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1.
Phytochemistry ; 171: 112228, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911265

RESUMO

A previously undescribed taraxerene-type triterpenoid possessing a class of rare natural taraxerene triterpenoid possessing skeleton with 14, 28-lactone, two undescribed oleane-type triterpenoids, and twenty-five known triterpenoids were isolated from Liquidambar formosana (Hamamelidaceae). The structures of undescribed compounds were determined on the basis of 1D and 2D NMR spectroscopic, HR-ESI-MS, and X-ray crystallographic data analysis. Among the isolates, ursolic acid, 3,6-dion-20(29)-lupen-28-oic acid, and 3-oxo-12α-hydroxyoleanan-28,13ß-olide induced a significant apoptosis in SMMC7721 cells in the flow cytometer experiment with apoptosis rates of 94.5%, 57.3% and 89.9% at 8.0 µM, respectively, exhibiting near equivalent apoptosis-inducing abilities to that positive drug taxol (apoptotic rate of 71.2% at 1.4 µM). Mechanism studies suggested that these three compounds could regulate the mitochondrial pathway by up-regulating the expressions of pro-apoptotic factors (Bad and Bax) and activating caspase-3 and caspase-9 to induce apoptosis. Further studies indicated that the pro-apoptotic effects of these three compounds were associated with PI3K-AKT pathway inhibition. Taken together, these studies provide evidence that triterpenoids from L. Fructus are promising candidates for the hepatocellular carcinoma therapy.

2.
Phytochemistry ; 171: 112233, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911267

RESUMO

Eight previously undescribed and 15 known components, including six neolignans, two monolignan, three sesquineolignans, three dineolignans, eight phenylpropanoids, and one steroid were identified from the seed testa of Vernicia fordii. Their structures were established based on the comprehensive analysis of NMR and ECD data. The anti-neuroinflammatory effects of the isolates were evaluated through nitrite assays in LPS-induced BV2 cells. As a result, isodiverniciasin A, diverniciasin B, diverniciasin C, isoprincepin, princepin, 3, 3'-bisdemethylpinoresinol, (+)-7-epi-sesamin-dicatechol, isoamericanin A, americanin B, 7S, 8R-americanin D, 4-hydroxyl cinnamic aldehyde, 3-hydroxyl-4-methoxyl cinnamic aldehyde and 24R-6ß-hydroxy-24- ethylcholest-4-en-3-one exhibited significant inhibitory effects on nitric oxide (NO) production and isoprincepin, princepin, americanin B, and 4-hydroxyl cinnamic aldehyde suppressed the overexpression of inflammatory cytokines TNF-α, IL-1ß, and IL-6 in over-activated microglia. The results suggested that bioactive ingredients from the seed testa of V. fordii can serve as potential therapeutic agents for neurodegenerative diseases.

3.
Science ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919128

RESUMO

Materials with high thermal conductivity (κ) are of technological importance and fundamental interest. We grew cubic boron nitride (cBN) crystals with controlled abundance of boron isotopes and measured κ over 1600 Wm-1 K-1 at room temperature in samples with enriched 10B or 11B. In comparison, we found the isotope enhancement of κ is considerably lower for boron phosphide and boron arsenide as the identical isotopic mass disorder becomes increasingly invisible to phonons. The ultrahigh κ in conjunction with its wide bandgap (6.2 eV) makes cBN a promising material for microelectronics thermal management, high-power electronics, and optoelectronics applications.

4.
J Am Chem Soc ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31922412

RESUMO

Most organic piezochromic materials exhibit red-shifted and quenched emission as pressure increases. However, an ab-normal phenomenon of pressure-induced blue-shifted and enhanced emission is observed in a 9-(3-(1,2,2-triphenylvinyl)phenyl)anthracene crystal, which is based on discrete π-π anthracene (AN) dimer stacking with tetra-phenyl ethylene (TPE) as a spacer. A blue-shifted emission appears and strengthens when pressure is more than 1.23 GPa, and it reaches the maximum when pressure is 4.28 GPa. This phenomenon is ascribed to the cooperative effect be-tween the aggregation-induced emission of TPE units and energy-transfer suppression from TPE to an AN excimer. This work reports a new concept in the piezochromic field and provides a novel strategy to achieve luminescence from a high-lying excited state.

5.
BMC Med Genomics ; 13(1): 3, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906958

RESUMO

BACKGROUND: MiR-182-5p, a cancer-related microRNA (miRNA), modulates tumorigenesis and patient outcomes in various human malignances. This study interroted the clinicopathological significance and molecular mechanisms of miR-182-5p in non-small cell lung cancer (NSCLC). METHODS: The clinical significance of miR-182-5p in NSCLC subtypes was determined based on an analysis of 124 samples (lung adenocarcinomas [LUADs], n = 101; lung squamous cell carcinomas [LUSCs], n = 23) obtained from NSCLC patients and paired noncancer tissues and an analysis of data obtained from public miRNA-seq database, miRNA-chip database, and the scientific literature. The NSCLC samples (n = 124) were analyzed using the real-time quantitative polymerase chain reaction (RT-qPCR). Potential targets of miR-182-5p were identified using lists generated by miRWalk v.2.0, a comprehensive atlas of predicted and validated targets of miRNA-target interactions. Molecular events of miR-182-5p in NSCLC were unveiled based on a functional analysis of candidate targets. The association of miR-182-5p with one of the candidate target genes, homeobox A9 (HOXA9), was validated using in-house RT-qPCR and dual-luciferase reporter assays. RESULTS: The results of the in-house RT-qPCR assays analysis of data obtained from public miRNA-seq databases, miRNA-chip databases, and the scientific literature all supported upregulation of the expression level of miR-182-5p level in NSCLC. Moreover, the in-house RT-qPCR data supported the influence of upregulated miR-182-5p on malignant progression of NSCLC. In total, 774 prospective targets of miR-182-5p were identified. These targets were mainly clustered in pathways associated with biological processes, such as axonogenesis, axonal development, and Ras protein signal transduction, as well as pathways involved in axonal guidance, melanogenesis, and longevity regulation, in multiple species. Correlation analysis of the in-house RT-qPCR data and dual-luciferase reporter assays confirmed that HOXA9 was a direct target of miR-182-5p in NSCLC. CONCLUSIONS: The miR-182-5p expression level was upregulated in NSCLC tissues. MiR-182-5p may exert oncogenic influence on NSCLC through regulating target genes such as HOXA9.

6.
Transl Stroke Res ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907728

RESUMO

Blood-brain barrier (BBB) disruption is one of the critical mechanisms of brain injury induced by subarachnoid hemorrhage (SAH). Past studies have often focused on the tight junctions of endothelial cells. However, low transcellular transport levels also play an important role in the normal functioning of the BBB. Major facilitator superfamily domain-containing 2a (Mfsd2a) has been demonstrated to be essential for the maintenance of the normal BBB. Our present study aimed to explore the roles and mechanisms of Mfsd2a in BBB disruption after SAH. In this study, a prechiasmatic cistern single-injection model was used to produce experimental SAH in Sprague-Dawley rats. Specific small-interfering RNA and plasmids were used to downregulate and upregulate the expression of Mfsd2a prior to assessments in our SAH model. Omega-3 fatty acid deficiency diet was used to reduce DHA in rat brain. The expression level of Mfsd2a decreased significantly after SAH and reached its lowest level at 72 h post-SAH, which then gradually recovered. At 72 h after SAH, BBB function was disrupted; upregulation of Mfsd2a reversed this damage, whereas downregulation of Mfsd2a exacerbated this damage. These effects were primarily mediated through transcellular transport, especially for changes in caveolae compared to those of tight junctions. After stopping the supply of omega-3 fatty acids, the effect of Mfsd2a on inhibition of caveolae and protection of the blood-brain barrier was eliminated. Taken together, Mfsd2a inhibits caveolae-based transcellular transport by transporting omega-3 fatty acids to protect the BBB after SAH.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31916741

RESUMO

The development of high-performance electrode materials is of great significance for the next generation room temperature sodium-ion batteries. In this work, a new Na super-ionic conductor (NASICON) negative electrode, AgTi2(PO4)3, is prepared by a facile solid-state reaction and employed as sodium storage material for the first time. In situ X-ray diffraction during battery operation reveals an electrochemically Ag nanoparticle coating mechanism upon sodiation, facilitating the electron transfer in the complex. In addition, two steps of highly reversible biphasic transformation are observed. As a result, a reversible capacity of 214.9 mA h g-1 can be achieved, corresponding to the insertion/extraction of nearly four sodium ions. The AgTi2(PO4)3 electrode also demonstrates better kinetic properties than bare NaTi2(PO4)3 material. Such an "in situ" decorating method can open up a new direction for the design of NASICON-structured materials.

8.
Colorectal Dis ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31925981

RESUMO

Anastomotic leak is one of the common and serious complications after laparoscopic rectal cancer excision. Anastomotic leak not only causes abdominal infection and endangers life, but also promotes local recurrence of tumour. So, prevention of anastomotic leak is very important. Most surgeons like to perform an air test when the anastomosis is completed.

9.
Proc Natl Acad Sci U S A ; 117(1): 292-299, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31879340

RESUMO

We describe a Kappa-on-Heavy (KoH) mouse that produces a class of highly diverse, fully human, antibody-like agents. This mouse was made by replacing the germline variable sequences of both the Ig heavy-chain (IgH) and Ig kappa (IgK) loci with the human IgK germline variable sequences, producing antibody-like molecules with an antigen binding site made up of 2 kappa variable domains. These molecules, named KoH bodies, structurally mimic naturally existing Bence-Jones light-chain dimers in their variable domains and remain wild-type in their antibody constant domains. Unlike artificially diversified, nonimmunoglobulin alternative scaffolds (e.g., DARPins), KoH bodies consist of a configuration of normal Ig scaffolds that undergo natural diversification in B cells. Monoclonal KoH bodies have properties similar to those of conventional antibodies but exhibit an enhanced ability to bind small molecules such as the endogenous cardiotonic steroid marinobufagenin (MBG) and nicotine. A comparison of crystal structures of MBG bound to a KoH Fab versus a conventional Fab showed that the KoH body has a much deeper binding pocket, allowing MBG to be held 4 Å further down into the combining site between the 2 variable domains.

10.
Drug Metab Dispos ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836608

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are potent carcinogens and are a primary risk factor in the development of lung and other aerodigestive tract cancers in smokers. The detoxification of PAHs by glucuronidation is well-characterized for the UDP-glycosyltransferase (UGT) 1A, 2A, and 2B subfamilies; however, the role of the UGT3A subfamily in PAH metabolism remains poorly understood. UGT3A enzymes are functionally distinct from other UGT subfamilies (which utilize UDP-glucuronic acid as cosubstrate) due to their utilization of alternative cosubstrates (UDP-N-acetylglucosamine for UGT3A1, and UDP-glucose and UDP-xylose for UGT3A2). The goal of the present study was to characterize UGT3A glycosylation activity against PAHs and examine their expression in human aerodigestive tract tissues. In vitro metabolism assays using UGT3A2-overexpressing cell microsomes indicated that UGT3A2 exhibits glycosylation activity against all of the simple and complex PAHs tested. The Vmax/Km ratios for UGT3A2 activity with UDP-xylose vs. UDP-glucose as cosubstrate ranged from 0.71-4.0 for all PAHs tested, demonstrating that PAH glycosylation may be occurring at rates up to four-fold higher with UDP-xylose than UDP-glucose. Limited glycosylation activity was observed against PAHs with UGT3A1-overexpressing cell microsomes. While UGT3A2 exhibited low levels of hepatic expression, it was shown by Western blot analysis to be widely expressed in aerodigestive tract tissues. Conversely, UGT3A1 exhibited highest expression in liver with lower expression in aerodigestive tract tissues. These data suggest that UGT3A2 plays an important role in the detoxification of PAHs in aerodigestive tract tissues, and that there may be cosubstrate dependent differences in the detoxification of PAHs by UGT3A2. SIGNIFICANCE STATEMENT: UGT3A2 is highly active against PAHs with either UDP-glucose or UDP-xylose as a cosubstrate. UGT3A1 exhibited low levels of activity against PAHs. UGT3A1 is highly expressed in liver while UGT3A2 is well-expressed in extra-hepatic tissues. UGT3A2 may be an important detoxifier of PAHs in humans.

12.
Int Immunopharmacol ; : 106000, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31806569

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) playing crucial roles in sepsis-induced diseases, including myocardial inflammation. Nevertheless, the expression pattern and role of miR-215-5p in myocardial inflammation are still un-investigated up to now. The purpose of our study is to further inquire the effect of miR-215-5p on lipopolysaccharide (LPS)-activated inflammation injury in H9c2 cells and the possibly associated mechanisms. First of all, LPS-induced H9c2 cells models were constructed and affirmed via detection of pro-inflammatory factors, the viability and apoptosis. MiR-215-5p was overtly down-regulated in LPS-treated H9c2 cells and miR-215-5p overexpression could suppress the inflammation injury. LRRFIP1 was proved to be the target gene of miR-215-5p and meanwhile, miR-215-5p also targeted ILF3 that experimented to bind to and stabilize LRRFIP1. Final rescue assays confirmed that the overexpression of LRRFIP1 or ILF3 rescued the repressive effect of miR-215-5p up-regulation on the inflammation injury in septic H9c2. Totally, miR-215-5p exerted protective function in the inflammation injury in septic H9c2 via targeting ILF3 and LRRFIP1, suggesting an additional treatment method for sepsis-activated myocardial inflammation.

13.
J Integr Plant Biol ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829514

RESUMO

Flowering time regulation is one of the most important processes in the whole life of flowering plants and FLC is a central repressor of flowering time. However whether metabolic acetate level affects flowering time is unknown. Here we report that ALDEHYDE DEHYDROGENASE ALDH3F1 plays essential roles in floral transition via FLC-dependent pathway. In the aldh3f1-1 mutant, the flowering time was significant earlier than Col-0 and the FLC expression level was reduced. ALDH3F1 had aldehyde dehydrogenase activity to affect the acetate level in plants, and the amino acids of E214 and C252 are essential for its catalytic activity. Moreover, aldh3f1 mutation reduced acetate level and the total acetylation on histone H3. The H3K9Ac level on FLC locus was decreased in aldh3f1-1, which reduced FLC expression. Expression of ALDH3F1 could rescue the decreased H3K9Ac level on FLC, FLC expression and also the early-flowering phenotype of aldh3f1-1, however ALDH3F1E214A or ALDH3F1C252A could not. Our findings demonstrate that ALDH3F1 participates in flowering time regulation through modulating the supply of acetate for acetyl-CoA, which functions as histone acetylation donor to modulate H3K9Ac on FLC locus. This article is protected by copyright. All rights reserved.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31829546

RESUMO

A novel metallic carbon allotrope, Q-carbon, was discovered using first-principles calculations. The named Q-carbon possessed a three-dimensional (3D) cage structure formed by carbon atoms with three ligands. The energy distribution of electrons in different orbitals revealed that Q-carbon has low degree of s-p orbital hybridization. The calculated Li+ binding energies suggested Li+ aggregation inside Q-carbon during lithiation. As a result, a Li8C32 phase was formed and gradually expanded in Q-carbon, implying a typical two-phase transition. This allowed Q-carbon to have a constant theoretical voltage of 0.40 V, which effectively inhibited Li dendrite formation. Stable Li8C32/C32 two-phase interface was confirmed by a stress-strain analysis and the calculated Li+ diffusion barrier of ~0.50 eV ensured effective Li+ diffusion along a 3D pathway. This study was of great significance for the understanding of two-phase transition of Li+ storage materials and provided a new insight into the design of new carbon materials for energy storage applications.

15.
Sci Prog ; : 36850419874201, 2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31829869

RESUMO

Strain gage sensors have been used to evaluate the local behavior of structures; however, there are limited studies for its application in bridge dynamic feature identification. In this study, fiber Bragg grating strain gages were installed on the lower chord members of a bridge, and dynamic features were identified successfully using strain gage readings when vehicles passed over the bridge. The results were also verified using a finite element model. The innovation presented in this article is the use of fiber Bragg grating strain gage readings to identify the dynamic features of a long-span, steel-girder bridge. To clarify the effect of truck dynamic load, the load spectrum of the truck is characterized. This article introduces a new method for identifying the dynamic parameters of bridges.

16.
Nanomaterials (Basel) ; 9(12)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31817378

RESUMO

As an energy-efficient surface modification method, self-assembly has been the subject of extensive research. However, its application on carbon film has been rarely reported. In the present work, a novel self-assembled reduced graphene oxide (RGO) was prepared on a-C:H film by a controllable self-assembly method, and the friction behavior of the RGO/a-C:H film was investigated under vacuum environment. Interestingly, the RGO/a-C:H film exhibited significant improvement of anti-wear ability in vacuum conditions under a high applied load of 5 N. As expected, the synergy lubrication effect of the RGO layer and a-C:H film should account for the excellent friction reduction and anti-wear ability of a RGO/a-C:H multilayer film.

17.
Onco Targets Ther ; 12: 9827-9848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819482

RESUMO

Introduction: MIR22HG has a reported involvement in the tumorigenesis of a variety of cancers, including hepatocellular carcinoma (HCC). However, the exact molecular mechanism of MIR22HG in HCC has not been clarified. Methods: In the present study, we integrated data from in-house RT-qPCR, RNA-sequencing, microarray, and literature studies to conduct a comprehensive evaluation of the clinico-pathological and prognostic significance of MIR22HG in an extremely large group of HCC samples. We also explored the potential mechanism of MIR22HG in HCC by analyzing the alteration profiles of MIR22HG in HCC to predict transcription factors (TFs) that may interact with MIR22HG and to annotate the biological functions of genes co-expressed with MIR22HG. MIR22HG expression was also compared in HCC nude mice xenografts before and after a treatment with nitidine chloride. Results: We found that MIR22HG was downregulated in HCC and that this downregulation correlated with the malignant phenotype of HCC. Comprehensive analysis of the prognostic impact of MIR22HG in HCC revealed a beneficial effect of MIR22HG on the survival outcome of HCC patients. Seven cases of MIR22HG deep deletion occurred in 360 of the cancer genome atlas (TCGA) provisional HCC samples. A total of 22 MIR22HG-TF-mRNA triplets in HCC were predicted by the lncRNAmap. Co-expressed genes of MIR22HG, identified by weighted correlation network analysis (WGCNA), mainly participated in the pathways involving osteoclast differentiation, chemokine signaling pathways, and hematopoietic cell lineage. In vivo experiments demonstrated that nitidine chloride could stimulate MIR22HG expression in HCC xenografts. Conclusion: In summary, MIR22HG may play a tumor-suppressive role in HCC by coordinating with predicted TFs and co-expressed genes, such as NLRP3, CSF1R, SIGLEC10, and ZEB2, or by being controlled by nitidine chloride.

18.
Int J Pharm ; : 118846, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31821877

RESUMO

Otitis media, commonly known as middle ear inflammation, is among one of the most common maladies and results in significant morbidity such as loss of hearing. In view of the bacteria invasion such as Staphylococcus aureus causes the majority forms of otitis media, drug treatment generally uses antibacterial by topical or systematic approach. However, the effectiveness of antibacterial is diminishing because of the rapid emergence of antibiotic-resistant bacterial strains. Here, we designed and fabricated a silver nanoparticle (AgNPs)-based multicomponent hybrid nanocomposite termed as TSIIA @ CS/Lys @ AgNPs, which was comprised of a AgNPs core, a chitosan (CS) or lysozyme (Lys) middle layer, and a Tanshinone IIA (TSIIA) inclusion outlayer. Coating of CS or Lys to AgNPs through electrostatic interaction probably produced a core-shell nanocomplex resembling the endocarp of walnut. This design could reduce the dosage of AgNPs while maintaining antibacterial activity possibly due to the favorable interactions between nanocomplex and bacteria. The deposition of Chinese herb active component TSIIA by inclusion complexation formed the out layer of hybrid nanocomposite towards an improved antibacterial performance, which showed a therapeutic effect against acute otitis media of guinea pig comparable to the clinical commercial-used ofloxacin administrated by injection. The hybrid nanocomposite, when dispersed in poly (lactic-co-glycolic acid)/N-methyl-2-pyrrolidone (PLGA/NMP) solution as an in-situ organogel, not only maintained the therapeutic effectiveness, but also possessed the advantage of lower injection frequency compared with solution formulation. In addition, no obvious toxicity to the basilar membrane and epithelia tissue was observed after the healthy guinea pigs were treated with hybrid nanocomposite or organogel. This study provides a promising strategy to develop hybrid nanocomposite with enhanced antibacterial efficacy and also opens a new way for the establishment of efficient therapeutic systems with reduced administration frequency as substitute of antibiotics to treat otitis media.

19.
Oxid Med Cell Longev ; 2019: 6181754, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827684

RESUMO

Severe acute pancreatitis (SAP) is a challenging disease with high morbidity and mortality, often complicated by multiple organ dysfunction syndrome (MODS). The intestine, a major organ involved in MODS, correlates strongly with the evolution of the disease. In this study, we demonstrated that the DPP4 inhibitor, sitagliptin, protects SAP-associated intestinal injury both in vitro and in vivo. These beneficial effects were achieved by suppressing oxidative stress and inflammatory responses. Moreover, in sitagliptin-treated SAP mice, expression of Nrf2 was induced and that of NF-κB was reduced, compared to the control SAP mice. In addition, we used Nrf2-/- mice to test the protective effect of Nrf2 during sitagliptin treatment of SAP; our results indicated that Nrf2-/- mice had greater pancreatic and intestinal injury than wild-type mice. Taken together, high levels of ROS induced by SAP may be inhibited by sitagliptin, possibly by inactivating the Nrf2-NF-κB pathway.

20.
Molecules ; 24(23)2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31783525

RESUMO

A series of ferric chloride-lignin sulfonate (FCLS) was prepared from ferric chloride and lignin sulfonate to be used as shale inhibitor. The swelling rate of clay with FCLS-2 (w/w = 0.3%) decreased to 41.9%. Compared with control, FCLS-2 displayed high inhibitive ability against the hydrating and swelling processes of clay. Thus, the swelling degree of samples with FCLS-2 was much lower than that of the control, as well as the mud ball was more stable in FCLS-2 solution. Essentially, these excellent performances in inhibitor were assigned to the hydrogen bonding, electrostatic interaction and anchoring between FCLS-2 and other components. In addition, FCLS-2 has good compatibility with other common drilling fluid additives, and it can reduce the viscosity of systems, regardless of the room temperature or high temperature.

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