a critical role for NetB in MB lobe extension and identify NetB as a novel target of FMRP which contributes to learning and memory.

14.
Korean J Radiol ; 20(5): 830-843, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30993934

RESUMO

OBJECTIVE: To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model. MATERIALS AND METHODS: Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were calculated. RESULTS: The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels. CONCLUSION: A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney.


Assuntos
Lesão Renal Aguda/diagnóstico por imagem , Meios de Contraste/efeitos adversos , Diabetes Mellitus/patologia , Rim/diagnóstico por imagem , Imagem por Ressonância Magnética , Oxigênio/sangue , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/etiologia , Animais , Meios de Contraste/administração & dosagem , Meios de Contraste/química , Diabetes Mellitus/induzido quimicamente , Modelos Animais de Doenças , Hemodinâmica , Iodo/química , Rim/irrigação sanguínea , Rim/patologia , Masculino , Coelhos
15.
Biomed Pharmacother ; 115: 108884, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31035013

RESUMO

Breast cancer (BC) is the most common malignant tumor in women. Although overexpression of CD155 has been detected in many types of human cancer cells, it is not completely understood about its expression and function in BC and its prognostic significance. In the present study, we detected the expression level of CD155 in 216 cases of BC by immunohistochemistry (IHC), and we evaluated its relationship with BC patients' clinical information. We also analyzed the characteristics of CD163, CD8, and CD68 in 216 cases of BC patients through IHC. The results indicated that the CD155 expression level was significantly associated with primary tumor size (x2 = 23.593, P < 0.001), lymph node metastasis (x2 = 15.426, P < 0.001), tumour-node-metastasis (TNM) stage (x2 = 19.693, P < 0.001), Ki-67 (x2 = 9.355, P = 0.002), and CD163/CD8/CD68 expression on statistical analysis. BC patients with high expression of CD155 had poor overall survival rate, on both univariate analysis (Hazard ratio = 2.681, 95% CI = 1.458-4.928, P < 0.001) and multivariate analysis (Hazard ratio = 2.029, 95% CI = 1.059-3.887, P = 0.033). These results suggest an interaction between CD155 expression and tumor-infiltrating lymphocytes (TILs) in BC, and they also suggest that CD155 could be an effective prognostic biomarker for BC.


Assuntos
Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Receptores Virais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama/cirurgia , Feminino , Humanos , Linfócitos do Interstício Tumoral/fisiologia , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Receptores Virais/genética
16.
Biochem Biophys Res Commun ; 512(2): 196-201, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30879764

RESUMO

G-protein coupled receptor 120 (GPR120 or FFAR4) functions as a receptor for free fatty acids and plays a critical role in lipid metabolism. Studies have shown a close relationship between GDM and lipid metabolism disorders, whether GPR120 participates in the metabolic regulation of GDM remains unclear. In this study, 29 women with GDM and 33 normal pregnant women were enrolled. Lipid profiles were determined by lipidomics, expression of GPR120 and FGF21 was measured in the white blood cells, and regulation of FGF21 by GPR120 was investigated in THP-1 cells as well as human peripheral blood monocytes. Lipidomics reveal altered lipid metabolism in patients with GDM. The expression of both GPR120 and FGF21 is significantly higher in the GDM than in the control at the 32nd and 37th weeks of pregnancy, but the differences disappear by the 2nd day post-delivery. Generally positive correlations are found between the total amount of lipids and expression levels of GPR120 and FGF21 in GDM patients. FGF21 expression is induced by GPR120 activation in THP-1 cells and WBCs. GPR120 may act as a metabolic regulator, through the induction of FGF21, to control lipid metabolism, and GDM patients may manifest a GPR120 insensitivity.

17.
J Cell Mol Med ; 23(4): 2303-2313, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30672100

RESUMO

Poly (ADP-ribose) polymerase (PARP) inhibitors have provided great clinical benefits to ovarian cancer patients. To date, three PARP inhibitors, namely, olaparib, rucaparib and niraparib have been approved for the treatment of ovarian cancer in the United States. Homologous recombination deficiency (HRD) and platinum sensitivity are prospective biomarkers for predicting the response to PARP inhibitors in ovarian cancers. Preclinical data have focused on identifying the gene aberrations that might generate HRD and induce sensitivity to PARP inhibitors in vitro in cancer cell lines or in vivo in patient-derived xenografts. Clinical trials have focused on genomic scar analysis to identify biomarkers for predicting the response to PARP inhibitors. Additionally, researchers have aimed to investigate mechanisms of resistance to PARP inhibitors and strategies to overcome this resistance. Combining PARP inhibitors with HR pathway inhibitors to extend the utility of PARP inhibitors to BRCA-proficient tumours is increasingly foreseeable. Identifying the population of patients with the greatest potential benefit from PARP inhibitor therapy and the circumstances under which patients are no longer suited for PARP inhibitor therapy are important. Further studies are required in order to propose better strategies for overcoming resistance to PARP inhibitor therapy in ovarian cancers.

19.
Ther Hypothermia Temp Manag ; 9(2): 118-127, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30036167

RESUMO

Chipmunk as a food-storing hibernator naturally undergoes hibernation that is linked to great changes in systemic physiology and could protect the central nervous system during drastically reduced cerebral blood flow and low temperature in hibernation. Deep hypothermic circulatory arrest (DHCA) is associated with neurological dysfunction. We aim to test whether the euthermic chipmunk is resistant to injury from DHCA. Sprague-Dawley (SD) rats were used in a positive control. Ten euthermic chipmunks and 10 rats were subjected to 60-minute DHCA. Sham rats and chipmunks received cannulations. The blood samples after surgery were extracted to measure the tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) level. The levels of opioid receptor delta 1 (OPRD1), mature brain-derived neurotrophic factor (m-BDNF), precursor of BDNF (pro-BDNF), TrkB, GRB2, Erk, p-Erk, P38, Bcl-2, P75NTR, TRAF6, JNK, P53, Bax, and Caspase3 of the hippocampus were analyzed at 24 hours after surgery. The brain of chipmunks and rats were fixed for histopathological assessment. In the DHCA rat group, the levels of TNF-α and IL-6 were greater (p < 0.05) compared with DHCA chipmunks. In the DHCA chipmunk group, the levels of OPRD1, mature BDNF/pro-BDNF, TrkB-FL/TrkB-T1, Bcl-2, and p-Erk/Erk of hippocampus were higher than DHCA rats. The levels of GRB2, P75NTR, TRAF6, P53, Bax, and Caspase3 in DHCA chipmunks were lower than DHCA rats. The histopathological assessment showed that the injury in DHCA rat group was more severe than the DHCA chipmunk group. Euthermic chipmunks were greatly tolerant to global cerebral injury during DHCA. Different isoforms of BDNF might be involved in the resistant strategy.


Assuntos
Regulação da Temperatura Corporal , Lesões Encefálicas/prevenção & controle , Ponte Cardiopulmonar/efeitos adversos , Circulação Cerebrovascular , Parada Circulatória Induzida por Hipotermia Profunda/efeitos adversos , Hipocampo/irrigação sanguínea , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Mediadores da Inflamação/metabolismo , Masculino , Ratos Sprague-Dawley , Receptor trkB/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Sciuridae , Transdução de Sinais , Especificidade da Espécie
20.
Angew Chem Int Ed Engl ; 58(8): 2402-2406, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30565825

RESUMO

The palladium-catalyzed Heck reaction is a well-known, Nobel Prize winning transformation for producing alkenes. Unlike the alkenyl and aryl variants of the Heck reaction, the alkyl-Heck reaction is still underdeveloped owing to the competitive side reactions of alkyl-palladium species. Herein, we describe the development of a deaminative alkyl-Heck-type reaction that proceeds through C-N bond activation by visible-light photoredox catalysis. A variety of aliphatic primary amines were found to be efficient starting materials for this new process, affording the corresponding alkene products in good yields under mild reaction conditions. Moreover, this strategy was successfully applied to deaminative carbonylative alkyl-Heck-type reactions.

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