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1.
J Mol Model ; 26(4): 78, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32180045

RESUMO

A series of energetic polynitromethyl and polynitromethyl substituents were designed and then incorporated into 2,3-dihydro pyrazino [2,3-e] [1, 2, 3, 4] tetrazine molecule. The heat of formations, frontier molecular orbitals, electronic densities, electrostatic potentials, thermal stability, and impact sensitivity of the designed compounds were predicted by density functional theory. Most of the title compounds possess excellent comprehensive performance, that is, large densities (1.90 to 2.35 g cm-3), high detonation velocities (9.00 to 13.02 km s-1), and high detonation pressures (40.00 to 85.41 GPa). Due to their good detonation properties, suitable thermal stability, and other properties, 10 compounds (A2, A3, A6, B3, B6, C6, D3, D6, E3, and E6) were screened as the potential high-energy density compounds. The results and the ideas of molecular design proposed in this work are expected to assist the experimental researchers in the synthesis of new fluorine- and oxygen-rich high-energy density compounds.

2.
Dalton Trans ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32101178

RESUMO

The post-functionalization of six novel symmetric and asymmetric meso-expanded Co(iii) corroles through Suzuki-Miyaura coupling reactions has been successfully accomplished and is reported along with their structural characterization. An analysis of the structure-property relationships of the optical and redox properties of the corroles has been carried out by comparing their optical spectra and their electrochemical properties. The results demonstrate that post-functionalized meso-expanded Co(iii) triarylcorroles exhibit enhanced electrocatalyzed oxygen reduction reaction (ORR) activity and that their reactivity can be controlled by modulating the electronic structure, the functionalization and the number of coupled meso-substituents.

3.
J Mol Model ; 26(3): 41, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009197

RESUMO

Boron-contained compounds are one kind of new energetic materials, and have been synthesized successfully lately. However, the effects of introduced boron atoms into the energetic system are unclear. In this work, using the known insensitive energy crystal 2,6-diamino-3,5-dinitropyrazine-l-oxide (LLM-105) as the model compound, boron doping effects on its crystal structure, band gap and structure, intermolecular contacts, sensitivity, elastic property, optical absorption behavior, and dielectric function were studied by the first principles calculations and Hirshfeld surface analysis. One B atom was doped at four different doping sites in the ring (two kinds of nitrogen N1/N2 and carbon atoms C3/C4), respectively, and formed four new crystals LLM-105-B1/B2/B3/B4. The results showed that the B atom and its doping site both make great influence on the structure and properties. The B doping obviously decreased the band gap and weakened the strength of intermolecular contacts, giving rise to higher sensitivity and worse safety. Especially for LLM-105-B4 which has a 0 eV value of band gap, the doped B atom made great contributions to the density of states around the Fermi level, leading to the suddenly move down of lowest unoccupied molecular orbital and directly link of total density of states at the Fermi level. Doping the B atom at the site C3 improved the ductility and plasticity of LLM-105, while LLM-105-B2 was found to be the most brittle and anisotropic crystal. Doping B atoms at sites N2 and C4 increased the absorption to green, orange, and red lights, while the absorption strength to the infrared light was enhanced in most cases. The dielectric constant and polarity were significantly increased by doping boron atoms at sites C3 and C4.

4.
Asian-Australas J Anim Sci ; 33(4): 547-555, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31480202

RESUMO

OBJECTIVE: Apoptosis of ovarian granulosa cells (GCs) affects mammalian follicular development and fecundity. This study aimed to explore the regulatory relationship between microRNA-26a (miR-26a) and the 3ß-hydroxysteroid-Δ24-reductase gene (DHCR24) gene in porcine follicular granular cells (pGCs), and to provide empirical data for the development of methods to improve the reproductive capacity of pigs. METHODS: The pGCs were transfected with miR-26a mimic, miR-26a inhibitor and DHCR24-siRNA in vitro. The cell apoptosis rate of pGCs was detected by the flow cytometry. The secretion levels of estradiol (E2) and progesterone (P) in pGCs were detected by enzymelinked immunosorbent assay. Double luciferase validation system was used to detect the binding sites between miR-26a and DHCR24 3'-UTR region. Qualitative real-time polymerase chain reaction and Western blotting were used to verify the DHCR24 mRNA and protein expression in pGCs, respectively, after transfecting with miR-26a mimic and miR-26a inhibitor. RESULTS: Results showed that enhancement of miR-26a promoted apoptosis, and inhibited E2 and P secretion in pGCs. Meanwhile, inhibition of DHCR24 also upregulated the Caspase-3 expression, reduced the BCL-2 expression, promoted pGCs apoptosis, and inhibited E2 and P secretion in pGCs. There were the binding sites of miR-26a located within DHCR24 3'-UTR. Up-regulation of miR-26a inhibited DHCR24 mRNA and protein expression in pGCs. CONCLUSION: This study demonstrates that miR-26a can promote cell apoptosis and inhibit E2 and P secretion by inhibiting the expression of DHCR24 in pGCs.

5.
Reprod Domest Anim ; 55(2): 217-228, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31869480

RESUMO

Litter size is one of the most important economic traits in pig production. Recent studies identified that deoxynivalenol (DON), a widespread toxin in fodder, was associated with animal prolificacy. However, the underlying mechanisms have not yet been completely elucidated. Here, we used porcine ovary granulosa cells (pGCs) as a vector to establish DON concentration-time models and performed cell morphology and transcriptome analysis to identify and analyse the effects of DON on reproductive performance in swine. The results showed that DON can induce morphological changes and apoptosis of pGCs, while inhibiting cell proliferation. Moreover, these effects of DON on pGCs were dose-dependent. After treatment of pGCs with different concentrations of DON, the percentage of cells in S phase and G2/M phase increased. RNA-seq analyses revealed 5,937 differentially expressed genes, of which 1995 were down-regulated and 3,942 were up-regulated after DON treatment. KEGG enrichment analysis indicated important metabolic pathways such as IL-17 signalling pathway, eukaryotic ribosome synthesis pathway, RNA transport pathway and RNA degradation. Based on our results, we speculate that the effects of DON are related to the DNA damage process. Our study provides novel insights and a foundation to further understand the effect of DON on swine prolificacy.

6.
Cell ; 179(4): 829-845.e20, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31675496

RESUMO

The immune microenvironment of hepatocellular carcinoma (HCC) is poorly characterized. Combining two single-cell RNA sequencing technologies, we produced transcriptomes of CD45+ immune cells for HCC patients from five immune-relevant sites: tumor, adjacent liver, hepatic lymph node (LN), blood, and ascites. A cluster of LAMP3+ dendritic cells (DCs) appeared to be the mature form of conventional DCs and possessed the potential to migrate from tumors to LNs. LAMP3+ DCs also expressed diverse immune-relevant ligands and exhibited potential to regulate multiple subtypes of lymphocytes. Of the macrophages in tumors that exhibited distinct transcriptional states, tumor-associated macrophages (TAMs) were associated with poor prognosis, and we established the inflammatory role of SLC40A1 and GPNMB in these cells. Further, myeloid and lymphoid cells in ascites were predominantly linked to tumor and blood origins, respectively. The dynamic properties of diverse CD45+ cell types revealed by this study add new dimensions to the immune landscape of HCC.

7.
J Mol Model ; 25(11): 340, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713742

RESUMO

In this study, 16 new energetic metal complexes [M(DNABT)(ATDO), M=Cu, Ni] were designed using the mixed complex construct strategy, which was based on two complementary oxygen-rich high-energy ligands of 1,1'-dinitramino-5,5'-bistetrazole (DNABT) and 4-amino-4H-1,2,4-triazole-3,5-diol (ATDO), then combined with metals Cu and Ni, and further adjusted by the introduction of NO2 and NH2. The molecular and electronic structures, heat of formation (HOF), density, detonation velocity, detonation pressure, and sensitivity were investigated by the density functional theory method. The results showed that in metals, the position and amount of NO2/NH2 have great effects on the structure and property of metal complexes, and these effects coupled with each other. N-NO2 bond is the relatively weak bond, and its max length is related with the sensitivity closely. The designed metal complexes all have high HOF (673~868 kJ mol-1), high density (2.06~2.14 g cm-3), and ideal oxygen balance (- 19.2~- 6.7%), which further make them have higher detonation velocity (8.76~9.84 km s-1) and detonation pressure (37.4~46.6 GPa) than three famous high-energy compounds 1,3,5-trinitro-1,3,5-triazine (RDX); 1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX); or even 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20). At the same time, they are less sensitive than RDX, HMX, and CL-20, making them potential candidates for high-energy density compounds.

8.
Dalton Trans ; 48(38): 14467-14477, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31528897

RESUMO

Herein, three polypyrrole-based nanohybrids were designed and prepared via a nucleophilic substitution reaction, i.e., peripherally substituted porphyrin-functionalized PPy (TPP-PPy), axially coordinated metal-porphyrin-functionalized PPy (SnTPP-PPy), and polypyrrole ternary nanohybrids co-functionalized with peripherally substituted porphyrins and axially coordinated metal-porphyrins (TPP-PPy-SnTPP). The TPP-PPy, SnTPP-PPy and TPP-PPy-SnTPP nanohybrids exhibited improved nonlinear optical and optical limiting performances when compared to the individual PPy and porphyrins under 4 ns, 532 nm laser pulses. Their improved optical nonlinearities were ascribed to a combination of mechanisms and efficient charge transfer effect between the porphyrins and PPy. The charge transfer effect between the porphyrins and PPy was confirmed by UV-vis absorption, fluorescence and electrochemical impedance spectroscopy. The TPP-PPy-SnTPP ternary nanohybrid exhibited the best nonlinear absorption, nonlinear refraction and optical limiting performances because of more effective charge transfer effect, which provides a new avenue for the development of polypyrrole-porphyrin systems in the fields of nonlinear optics and optoelectronic devices.

9.
Cell Death Discov ; 5: 131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482012

RESUMO

We previously reported that p53-mediated apoptosis is determined by severity of DNA damage, not by the level of p53, in doxorubicin-treated prostate cancer cells. In addition to doxorubicin, our results here indicated that camptothecin and bortezomib, which are a topoisomerase 1 poison and a 26 S proteasome inhibitor, respectively, could also induce apoptosis in a p53-dependent manner in prostate cancer. Then, we examined whether p53-mediated apoptosis induced by genotoxic and non-genotoxic stress occur in the same or a different way. By using dominant negative p53 to compete with wild-type p53 in transcription activity, we demonstrated that p53-mediated apoptosis in response to doxorubicin- or camptothecin-induced genotoxic stress is transcription-independent. In contrast, p53-mediated apoptosis from bortezomib-induced stress is transcription-dependent. Interestingly, we also found that doxorubicin-induced p21 expression is activated by p53 in transcription-dependent manner, while camptothecin-induced p21 expression is p53-independent. We then investigated the p53 ratio of nucleus to cytosol corresponding to low and high dose doxorubicin, camptothecin, or bortezomib treatment. The results suggested that p53 translocation from cytoplasm to nucleus actively drives cells toward apoptosis in either transcription-dependent or -independent manner for responding to non-genotoxic or genotoxic stress, respectively.

10.
Trials ; 20(1): 528, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443731

RESUMO

BACKGROUND: The prognostic benefits and safety of extended lymphadenectomy for hilar cholangiocarcinoma remain uncertain. The available evidence is still insufficient concerning its retrospective aspect. The aim of this study is to explore the clinical effect and safety of extended lymphadenectomy compared to regional lymphadenectomy in patients with hilar cholangiocarcinoma. METHODS: The Relay-HC trial is a prospective, multicenter, and randomized controlled trial. Seven hundred and thirty-four eligible patients with resectable perihilar cholangiocarcinoma across 15 tertiary hospitals in China will be randomly assigned (1:1) to receive either regional lymphadenectomy or extended lymphadenectomy. The primary objective is to determine the overall survival after the two approaches. Secondary objectives of the study include the evaluation of perioperative mortality, postoperative complication, and disease-free survival. This study has been approved by the ethics committee of each participating hospital. DISCUSSION: The Relay-HC trial is designed to investigate the prognostic benefits and safety of expanded lymphadenectomy for hilar cholangiocarcinoma. Currently, it has never been investigated in a prospective randomized controlled clinical trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR1800015688 . Registered on 15 April 2018.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Tumor de Klatskin/cirurgia , Excisão de Linfonodo/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , China , Intervalo Livre de Doença , Feminino , Humanos , Tumor de Klatskin/mortalidade , Tumor de Klatskin/secundário , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Adulto Jovem
11.
J Colloid Interface Sci ; 556: 159-171, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31445445

RESUMO

In this contribution, two constituent-tunable metallophthalocyanine covalent organic polymers (MPc-COPs) covalently attached to graphene oxide (GO-PcP 1 and GO-PcP 2) were rationally designed and fabricated for optoelectronics and electrocatalysis. The resultant GO-PcP nanohybrids exhibit markedly enhanced nonlinear optical and optical limiting performances over those of their components and physical mixtures at 532 nm in the nanosecond pulse range. The optical nonlinearity can be further optimized by tuning the linkage type between the four-branched tetraamine metallophthalocyanine units. The hydrogen evolution reaction (HER) is investigated by linear sweep voltammetry in a 0.5-M H2SO4 aqueous solution. Under optimal conditions, the overpotentials needed to reach 1 mA cm-2 are measured as 237 and 210 mV for GO-PcP 1 and GO-PcP 2, respectively, which places GO-PcP 2 as the best metallophthalocyanine polymer-based HER catalyst to be reported in the literature. The improved performances were ascribed to the positive synergistic effects between MPc-COPs and GO. Notably, the present study introduces a new strategy for the precise preparation of MPc-COP-based nanomaterials while exploring their applications to develop highly efficient optical limiters and electrocatalysts.

12.
J Mol Model ; 25(9): 283, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31468179

RESUMO

By using the density functional theory method, we investigated the heats of formation (HOFs), electronic structure, detonation properties, thermal stability and sensitivity for a set of pyrazino [2, 3-e] [1, 2, 3, 4] tetrazine derivatives with different substituents and different numbers of N-oxides. Our findings reveal that the HOFs of the derivatives decrease dramatically with the increasing number of N-oxides. The effects of the substituents on the HOMO-LUMO gaps are coupled with those of the N-oxides. The calculated detonation properties point out that -NF2, -ONO2 and an increasing number of N-oxides are very helpful for improving the detonation performance of the designed derivatives. The bond dissociation energies of the weakest bonds indicate that a majority of our designed compounds have better thermal stability. The -NH2 group is very useful to decrease the free space value. Most of the derivatives have higher h50 values compared with parent molecules. Considering the sensitivity, thermal stability and detonation performance, four compounds could be considered as potential candidates of high-energy density compounds.

13.
Biomed Res Int ; 2019: 9258075, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31309120

RESUMO

Cancer metastasis has been demonstrated as it is the culmination of a cascade of priming steps. Increasing evidence has shown that tumor-derived molecular components (TDMCs) are known as extra cellular vesicle and nonvesicle factors and serve as versatile intercellular communication vehicles which can mediate signaling in the tumor microenvironment while creating the premetastatic niche. Noncoding RNAs (ncRNAs) as one of the TDMCs have been proved in participating in the formation of the premetastatic niche. Understanding the premetastatic niche formation mechanisms through TDMCs, especially ncRNAs may open a new avenue for cancer metastasis therapeutic strategies. In this review, recent findings regarding ncRNAs function were summarized, and then the interaction with the premetastatic niche formation was studied, which highlight the potential of using ncRNAs for cancer diagnosis and therapeutic effect.


Assuntos
Comunicação Celular , Vesículas Extracelulares/metabolismo , Neoplasias/metabolismo , RNA Neoplásico/metabolismo , RNA não Traduzido/metabolismo , Transdução de Sinais , Microambiente Tumoral , Animais , Vesículas Extracelulares/patologia , Humanos , Metástase Neoplásica , Neoplasias/patologia
14.
Phys Chem Chem Phys ; 21(30): 16830-16837, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31334707

RESUMO

High frequency magnetic precessions with strong intensity are strongly desired in material systems for high performance magnetic memory or nano-oscillator applications with ultrafast manipulation speed. Here, we demonstrate an exchange-coupled asymmetric composite film structure of Ta/Pd/[Pd/Co]5/Cu(tCu)/[Co/Ni]5/Ta with adjustable strong perpendicular magnetic anisotropy and interlayer coupling strength, in which the dynamic magnetic properties are systematically studied by using time-resolved magneto-optical Kerr effect spectroscopy. It is demonstrated that the in-phase precession frequency is between those of the single hard magnetic [Pd/Co]5 and soft [Co/Ni]5 multilayers, which can be significantly enhanced for the strongly coupled case at tCu < 1 nm. Moreover, in the weakly coupled samples with tCu = 1.0-3.0 nm, besides the common in-phase acoustic mode, an out-of-phase optical mode occurs simultaneously with a frequency even higher than that of the hard magnetic [Pd/Co]5 layer. The optical mode precession frequency and amplitude show an unusual non-monotonic variation trend with the increase of tCu, which has been theoretically analyzed and attributed to the co-effect of decreased coupling strength and increased magnetic anisotropy field difference between the two multilayer stacks. Moreover, by adjusting tCu and the [Co/Ni] repetition number N, an optical mode of strong intensity can be actively achieved, even reaching 80% as compared to the acoustic mode. These results provide effective control and better understanding of magnetic dynamics in perpendicular composite films, which are of key importance for developing ultrafast spintronics-based devices.

15.
J Mol Graph Model ; 90: 144-152, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31082640

RESUMO

A systematical theoretical study of structure, vibrational properties, and initial decomposition mechanisms of δ-HMX in the pressure range of 0-30 GPa was performed by using density functional theory (DFT). The results show that HMX presents a structural transition at 8 GPa, which has not been found in experiments yet. As the pressure increases, the intra-molecular hydrogen bonding interactions enhance gradually, but they have a sudden decrease at 8 GPa. A comprehensive analysis of density of states and population analysis indicates that the N-N bonds are prone to cleave upon impact or stimulation and the N-NO2 group may act as the active site of the initial decomposition of δ-HMX under the compression. The pressure-dependent frequency shifts indicate that all the modes move towards higher vibrational frequencies. Between the two competition decomposition mechanisms of the δ-HMX crystal, the N-NO2 homolysis becomes more preferential than the HONO elimination as the pressure increases. Our studies may shed a light on a new understanding of the initial decomposition mechanisms of energetic materials under high pressures.

16.
Anim Sci J ; 90(6): 719-727, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30983045

RESUMO

Apoptosis of granulosa cells affects follicular atresia and reproduction and is regulated by miRNAs and the expression of certain genes. For the present study, we investigated the regulatory relationship between microRNA-222 (miR-222) and THBS1 in porcine follicular granulosa cells (pGCs) and its effects on apoptosis to provide empirical data for developing methods to improve pig fecundity. Results revealed that miR-222 promotes the proliferation of pGCs. MiRNA mimics and luciferase reporter assays revealed that miR-222 functions as an anti-apoptotic factor in pGCs. MiR-222 mimics in pGCs result in the upregulation of the anti-apoptotic BCL-2 gene, down-regulation of the proapoptotic caspase-3 gene, and inhibition of apoptosis. MiR-222 inhibitors reduced BCL-2 and had no significant effect on caspase-3. MiR-222 mimics promoted estrogen levels. Inhibition of THBS1 inhibited pGC apoptosis. Transfection of THBS1-siRNA reduced the proapoptotic BAX gene. MiR-222 can directly target the 3'-untranslated region of the THBS1 gene. MiR-222 mimics suppressed THBS1 mRNA and proteins, but these were upregulated by the miR-222 inhibitor. Transfection of THBS1-siRNA resulted in the inhibition of the miR-222 inhibitor, which suggests that miR-222 inhibits pGC apoptosis by targeting THBS1. These findings suggest that miR-222 and THBS1 play important roles in follicular atresia, ovarian development, and female reproduction.


Assuntos
Apoptose/genética , Células da Granulosa/patologia , MicroRNAs/fisiologia , Folículo Ovariano/citologia , Trombospondinas/fisiologia , Animais , Caspase 3 , Proliferação de Células/genética , Células Cultivadas , Feminino , Fertilidade/genética , Genes bcl-2 , MicroRNAs/genética , Reprodução/genética , Suínos , Trombospondinas/genética
17.
Angew Chem Int Ed Engl ; 58(18): 5925-5929, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30843636

RESUMO

A hybrid thia-norhexaphyrin comprising a directly linked N-confused pyrrole and thiophene unit (1) revealed unique macrocycle transformations to afford multiply inner-annulated aromatic macrocycles. Oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone triggered a cleavage of the C-S bond of the thiophene unit, accompanied with skeletal rearrangement to afford unique π-conjugated products: a thiopyrrolo-pentaphyrin embedded with a pyrrolo[1,2]isothiazole (2), a sulfur-free pentaphyrin incorporating an indolizine moiety (3), and a thiopyranyltriphyrinoid containing a 2H-thiopyran unit (4). Furthermore, 2 underwent desulfurization reactions to afford a fused pentaphyrin containing a pyrrolizine moiety (5) under mild conditions. Using expanded porphyrin scaffolds, oxidative thiophene cleavage and desulfurization of the hitherto unknown N-confused core-modified macrocycles would be a practical approach for developing unique polypyrrolic aromatic macrocycles.

18.
J Am Chem Soc ; 141(13): 5294-5302, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30849868

RESUMO

Expanded porphyrins have been attracting increasing attention owing to their unique optical and electrochemical properties as well as switchable aromaticity. Toward material applications, regioselective functionalization of the expanded porphyrins at their periphery is indeed challenging due to the presence of multiple reactive sites. Herein, a set of regioselective halogenated isomers (L5-Br-A/B/C) of neo-confused isosmaragdyrin (L5) are synthesized by a combination of the halogenation reaction of L5 and sequential macrocycle-to-macrocycle transformation reactions of its halogenated isomers. On this basis, the regioselectively functionalized isosmaragdyrins are utilized as building blocks for constructing multichromophoric porphyrinoids, specifically, heterodyads L5-ZnP-A/B/C, in which a common zinc porphyrin is linked at three different pyrrolic positions of isosmaragdyrins, respectively, by Sonogashira coupling reactions. The highly efficient energy cascade from porphyrin to isosmaragdyrin is elucidated using steady-state/time-resolved spectroscopies and theoretical calculations. Notably, the energy transfer processes from the porphyrin to the isosmaragdyrin moieties as well as the excitation energy transfer rates in L5-ZnP-A/B/C are highly dependent on the linking sites by through-bond and Förster-type resonance energy transfer mechanisms. The site-selective functionalization and subsequent construction of a set of heterodyads of the expanded porphyrinoid would provide opportunities for developing new materials for optoelectronic applications.

19.
Acta Biochim Biophys Sin (Shanghai) ; 51(2): 159-167, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30668625

RESUMO

In the present study, we aimed to investigate the role of endoplasmic reticulum stress (ERS) and its related inflammation and angiogenesis in liver fibrosis in a rat model of combined hypoxia and nonalcoholic steatohepatitis (NASH) and to confirm whether the intervention of hypoxia-inducible factor 1α (HIF1α) can improve fibrosis. Liver histological changes and biochemical indices, HIF1α, inflammatory factors, ERS-related parameters (GRP78, CHOP, caspase-3, and caspase-12), and angiogenesis indices (VEGFA, VEGFR2, and CD34) were evaluated. Compared with the control rats, the liver tissue of rats with hypoxia and NASH had obvious NASH characteristics and hepatic fibrosis was significantly aggravated, including bridging fibrosis in some rats. The mRNA expression levels of HIF1α, VEGFA, and VEGFR2 and total immunohistochemical staining scores of VEGFR2 and CD34 were significantly increased. In addition, HIF1α silencing significantly decreased HIF1α, biochemical indices (ALT, AST, and TG), inflammatory factors (TNFα, IL6, and IL1ß), and angiogenesis indices (CD34 and VEGFR2), consequently, improved the hepatic fibrosis score in the rat model of combined hypoxia and NASH. Taken together, chronic intermittent hypoxia accelerates liver fibrosis in rats with combined hypoxia and NASH via angiogenesis rather than ERS and HIF1α intervention can improve liver fibrosis, angiogenesis, inflammatory factors, and biochemical indices. Therefore, HIF1α is a key regulatory factor of liver fibrosis in rats with combined hypoxia and NASH.


Assuntos
Estresse do Retículo Endoplasmático/genética , Hipóxia , Cirrose Hepática/genética , Neovascularização Patológica/genética , Hepatopatia Gordurosa não Alcoólica/genética , Animais , Doença Crônica , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Masculino , Neovascularização Patológica/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Interferência de RNA , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
20.
J Clin Pathol ; 72(4): 295-303, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30610005

RESUMO

AIMS: To evaluate stromal histopathological features and immunostaining expression for differential diagnosis of low- and high-grade dysplastic nodules (HGDN) to early and progressed hepatocellular carcinomas (eHCC, pHCC). MATERIALS: We evaluated sinusoid capillarisation (SC), solitary artery (SA), ductular reaction (DR), stromal invasion and expression of six biomarkers (GPC3, HSP70, GS, CD34, CK19, EpCAM) in a series of 97 cases. RESULTS: Stromal morphological changes, including SC, DR and SA, exhibited significant differences in differential diagnosis. In one indicator, SC had the best sensitivity (90.00%) and accuracy (85.42%), and SA had the best specificity at 88.89 %. In combinations, SC +and SA +were favourable and optimal. The immunoreactivity of GPC3, HSP70 and GS increased significantly in line with the stepwise progression of hepatocarcinogenesis. CONCLUSIONS: Stromal histopathology features are useful for diagnosing HGDN, eHCC and small HCC. The immunostaining panel of GPC3, HSP70 and GS can also be supplementary.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/química , Neoplasias Hepáticas/patologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Células Estromais/química , Células Estromais/patologia , Adulto , Idoso , Carcinoma Hepatocelular/cirurgia , Feminino , Glutamato-Amônia Ligase/análise , Glipicanas/análise , Proteínas de Choque Térmico HSP70/análise , Humanos , Imuno-Histoquímica , Imunofenotipagem/métodos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fenótipo , Lesões Pré-Cancerosas/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos
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