Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.039
Filtrar
Filtros adicionais











Intervalo de ano
1.
Mol Med Rep ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31485656

RESUMO

Microtubule­severing proteins (MTSPs) are a group of microtubule­associated proteins essential for multiple microtubule­related processes, including mitosis and meiosis. Katanin p60 ATPase­containing subunit A­like 1 (p60 katanin­like 1) is an MTSP that maintains the density of spindle microtubules at the poles in mitotic cells; however, to date, there have been no studies about its role in female meiosis. Using in vitro­matured (IVM) oocytes as a model, it was first revealed that p60 katanin­like 1 was predominant in the ovaries and oocytes, indicating its essential roles in oocyte meiosis. It was also revealed that p60 katanin­like 1 was concentrated at the spindle poles and co­localized and interacted with γ­tubulin, indicating that it may be involved in pole organization. Next, specific siRNA was used to deplete p60 katanin­like 1; the spindle organization was severely disrupted and characterized by an abnormal width:length ratio, multipolarity and extra aster microtubules out of the main spindles. Finally, it was determined that p60 katanin­like 1 knockdown retarded oocyte meiosis, reduced fertilization, and caused abnormal mitochondrial distribution. Collectively, these results indicated that p60 katanin­like 1 is essential for oocyte meiosis by ensuring the integrity of the spindle poles.

2.
BMC Public Health ; 19(1): 780, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31474224

RESUMO

BACKGROUND: With the changes in environmental, medical technique, population structure and national health projects, human mortality rates have undergone great changes all over the world. According to "World Health Statistics 2016: Monitoring Health for the SDGs (Sustainable Development Goals)", we can draw a globally vision about life expectancy and cause of death; also, significant inequality still persists within and among countries. This study was designed to research into the trend of mortality pattern in China, evaluate the disparities of age-specific and disease-specific mortality rates between male and female, and provides a scientific basis for further prevention strategies and policies design. METHODS: Data from the Chinese Disease Surveillance Points system were used to calculate crude and age-adjusted death rates, annual percent changes (APC) for men and women during 2004 to 2016. Age-standardized mortality rates (ASMR) were performed through the direct method with the World Health Organization's World Standard Population. APC, according to log linear model, was adopted to describe the mortality rate trend. The χ2 test was used to compare differences between age-specific and cause-specific mortality rates of men and women. Data analysis and figures were completed by R software. RESULTS: The mortality rates of men and women have decreased significantly (P < 0.05) during 2004-2016, and the APC were1.98 and 2.45%, respectively. In 2016, the crude mortality rate (CMR) and ASMR in all causes of death were 658.50 and 490.28 per 100,000 per year, respectively. The 5 leading causes of death were malignant neoplasm, cerebrovascular disease, heart disease, COPD, and accidental injury. The mortality rates of men were higher than that of women in all age groups. CONCLUSIONS: There are severe health gaps and disparities between male and female, and the chronic non-communicable diseases continue to be a serious health threat to Chinese residents.

3.
Phys Chem Chem Phys ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490519

RESUMO

Mg-M (M = Li, Na and K) dual-metal-ion batteries featuring a dendrite-free Mg anode and an alkali-metal-ion storage cathode are promising safe energy storage systems. However, the compatibility between cathode materials and insertion cations might largely limit the electrochemical performance of the cathodes. In this work, three types of Mg-M (M = Li, Na and K) dual-metal-ion batteries are constructed with a Berlin green (FeFe(CN)6) cathode. The FeFe(CN)6 cathode is compatible with the dual-salt Mg2+/M+ (M = Li, Na and K) electrolytes, and delivers a high reversible capacity of 120 mA h g-1 at 50 mA g-1, with no capacity fading over 50 cycles in Mg-Na batteries. The Mg-Na battery also shows an outstanding rate capability, providing 85 mA h g-1 at 1000 mA g-1 and superior long-term cyclability over 800 cycles. The electrochemical performance comparison between Mg-Li, Mg-Na and Mg-K dual-metal-ion batteries demonstrates the significance of the appropriate hydrated ionic radius and dehydrated ionic radius for the insertion of cations with the FeFe(CN)6 cathode. This work provides new design strategies for stable and high energy density cathodes, and opens a new avenue for building safe and high-performance Mg-M (M = Li, Na and K) dual-metal-ion batteries for practical applications.

4.
J Hematol Oncol ; 12(1): 91, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488218

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) have been associated with non-small cell lung cancer (NSCLC), but the underlying molecular mechanisms of their specific roles in mediating aerobic glycolysis have been poorly explored. METHODS: Next-generation RNA sequencing assay was performed to identify the differentially expressed RNAs between NSCLC tissues with high 18F-fluorodeoxyglucose (FDG) uptake and their adjacent normal lung tissues. LINC01123 expression in NSCLC tissues was measured by real-time PCR and in situ hybridization (ISH) assay. The biological role of LINC01123 in cell growth and aerobic glycolysis capability was determined by performing functional experiments in vitro and in vivo. Further, the transcription of LINC01123 was explored by bioinformatics analysis, dual-luciferase reporter assay, and chromatin immunoprecipitation (ChIP) assay. RNA immunoprecipitation (RIP) and luciferase analyses were used to confirm the predicted competitive endogenous RNA (ceRNA) mechanisms between LINC01123 and c-Myc. RESULTS: Three hundred sixty-four differentially expressed genes were identified in RNA-seq assay, and LINC01123 was one of the most overexpressed lncRNAs. Further validation in expanded NSCLC cohorts confirmed that LINC01123 was upregulated in 92 paired NSCLC tissues and associated with poor survival. Functional assays showed that LINC01123 promoted NSCLC cell proliferation and aerobic glycolysis. Mechanistic investigations revealed that LINC01123 was a direct transcriptional target of c-Myc. Meanwhile, LINC01123 increased c-Myc mRNA expression by sponging miR-199a-5p. In addition, rescue experiments showed that LINC01123 functioned as an oncogene depending on miR-199a-5p and c-Myc. CONCLUSION: Since LINC01123 is upregulated in NSCLC, correlates with prognosis, and controls proliferation and aerobic glycolysis by a positive feedback loop with c-Myc, it is expected to be a potential biomarker and therapeutic target for NSCLC.

5.
Int J Mol Sci ; 20(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514377

RESUMO

The lignin pyrolysis products generated by biomass combustion make an essential contribution to the formation of secondary organic aerosols (SOAs). The ozone-initiated oxidation of guaiacol, syringol and creosol, major constituents of biomass burning, were investigated theoretically by using the density functional theory (DFT) method at the MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p) level. Six primary addition reaction pathways and further decomposition routes with corresponding thermodynamic values were proposed. The Criegee intermediates can be excited by small molecules, such as NOx, H2O in the atmosphere, and would further proceed via self-decomposition or isomerization. The most predominant product for ozonation of guaiacol is the monomethyl muconate (P1). At 295 K and atmospheric pressure, the rate constant is 1.10 × 10-19 cm3 molecule-1 s-1, which is lies a factor of 4 smaller than the previous experimental study. The branching ratios of the six channels are calculated based on corresponding rate coefficient. The present work mainly provides a more comprehensive and detailed theoretical research on the ozonation of methoxyphenol, which aspires to offer novel insights and reference for future experimental and theoretical work and control techniques of SOAs caused by lignin pyrolysis products.

6.
Dalton Trans ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31508626

RESUMO

Rechargeable Mg batteries are promising candidates for highly safe, large-scale energy storage batteries due to the low-cost and non-dendritic metallic Mg anode. However, exploring high-performance cathodes remains a great challenge blocking their development. Herein, a rechargeable Mg battery is established with a Ag2S conversion cathode, providing a highly reversible capacity of 120 mA h g-1 at 50 mA g-1, a superior rate capability of 70 mA h g-1 at 500 mA g-1, and an outstanding long-term cyclability over 400 cycles. The mechanism was investigated using XRD, TEM and XPS in addition to electrochemical measurements, and indicated a two-stage magnesiation: first, Mg2+ intercalation into Ag2S and then a conversion reaction to form metallic Ag0 and MgS. The solid-state Mg2+ diffusion coefficients are as high as 3.6 × 10-9 and 3.1 × 10-10 cm2 s-1 for the intercalation and conversion reactions, respectively, which explains the high performance of the Ag2S cathode. This work provides scientific insights for the selection of a promising conversion cathode by the combination of soft anions and soft transition metal cations.

7.
Biomed Res Int ; 2019: 5763602, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31511824

RESUMO

Dioscin is a typical saponin with multiple pharmacological activities. The past few years have seen an emerging interest in and growing research on this pleiotropic saponin. Here, we review the emerging pharmacological activities reported recently, with foci on its antitumor, antimicrobial, anti-inflammatory, antioxidative, and tissue-protective properties. The potential use of dioscin in therapies of diverse clinical disorders is also discussed.

8.
J Orthop Surg Res ; 14(1): 290, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481082

RESUMO

PURPOSE: To evaluate the predictive effect of lumbar lordosis minus thoracic kyphosis (LL-TK) in the surgical outcome of adult degenerative scoliosis (ADS) patients and explore the optimum target base on it. METHODS: The preoperative and postoperative data including radiographic image and functional evaluation (Visual Analog Scale, VAS; Oswestry Disability Index, ODI; Japanese Orthopaedic Association, JOA) of 130 patients with ADS who underwent corrective surgery was retrospectively reviewed. The relationship between sagittal parameters and surgical outcome was assessed by using the Pearson correlation analysis. Receiver operating characteristic (ROC) curve was used to define the optimum cutoff value of LL-TK. Patients were divided into two groups based on LL-TK to compare the preoperative and postoperative status. RESULTS: LL-TK assessed soon after surgery strongly correlated with health-related quality of life (HRQOL) and sagittal vertical axis (SVA) at last follow-up. The cutoff value of LL-TK was set at 10° to determine a good clinical outcome (ODI < 20) and sagittal balance (SVA < 50 mm). Patients with LL-TK > 10° presented significantly better postoperative VAS, ODI, JOA, and SVA than patients with LL-TK < 10°. CONCLUSION: LL-TK could effectively predict postoperative HRQOL and sagittal balance for patients with ADS. Patients with LL-TK > 10° showed a better clinical outcome and sagittal balance, so LL-TK > 10° could be the optimum corrective target for these patients.

9.
J Cell Physiol ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506947

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a condition that results in the progressive deterioration of lung function with poor prognosis. The current study is aimed at exploring how microRNA-448 (miR-448) targeting ABCC3 affects fibroblast proliferation, apoptosis, and collagen synthesis of mice with IPF via the Jun N-terminal kinase (JNK) signaling pathway. Bioinformatics and dual-luciferase polymerase chain reaction were used to predict the relationship of miR-448 and ABCC3. The expression of miR-448 and ABCC3 was detected in IPF tissues. Using IPF mouse models, lung fibroblasts for the experiments were treated with miR-448 mimic, miR-448 inhibitor, si-ABCC3, or SP600125 (inhibitor of JNK) to evaluate the cell proliferation and apoptosis in response to miR-448. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to identify the expression of miR-448, ABCC3, and the activation of the JNK signaling pathway. ABCC3 was targeted and downregulated by miR-448 based on bioinformatics prediction and dual-luciferase reporter gene assay. Additionally, miR-448 was found to be highly expressed in IPF lung tissues with low expression levels of ABCC3. In response to the treatment of miR-448 mimic or si-ABCC3, lung fibroblasts exhibited decreased cell proliferation and increased apoptotic rates, whereas the miR-448 inhibitor reversed the conditions. Notably, we also found that miR-448 mimic inhibited the JNK signaling pathway. In conclusion, by using miR-448 to target and downregulate ABCC3 to block the JNK signaling pathway in mice with IPF, we found an increase in fibroblast apoptosis, inhibited cell proliferation, and decreased collagen synthesis of fibroblasts.

10.
Langmuir ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31502849

RESUMO

Development of high porous carbons with abundant surface functionalities and well-defined nanostructure is of significance for many important electrochemical energy storage systems. However, porous carbons suffer from a compromise between porosity, doped functionalities and nanostructure that has thus far restricted their performances. Here we report the design of highly porous, nitrogen-enriched hollow carbon nanospheres (PN-HCNs) by an interfacial copolymerization strategy followed by NH3-assisted carbonization, and further demonstrate their significance and effectiveness in enhancing the electrochemical performances. PN-HCN simultaneously delivers large surface area (1237 m2 g-1) and high N functionalities (6.25 at%) with a remarkable efficiency of surface area increase to N loss ratio enabled by NH3 treatment, and meanwhile inherits the hollow nanospherical structure. Accordingly, owing to the enhanced surface area and remained N doping, the prepared PN-HCN demonstrates outstanding electrochemical performances as host cathode in lithium-sulfur batteries, including a near-to-theoretical capacity of 1620 mAh g-1, high-rate capability, and good cycling stability (789 mAh g-1 at 0.5 C after 200 cycles). These results are superior to those of HCN without NH3 treatment. Also, PN-HCN exhibits superior capacitances (203 F g-1) and fast ion transport ability in supercapacitors. Our finding shows the simultaneous achievement of both highly porous structures and sufficient N functionalities towards high-performance applications.

11.
J Pain ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31494272

RESUMO

Orofacial pain is characterized by its easy spread to adjacent areas, thus presenting with primary hyperalgesia (hypersensitivity at the site of injury) and secondary hyperalgesia (extra-territorial hypersensitivity outside the injured zone). However, the mechanisms behind the secondary hyperalgesia are poorly understood. In the present study, we used a mouse model of partial transection of the infraorbital nerve (pT-ION) to study whether calcium channel subunit α2δ1 (Cavα2δ1) and its downstream signaling contributes to the development of secondary hyperalgesia in the orofacial area. pT-ION caused primary (V2 skin) and secondary (V3 skin) hyperalgesia, which was reversed by the Cavα2δ1 antagonist gabapentin and by the expression of Cavα2δ1-targeting interfering RNA in trigeminal ganglion (TG)-V3 neurons. pT-ION induced increased expression of PKC and TRPA1, which was reversed by Cavα2δ1-targeting interfering RNA, and PKC inhibition reversed the upregulation of TRPA1 and gap junction (GJ) proteins induced by pT-ION. Cavα2δ1 overexpression in TG-V2 neurons induced the upregulation of PKC, TRPA1, and the GJ proteins in the TG and trigeminal subnucleus caudalis and induced hypersensitivity in the V3 skin area, which was reversed by TRPA1, GJ, or PKC blockade. Thus, we conclude that Cavα2δ1 contributes to the development of secondary hyperalgesia through its downstream PKC-TRPA1/GJ signaling pathways. Perspective: This study demonstrates that the activation of Cavα2δ1 and the downstream PKC-TRPA1/GJ signaling pathway contributes greatly to trigeminal nerve injury-induced secondary mechanical and cold hyperalgesia. This suggests that inhibitors of Cavα2δ1, TRPA1, or GJs might be effective treatments for nerve injury-induced spreading of orofacial pain.

12.
Nanoscale ; 11(34): 16043-16051, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31432853

RESUMO

Rechargeable Mg batteries are promising candidates for highly safe large-scale energy storage batteries owing to their low-cost and non-dendritic metallic Mg anode. However, exploration of high-performance cathodes remains a great challenge hindering their development. Herein, a new pseudocapacitive Mg-storage nanowire material (a-MoS3@CNT) is constructed with a carbon nanotube (CNT) core and an amorphous MoS3 (a-MoS3) outer layer (15 nm thick). The nanowire cathode exhibits a high reversible capacity of 175 mA h g-1 at 100 mA g-1, a good rate performance of 50 mA h g-1 at 1000 mA g-1, and an outstanding long-term cyclability over 500 cycles. Further investigation of the mechanism demonstrates that the Mg-storage of a-MoS3@CNT is mainly achieved by the pseudocapacitance of a-MoS3, in which Mg2+ ions show fast solid-state diffusion kinetics. The present results demonstrate a new approach for efficient Mg-storage using pseudocapacitive materials, and the performance and solid-state Mg2+ diffusion kinetics could be optimized by delicate morphology tailoring.

13.
Obstet Gynecol ; 134(3): 511-519, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31403591

RESUMO

OBJECTIVE: To evaluate implementation of an enhanced recovery after surgery (ERAS) program for patients undergoing elective cesarean delivery by comparing opioid exposure, multimodal analgesia use, and other process and outcome measures before and after implementation. METHODS: An ERAS program was implemented among patients undergoing elective cesarean delivery in a large integrated health care delivery system. We conducted a pre-post study of ERAS implementation to compare changes in process and outcome measures during the 12 months before and 12 months after implementation. RESULTS: The study included 4,689 patients who underwent an elective cesarean delivery in the 12 months before (pilot sites: March 1, 2015-February 29, 2016, all other sites: October 1, 2015-September 30, 2016), and 4,624 patients in the 12 months after (pilot sites: April 1, 2016-March 31, 2017, all other sites: November 1, 2016-October 31, 2017) ERAS program implementation. After ERAS implementation mean inpatient opioid exposure (average daily morphine equivalents) decreased from 10.7 equivalents (95% CI 10.2-11.3) to 5.4 equivalents (95% CI 4.8-5.9) controlling for age, race-ethnicity, prepregnancy body mass index, patient reported pain score, and medical center. The use of multimodal analgesia (ie, acetaminophen and neuraxial anesthesia) increased from 9.7% to 88.8%, the adjusted risk ratio (RR) for meeting multimodal analgesic goals was 9.13 (RR comparing post-ERAS with pre-ERAS; 95% CI 8.35-10.0) and the proportion of time patients reported acceptable pain scores increased from 82.1% to 86.4% (P<.001). Outpatient opioids dispensed at hospital discharge decreased from 85.9% to 82.2% post-ERAS (P<.001) and the average number of dispensed pills decreased from 38 to 26 (P<.001). The hours to first postsurgical ambulation decreased by 2.7 hours (95% CI -3.1 to -2.4) and the hours to first postsurgical solid intake decreased by 11.1 hours (95% CI -11.5 to -10.7). There were no significant changes in hospital length of stay, surgical site infections, hospital readmissions, or breastfeeding rates. CONCLUSIONS: Implementation of an ERAS program in patients undergoing elective cesarean delivery was associated with a reduction in opioid inpatient and outpatient exposure and with changes in surgical process measures of care without worsened surgical outcomes.

14.
Oncologist ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434793

RESUMO

LESSONS LEARNED: Studies targeting the androgen receptor (AR) signaling pathway in aromatase inhibitor (AI)-resistant breast cancer are limited.Bicalutamide, one of the commonly used AR inhibitors in prostate cancer, in combination with AI, did not show synergistic activity in patients with estrogen receptor-positive and AI-resistant disease in this phase II, single-arm study.The clinical benefit rate and objective response rate at 6 months were 16.7% and 0%, respectively, and the study was terminated after the first stage. BACKGROUND: Endocrine resistance is a major problem in clinical practice. Studies have shown that androgen receptor (AR) signaling activation may be one of the mechanisms, and targeting AR showed some promising results in AR-positive triple-negative breast cancer. The aim of this study was to assess the efficacy and safety of bicalutamide plus another aromatase inhibitor in patients with nonsteroidal aromatase inhibitor (AI) or steroidal AI resistance and estrogen receptor (ER)-positive and AR-positive advanced breast cancer. METHODS: A Simon's two-stage, phase II, single-arm study was conducted. We assumed the clinical benefit rate (CBR) of 40% would be significant in clinical practice. In this case, if ≥4 patients of the 19 patients in the first stage benefited from treatment, the CBR would achieve the assumed endpoint. If fewer than four patients benefited from treatment in the first stage, the trial would be terminated. All patients received bicalutamide 50 mg per day orally plus another aromatase inhibitor. The primary outcome was CBR; secondary outcomes included objective response rate (ORR), progression-free survival (PFS), and tolerability. RESULTS: A total of 19 patients enrolled in the first stage, and 18 patients met all criteria for analysis. The trial terminated according to protocol after the first stage. After a median follow-up of 14 months, the CBR at 6 months was 16.7% (3/18); no patients with partial or complete response were observed. The median PFS was 2.7 months. Bicalutamide in combination with AI was well tolerated. CONCLUSION: Bicalutamide in combination with another AI did not show synergistic activity in patients with ER-positive breast cancer and AI resistance. Results suggest that no more large-sample clinical trials should be conducted in this population for overcoming endocrine resistance.

15.
Dev Psychol ; 55(9): 1830-1849, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31464489

RESUMO

In this article, we integrate two constructionist approaches-the theory of constructed emotion and rational constructivism-to introduce several novel hypotheses for understanding emotional development. We first discuss the hypothesis that emotion categories are abstract and conceptual, whose instances share a goal-based function in a particular context but are highly variable in their affective, physical, and perceptual features. Next, we discuss the possibility that emotional development is the process of developing emotion concepts, and that emotion words may be a critical part of this process. We hypothesize that infants and children learn emotion categories the way they learn other abstract conceptual categories-by observing others use the same emotion word to label highly variable events. Finally, we hypothesize that emotional development can be understood as a concept construction problem: a child becomes capable of experiencing and perceiving emotion only when her brain develops the capacity to assemble ad hoc, situated emotion concepts for the purposes of guiding behavior and giving meaning to sensory inputs. Specifically, we offer a predictive processing account of emotional development. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

16.
Front Immunol ; 10: 1826, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417578

RESUMO

IκB kinases (IKKs) play critical roles in innate immunity through signal-induced activation of the key transcription factors nuclear factor-κB (NF-κB) and interferon regulatory factors (IRFs). However, studies of invertebrate IKK functions remain scarce. In this study, we performed phylogenetic analysis of IKKs and IKK-related kinases encoded in the Pacific oyster genome. We then cloned and characterized the oyster IKKα/ß-2 gene. We found that oyster IKKα/ß-2, a homolog of human IKKα/IKKß, responded to challenge with lipopolysaccharide (LPS), peptidoglycan (PGN), and polyinosinic-polycytidylic acid [poly(I:C)]. As a versatile immune molecule, IKKα/ß-2 activated the promoters of NF-κB, TNFα, and IFNß, as well as IFN-stimulated response element (ISRE)-containing promoters, initiating an antibacterial or antiviral immune state in mammalian cells. Importantly, together with the cloned oyster IKKα/ß-1, we investigated the signal transduction pathways mediated by these two IKKα/ß proteins. Our results showed that IKKα/ß-1 and IKKα/ß-2 could interact with the oyster TNF receptor-associated factor 6 (TRAF6) and that IKKα/ß-2 could also bind to the oyster myeloid differentiation factor 88 (MyD88) protein directly, suggesting that oyster IKKα/ßs participate in both RIG-I-like receptor (RLR) and Toll-like receptor (TLR) signaling for the reception of upstream immune signals. The fact that IKKα/ß-1 and IKKα/ß-2 formed homodimers by interacting with themselves and heterodimers by interacting with each other, along with the fact that both oyster IKKα/ß proteins interacted with NEMO protein, indicates that oyster IKKα/ßs and the scaffold protein NEMO form an IKK complex, which may be a key step in phosphorylating IκB proteins and activating NF-κB. Moreover, we found that oyster IKKα/ßs could interact with IRF8, and this may be related to the IKK-mediated activation of ISRE promotors and their involvement in the oyster "interferon (IFN)-like" antiviral pathway. Moreover, the expression of oyster IKKα/ß-1 and IKKα/ß-2 may induce the phosphorylation of IκB proteins to activate NF-κB. These results reveal the immune function of oyster IKKα/ß-2 and establish the existence of mollusk TLR and RLR signaling mediated by IKKα/ß proteins for the first time. Our findings should be helpful in deciphering the immune mechanisms of invertebrates and understanding the development of the vertebrate innate immunity network.

17.
J Med Chem ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31408335

RESUMO

We unveiled an underside binding site on smoothened receptor (SMO) by a co-localization strategy using two struc-turally-complementary photoaffinity probes, derived from a known ligand Allo-1. Docking study and structural dissec-tion identified key interactions within the site, including hydrogen bonding, π-π interactions, and hydrophobic inter-actions between Allo-1 and its contacting residues. Taken together, our results reveal the molecular base of Allo-1 binding and provide a basis for the design of new-generation ligands to overcome drug resistance.

18.
Metab Brain Dis ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31410775

RESUMO

Schizophrenia is a kind of neurodevelopmental disease. Epidemiological data associates schizophrenia with prenatal exposure to famine. Relevant prenatal protein deprivation (PPD) rodent models support this result by observing decreasing prepulse inhibition, altered hippocampal morphology and impaired memory in offspring. All these abnormalities are highly consistent with the pathophysiology of schizophrenia. We developed a prenatal famine rat model by restricting daily diet of the pregnant rat to 50% of low protein diet. A metabolomics study of prefrontal cortex was performed to integrate GC-TOFMS and UPLC-QTOFMS. Thirteen controls and thirteen famine offspring were used to differentiate in PLS-DA (partial least squares-discriminate analysis) model. Furthermore, metabolic pathways and diseases were enriched via KEGG and HMDB databases, respectively. A total of 67 important metabolites were screened out according to the multivariate analysis. Schizophrenia was the most statistical significant disease (P = 0.0016) in our famine model. These metabolites were enriched in key metabolic pathways related to energy metabolism and glutamate metabolism. Based on these important metabolites, further discussion speculated famine group was characterized by higher level of oxidized damage compared to control group. We proposed that oxidative stress might be the pathogenesis of prenatal undernutrition which is induced schizophrenia.

19.
Molecules ; 24(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370187

RESUMO

This paper compares the differences in metabolites of vanilla beans at five different curing stages. Key vanilla flavors, vanillin precursors and main enzymes during the curing process of Hainan vanilla beans were also analyzed. Hundreds of metabolites were detected based on metabolic analyses of a widely targeted metabolome technique, compared with blanched vanilla beans (BVB), sweating vanilla beans (SVB) and drying vanilla beans (DVB), the total peak intensity of cured vanilla beans (CVB) is on the rise. The score plots of principal component analysis indicated that the metabolites were generally similar at the same curing stages, but for the different curing stages, they varied substantially. During processing, vanillin content increased while glucovanillin content decreased, and vanillic acid was present in sweating beans, but its content was reduced in drying beans. Both p-hydroxybenzaldehyde and p-hydroxybenzoic acid showed the maximum contents in cured beans. Ferulic acid was mainly produced in drying beans and reduced in cured beans. p-coumaric acid increased during the curing process. Vanillyl alcohol in drying beans (0.22%) may be formed by the hydrolysis of glucoside, whose conversion into vanillin may explain its decrease during the curing stage. ß-Glucosidase enzymatic activity was not detected in blanched and sweating beans, but was observed after drying. Peroxidase activity decreased during curing by 94% in cured beans. Polyphenol oxidase activity was low in earlier stages, whereas cellulase activity in processed beans was higher than in green beans, except for cured beans. This study contributes to revealing the formation of flavor components and the biosynthesis pathway of vanillin.

20.
Genet Test Mol Biomarkers ; 23(8): 589-597, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31373849

RESUMO

Objectives: Anaplastic lymphoma kinase (ALK) is one of the leading therapeutic targets in patients with non-small cell lung cancer (NSCLC). However, the clinical importance that the percentage of ALK-positive tumor cells has on NSCLC remains unclear. Methods: A total of 344 ALK-positive patients were enrolled in this study. The percentage of ALK-positive tumor cells was identified by fluorescence in situ hybridization. The discrimination and calibration analyses of the nomogram were estimated with Harrell's C-index. Results: Higher percentages (≥50%) of ALK-positive tumor cells were significantly correlated with male gender, poor differentiation, and normal levels of carbohydrate antigen 153 (CA153) and blood platelets (p < 0.05). A shorter first-line progression-free survival (PFS) was correlated with a lower percentage (15-49%) of ALK-positive tumor cells, chemotherapy, a poor performance state, non-adenocarcinoma, as well as abnormal CA153 and Cyfra21-1 levels; and an abnormal thrombin time (p < 0.05). A low percentage of ALK-positive tumor cells, crizotinib treatment, CA153 levels, and neutrophil count were independent risk factors for poor PFS in the multivariate analysis (p < 0.05). The nomogram showed a C-index of 0.76 for first-line PFS. Conclusion: A nomogram including the percentage of ALK-positive tumor cells may act as a crucial indicator for first-line PFS in ALK-positive NSCLC patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA