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1.
Cell ; 187(5): 1127-1144.e21, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38428393

RESUMEN

Chloroplasts are green plastids in the cytoplasm of eukaryotic algae and plants responsible for photosynthesis. The plastid-encoded RNA polymerase (PEP) plays an essential role during chloroplast biogenesis from proplastids and functions as the predominant RNA polymerase in mature chloroplasts. The PEP-centered transcription apparatus comprises a bacterial-origin PEP core and more than a dozen eukaryotic-origin PEP-associated proteins (PAPs) encoded in the nucleus. Here, we determined the cryo-EM structures of Nicotiana tabacum (tobacco) PEP-PAP apoenzyme and PEP-PAP transcription elongation complexes at near-atomic resolutions. Our data show the PEP core adopts a typical fold as bacterial RNAP. Fifteen PAPs bind at the periphery of the PEP core, facilitate assembling the PEP-PAP supercomplex, protect the complex from oxidation damage, and likely couple gene transcription with RNA processing. Our results report the high-resolution architecture of the chloroplast transcription apparatus and provide the structural basis for the mechanistic and functional study of transcription regulation in chloroplasts.


Asunto(s)
ARN Polimerasas Dirigidas por ADN , Plastidios , Cloroplastos/metabolismo , Microscopía por Crioelectrón , ARN Polimerasas Dirigidas por ADN/genética , Nicotiana/genética , Fotosíntesis , Plastidios/enzimología
2.
Inorg Chem ; 63(15): 6767-6775, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38569160

RESUMEN

Electrolytic hydrogen production via water splitting holds significant promise for the future of the energy revolution. The design of efficient and abundant catalysts, coupled with a comprehensive understanding of the hydrogen evolution reaction (HER) mechanism, is of paramount importance. In this study, we propose a strategy to craft an atomically precise cluster catalyst with superior HER performance by cocoupling a Mo2O4 structural unit and a Cu(I) alkynyl cluster into a structured framework. The resulting bimetallic cluster, Mo2Cu17, encapsulates a distinctive structure [Mo2O4Cu17(TC4A)4(PhC≡C)6], comprising a binuclear Mo2O4 subunit and a {Cu17(TC4A)2(PhC≡C)6} cluster, both shielded by thiacalix[4]arene (TC4A) and phenylacetylene (PhC≡CH). Expanding our exploration, we synthesized two homoleptic CuI alkynyl clusters coprotected by the TC4A and PhC≡C- ligands: Cu13 and Cu22. Remarkably, Mo2Cu17 demonstrates superior HER efficiency compared to its counterparts, achieving a current density of 10 mA cm-2 in alkaline solution with an overpotential as low as 120 mV, significantly outperforming Cu13 (178 mV) and Cu22 (214 mV) nanoclusters. DFT calculations illuminate the catalytic mechanism and indicate that the intrinsically higher activity of Mo2Cu17 may be attributed to the synergistic Mo2O4-Cu(I) coupling.

3.
Immunopharmacol Immunotoxicol ; : 1-12, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39134472

RESUMEN

BACKGROUND: Gremlin1 is a multifunctional protein whose expression is demonstrated to be involved in a series of physiology and pathological processes. The association between Gremlin1 and apcial periodontitis (AP) has been established. M1-polarized macrophages are crucial immune cells that exacerbate the progression of apical periodontal inflammatory response, but the function of Gremlin1 during macrophages activation in periapical lesions is still unclear. This study attempts to explore the regulatory effects of Gremlin1 on macrophage polarization on apical periodontitis microenviroment. METHODS: Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western blot, immunofluorescence staining were performed. RESULTS: Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The in vitro experiments confirmed the above results. CONCLUSION: Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP.

4.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2754-2765, 2024 May.
Artículo en Zh | MEDLINE | ID: mdl-38812176

RESUMEN

This study deciphered the ameliorating effect and molecular mechanism of the total glucosides of White Paeony Capsules(TGP) in the treatment of mice model with acute lung injury(ALI) via NOD-like receptor thermal protein domain associated protein 3(NLRP3) signaling pathway of the inflammasome. The study established an inflammasome activation model of primed bone marrow-derived macrophages(BMDMs), and its molecular mechanism was investigated by Western blot(WB), immunofluorescence staining, enzyme-linked immunosorbent assay(ELISA), and flow cytometry. C57BL/6J mice were randomly divided into a blank control group, a TGP group, a model group(LPS group), LPS+low-and high-dose TGP groups, LPS+MCC950 group, and LPS+MCC950+TGP group, with eight mice per group. The ALI model was induced in mice. Finally, bronchoalveolar lavage fluid(BALF) and lung tissue were collected. Lung index and lung weight wet-to-dry ratio were determined for each group of mice. The pathological changes in lung tissue were observed through hematoxylin-eosin(HE) staining. The number of neutrophils in the BALF of each group was detected using flow cytometry. The levels of interleukin(IL)-1ß, IL-6, and tumor necrosis factor(TNF)-α in the BALF were determined by ELISA. The expressions of IL-1ß, IL-18, IL-6, and TNF-α in the lung tissue were determined by real-time quantitative PCR(RT-qPCR). This study demonstrated that TGP dramatically blocked the activation of the NLRP3 inflammasome by inhibiting the production of upstream mitochondrial reactive oxygen species(mtROS) and the subsequent oligomerization of apoptosis-associated specks(ASC). Additionally, in the ALI mice model, compared with the blank control group, the model group showed alveolar structure rupture, thic-kening of alveolar septa, and dramatically increased lung index, lung weight wet-to-dry ratio in lung tissue, neutrophil count, and inflammatory factor levels. Compared with the model group, the pathological morphology of lung tissue was significantly ameliorated in the TGP and MCC950 groups, and the lung index and lung weight wet-to-dry ratio were significantly reduced. Neutrophil counts were reduced, and levels of inflammatory factors were significantly downregulated. Notably, compared with the MCC950 group, there was no significant difference in effect in the MCC950+TGP group. Collectively, the study reveals that TGP may ameliorate ALI in mice by inhibiting the activation of NLRP3 inflammasome, providing a safe and effective drug candidate for the prevention or treatment of ALI/ARDS.


Asunto(s)
Lesión Pulmonar Aguda , Medicamentos Herbarios Chinos , Glucósidos , Inflamasomas , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Paeonia , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Glucósidos/farmacología , Glucósidos/química , Ratones , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Masculino , Paeonia/química , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Cápsulas , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo
5.
Int J Mol Sci ; 24(3)2023 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-36768624

RESUMEN

Flame-retardant cycloaliphatic epoxy systems have long been studied; however, the research suffers from slow and unsatisfactory advances. In this work, we synthesized a kind of phosphorus-containing difunctional cycloaliphatic epoxide (called BCEP). Then, triglycidyl isocyanurate (TGIC) was mixed with BCEP to achieve epoxy systems that are rich in phosphorus and nitrogen elements, which were cured with 4-methylhexahydrobenzene anhydride (MeHHPA) to obtain a series of flame-retardant epoxy resins. Curing behaviors, flame retardancy, thermal behaviors, dielectric performance, and the chemical degradation behaviors of the cured epoxy system were investigated. BCEP-TGIC systems showed a high curing activity, and they can be efficiently cured, in which the incorporation of TGIC decreased the curing activity of the resin. As the ratio of BCEP and TGIC was 1:3, the cured resin (BCEP1-TGIC3) showed a relatively good flame retardancy with a limiting oxygen index value of 25.2%. In the cone calorimeter test, they presented a longer time to ignition and a lower heat release than the commercially available cycloaliphatic epoxy resins (ERL-4221). BCEP-TGIC systems presented good thermal stability, as the addition of TGIC delayed the thermal weight loss of the resin. BCEP1-TGIC3 had high dielectric performance and outperformed ERL-4221 over a frequency range of 1 HZ to 1 MHz. BCEP1-TGIC3 could achieve degradation under mild conditions in an alkali methanol/water solution. Benefiting from the advances, BCEP-TGIC systems have potential applications as electronic packaging materials in electrical and electronic fields.


Asunto(s)
Resinas Epoxi , Retardadores de Llama , Álcalis , Anhídridos , Electrónica , Fósforo , Resinas de Plantas
6.
Molecules ; 28(2)2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36677592

RESUMEN

Apigenin is a natural flavonoid with significant biological activity, but poor solubility in water and low bioavailability limits its use in the food and pharmaceutical industries. In this paper, apigenin-7-O-ß-(6″-O)-d-glucoside (AG) and apigenin-7-O-ß-(6″-O-succinyl)-d-glucoside (SAG), rare apigenin glycosyl and succinyl derivatives formed by the organic solvent-tolerant bacteria Bacillus licheniformis WNJ02 were used in a 10.0% DMSO (v/v) system. The water solubility of SAG was 174 times that of apigenin, which solved the application problem. In the biotransformation reaction, the conversion rate of apigenin (1.0 g/L) was 100% at 24 h, and the yield of SAG was 94.2%. Molecular docking showed that the hypoglycemic activity of apigenin, apigenin-7-glucosides (AG), and SAG was mediated by binding with amino acids of α-glucosidase. The molecular docking results were verified by an in vitro anti-α-glucosidase assay and glucose consumption assay of active compounds. SAG had significant anti-α-glucosidase activity, with an IC50 of 0.485 mM and enhanced glucose consumption in HepG2 cells, which make it an excellent α-glucosidase inhibitor.


Asunto(s)
Apigenina , Hipoglucemiantes , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Glicosilación , Apigenina/química , Simulación del Acoplamiento Molecular , alfa-Glucosidasas/metabolismo , Glucosa , Glucósidos/química
7.
Yi Chuan ; 45(5): 425-434, 2023 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-37194589

RESUMEN

Hypothalamic median eminence (ME) is a potential niche for neurons and oligodendrocytes, and trophic factors may regulate hypothalamic function by inducing cellular changes in the ME region. To determine whether diet-induced plasticity exists in hypothalamic stem cells dormant under physiological conditions, we used a combination of a normal diet, a high-fat diet, and a ketogenic diet (a low-carb, high-fat diet) to compare the proliferation of tanycytes (TCs) and oligodendrocyte precursor cells (OPCs) in the ME area of mice under the different diets. The results showed that the ketogenic diet could induce and promote the proliferation of OPCs in the ME area, and blocking the fatty acid oxidation program could inhibit the proliferation of OPCs induced by a ketogenic diet. This study preliminarily revealed the diet-induced effect on OPCs in the ME region and provided enlightenment for further study on the function of OPCs in the ME region.


Asunto(s)
Dieta Cetogénica , Células Precursoras de Oligodendrocitos , Ratones , Animales , Eminencia Media , Proliferación Celular , Ácidos Grasos , Diferenciación Celular
8.
Phys Chem Chem Phys ; 24(33): 19965-19974, 2022 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-35971867

RESUMEN

The combination of piezoelectricity with a nontrivial topological insulating phase in two-dimensional (2D) systems, namely piezoelectric quantum spin Hall insulators (PQSHI), is intriguing for exploring novel topological states toward the development of high-speed and dissipationless electronic devices. In this work, we predict a PQSHI Janus monolayer VCClBr constructed from VCCl2, which is dynamically, mechanically and thermally stable. In the absence of spin orbital coupling (SOC), VCClBr is a narrow gap semiconductor with a gap value of 57 meV, which is different from Dirac semimetal VCCl2. The gap of VCClBr is due to a built-in electric field caused by asymmetrical upper and lower atomic layers, which is further confirmed by the external-electric-field induced gap in VCCl2. When including SOC, the gap of VCClBr is increased to 76 meV, which is larger than the thermal energy of room temperature (25 meV). The VCClBr is a 2D topological insulator (TI), which is confirmed by Z2 topological invariant and nontrivial one-dimensional edge states. It is proved that the nontrivial topological properties of VCClBr are robust against strain (biaxial and uniaxial cases) and external electric fields. Due to broken horizontal mirror symmetry, only an out-of-plane piezoelectric response can be observed, when a biaxial or uniaxial in-plane strain is applied. The predicted piezoelectric strain coefficients d31 and d32 are -0.425 pm V-1 and -0.219 pm V-1, respectively, and they are higher than or compared with those of many 2D materials. Finally, Janus monolayer VCFBr and VCFCl (dynamically unstable) are also constructed, and they are still PQSHIs. Moreover, the d31 and d32 of VCFBr and VCFCl are higher than those of VCClBr, and the d31 (absolute value) of VCFBr is larger than one. According to out-of-plane piezoelectric coefficients of VCXY (X ≠ Y = F, Cl and Br), CrX1.5Y1.5 (X = F, Cl and Br; Y = I) and NiXY (X ≠ Y = Cl, Br and I), it is concluded that the size of the out-of-plane piezoelectric coefficient has a positive relation with the electronegativity difference of X and Y atoms. Our studies enrich the diversity of Janus 2D materials, and open a new avenue in the search for PQSHI with a large out-of-plane piezoelectric response, which provides a potential platform in nanoelectronics.

9.
Chem Biodivers ; 19(2): e202100809, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34931450

RESUMEN

This work deals with the design and synthesis of 18 barbituric acid derivatives bearing 1,3-dimethylbarbituric acid and cinnamic acid scaffolds to find potent anticancer agents. The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay. Flowcytometry was performed to determine the cell cycle arrest, apoptosis, ROS levels and the loss of MMP. The ratios of GSH/GSSG and the MDA levels were determined by using UV spectrophotometry. The results revealed that introducing substitutions (CF3 , OCF3 , F) on the meta- of the benzyl ring of barbituric acid derivatives led to a considerable increase in the antiproliferative activities compared with that of corresponding ortho- and para-substituted barbituric acid derivatives. Mechanism investigation implied that the 1c could increase the ROS and MDA level, decrease the ratio of GSH/GSSG and MMP, and lead to cell cycle arrest. Further research is needed for structural optimization to enhance hydrophilicity, thereby improve the biological activity of these compounds.


Asunto(s)
Antineoplásicos , Diseño de Fármacos , Antineoplásicos/química , Apoptosis , Barbitúricos , Línea Celular Tumoral , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad
10.
Genomics ; 113(1 Pt 1): 57-65, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33227410

RESUMEN

The aim of this study was to elucidate the roles played by circular RNAs (circRNAs) in the mechanism underlying submandibular gland (SMG) dysfunction in hypertension. We employed RNA-seq to analyze the circRNA and mRNA expression profiles of SMGs. Seventy-five differentially expressed (DE) circRNAs and 691 DE mRNAs were determined to be significantly altered in spontaneously hypertensive rats. Altered mRNAs were primarily related to the immune system and immune response. Eight circRNAs were selected for further analysis. Cell adhesion molecules were determined to be the most strongly enriched pathway through analysis of DE mRNAs, the coding noncoding gene co-expression (CNC) network and the competitive endogenous RNA (ceRNA) network. The salivary secretion pathway was observed to be notably enriched through analysis of the ceRNA network. These results suggest that the crosstalk among circRNAs may play a crucial role in the development of SMG dysfunction in hypertension.


Asunto(s)
Hipertensión/metabolismo , ARN Circular/genética , ARN Mensajero/genética , Glándula Submandibular/metabolismo , Animales , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Redes Reguladoras de Genes , Hipertensión/genética , Masculino , ARN Circular/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas SHR , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo
11.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6146-6154, 2022 Nov.
Artículo en Zh | MEDLINE | ID: mdl-36471939

RESUMEN

Since exploding rates of modern mental diseases, application of antidepressants has increased. Worryingly, the antidepressant-induced liver injury has gradually become a serious health burden. Furthermore, since most of the knowledge about antidepressant hepatotoxicity are from pharmacovigilance and clinical case reports and lack of observational studies, the underlying mechanisms are poorly understood and there is a lack of efficient treatment strategies. In this study, antidepressant paroxetine directly triggered inflammasome activation evidenced by caspase-1 activation and downstream effector cytokines interleukin(IL)-1ß secretion. The pretreatment of echinatin, a bioactive component of licorice, completely blocked the activation. This study also found that echinatin effectively inhibited the production of inflammasome-independent tumor necrosis factor α(TNF)-α induced by paroxetine. Mechanistically, the accumulation of mitochondrial reactive oxygen species(mtROS) was a key upstream event of paroxetine-induced inflammasome activation, which was dramatically inhibited by echinatin. In the lipopolysaccharide(LPS)-mediated idiosyncratic drug-induced liver injury(IDILI) model, the combination of LPS and paroxetine triggered aberrant activation of the inflammasome to induce idiosyncratic hepatotoxicity, which was reversed by echinatin pretreatment. Notably, this study also found that various bioactive components of licorice had an inhibitory effect on paroxetine-triggered inflammasome activation. Meanwhile, multiple antidepressant-induced aberrant activation of the inflammasome could be completely blocked by echinatin pretreatment. In conclusion, this study provides a novel insight for mechanism of antidepressant-induced liver injury and a new strategy for the treatment of antidepressant-induced hepatotoxicity.


Asunto(s)
Antidepresivos , Chalconas , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Glycyrrhiza , Paroxetina , Animales , Humanos , Ratones , Antidepresivos/efectos adversos , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/prevención & control , Glycyrrhiza/química , Inflamasomas/efectos de los fármacos , Interleucina-1beta/metabolismo , Lipopolisacáridos/toxicidad , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Paroxetina/efectos adversos , Factor de Necrosis Tumoral alfa , Chalconas/farmacología , Chalconas/uso terapéutico
12.
Phys Chem Chem Phys ; 23(45): 25994-26003, 2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34783808

RESUMEN

To easily synthesize a piezoelectric quantum anomalous Hall insulator (PQAHI), the Janus monolayer Fe2IBr (FeI0.5Br0.5) as a representative PQAHI, is generalized to monolayer FeI1-xBrx (x = 0.25 and 0.75) with α and ß phases. By first-principles calculations, it is proved that monolayer FeI1-xBrx (x = 0.25 and 0.75) are dynamically, mechanically and thermally stable. They are excellent room-temperature PQAHIs with high Curie temperatures, sizable gaps and high Chern number (C = 2). Because the considered crystal structures of α and ß phases possess Mx and My mirror symmetries, the topological properties of monolayer FeI1-xBrx (x = 0.25 and 0.75) are maintained. Namely, if the constructed structures have Mx and My mirror symmetries, the mixing ratio of Br and I atoms can be generalized for other proportions. It is also found that different crystal phases have important effects on the out-of-plane piezoelectric response, and the piezoelectric strain coefficient, d32, of the ß phase is higher than or comparable with those of other known two-dimensional (2D) materials. To further confirm this idea, the physical and chemical properties of monolayer LiFeSe0.75S0.25 with α and ß phases, as a generalization of PQAHI LiFeSe0.5S0.5, is investigated, as it has a similar electronic structure, magnetic and topological properties as LiFeSe0.5S0.5. Our work provides a practical guide to achieve PQAHIs experimentally, and the combination of piezoelectricity, topological and ferromagnetic (FM) orders makes Fe2I2-based monolayers a potential platform for multi-functional spintronics and piezoelectric electronics.

13.
Molecules ; 26(11)2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-34071298

RESUMEN

Chemotherapeutic agents, which contain the Michael acceptor, are potent anticancer molecules by promoting intracellular reactive oxygen species (ROS) generation. In this study, we synthesized a panel of PL (piperlongumine) analogs with chlorine attaching at C2 and an electron-withdrawing/electron-donating group attaching to the aromatic ring. The results displayed that the strong electrophilicity group at the C2-C3 double bond of PL analogs plays an important role in the cytotoxicity whereas the electric effect of substituents, which attached to the aromatic ring, partly contributed to the anticancer activity. Moreover, the protein containing sulfydryl or seleno, such as TrxR, could be irreversibly inhibited by the C2-C3 double bond of PL analogs, and boost intracellular ROS generation. Then, the ROS accumulation could disrupt the redox balance, induce lipid peroxidation, lead to the loss of MMP (Mitochondrial Membrane Potential), and ultimately result in cell cycle arrest and A549 cell line death. In conclusion, PL analogs could induce in vitro cancer apoptosis through the inhibition of TrxR and ROS accumulation.


Asunto(s)
Apoptosis , Dioxolanos/química , Especies Reactivas de Oxígeno , Células A549 , Antineoplásicos/farmacología , Ciclo Celular , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular , Cloro/química , Electrones , Humanos , Peroxidación de Lípido , Potencial de la Membrana Mitocondrial , Oxidación-Reducción , Sales de Tetrazolio/química , Tiazoles/química , Reductasa de Tiorredoxina-Disulfuro/metabolismo
14.
J Cell Mol Med ; 24(14): 7915-7927, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32452125

RESUMEN

Sepsis is the most common cause of death in intensive care units. This study investigated the circular RNA (circRNA) and mRNA expression profiles and functional networks of the aortic tissue in sepsis. We established a lipopolysaccharide (LPS)-induced rat sepsis model. High-throughput sequencing was performed on the aorta tissue to identify differentially expressed (DE) circRNAs and mRNAs, which were validated by real-time quantitative polymerase chain reaction (RT-qPCR). Bioinformatic analysis was carried out and coding and non-coding co-expression (CNC) and competing endogenous RNA (ceRNA) regulatory networks were constructed to investigate the mechanisms. In total, 373 up-regulated and 428 down-regulated circRNAs and 2063 up-regulated and 2903 down-regulated mRNAs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of mRNAs showed that the down-regulated genes were mainly enriched in the process of energy generation. CNC and ceRNA regulatory networks were constructed with seven DE circRNAs. The results of functional enrichment analysis of CNC target genes revealed the important role of circRNAs in inflammatory response. The ceRNA network also highlighted the significant enrichment in calcium signalling pathway. Significant alterations in circRNAs and mRNAs were observed in the aortic tissue of septic rats. In addition, CNC and ceRNA networks were established.


Asunto(s)
Regulación de la Expresión Génica , Redes Reguladoras de Genes , Lipopolisacáridos/efectos adversos , ARN Circular , ARN Mensajero , Sepsis/etiología , Transcriptoma , Animales , Biología Computacional , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , MicroARNs/genética , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados
15.
Cell Mol Neurobiol ; 40(4): 547-554, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31721013

RESUMEN

M1 muscarinic acetylcholine receptors (M1 mAChRs) have long been an attractive target for the treatment of Alzheimer's disease (AD), the most common cause of dementia in the elderly. M1 mAChR agonists show desirably preclinical activities; however, most have not gone further into late clinical trials due to ineffectiveness or side effects. Thus, to understand the signaling pathways involved in M1 mAChR-mediated memory improvement may be important for design of biased agonists with on-target therapeutic effects. M1 mAChRs are classically coupled to Gαq or ectopically to Gαs to activate multiple kinases such as protein kinase C (PKC), Ras and protein kinase A (PKA). Our previous studies have found that M1 mAChRs could improve learning and memory through modulating AMPA receptor GluA1 subunit via PKA-PI3K-Akt signaling. Here, we further investigated whether PKC and Ras were involved in M1 mAChR-mediated modulation of GluA1. We demonstrated the role of PKC and Ras in the signaling pathway, as both PKC inhibitors Ro-31-8425 or Gö6983 and Ras inhibitor salirasib abolished the membrane insertion of GluA1 and enhancement of its phosphorylation at Ser845 induced by M1 mAChRs in the primary cultured neurons and hippocampus in vivo. We further showed that PKC and Ras modulated PKA-PI3K-Akt signaling since the increases of PKA, Akt and mTOR activities by M1 mAChR activation were blocked by PKC and Ras inhibitors. These data demonstrated the detailed mechanism underlying M1 mAChR-mediated modulation of GluA1 through Gαq/11 coupling, broadening the knowledge of the downstream signaling after M1 mAChR-Gαq/11 coupling.


Asunto(s)
Proteína Quinasa C/metabolismo , Receptor Muscarínico M1/metabolismo , Receptores AMPA/metabolismo , Proteínas ras/metabolismo , Animales , Animales Recién Nacidos , Células Cultivadas , Masculino , Ratones Endogámicos C57BL , Modelos Biológicos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Fosfoserina/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Transducción de Señal
16.
Phys Chem Chem Phys ; 22(48): 28359-28364, 2020 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-33300909

RESUMEN

The septuple-atomic-layer VSi2P4 with the same structure of experimentally synthesized MoSi2N4 is predicted to be a spin-gapless semiconductor (SGS) with the generalized gradient approximation (GGA). In this work, the biaxial strain is applied to tune the electronic properties of VSi2P4, and it spans a wide range of properties upon increasing the strain from a ferromagnetic metal (FMM) to SGS to a ferromagnetic semiconductor (FMS) to SGS to a ferromagnetic half-metal (FMHM). Due to broken inversion symmetry, the coexistence of ferromagnetism and piezoelectricity can be achieved in FMS VSi2P4 with the strain range of 0% to 4%. The calculated piezoelectric strain coefficients d11 for 1%, 2% and 3% strains are 4.61 pm V-1, 4.94 pm V-1 and 5.27 pm V-1, respectively, which are greater than or close to a typical value of 5 pm V-1 for bulk piezoelectric materials. Finally, similar to VSi2P4, the coexistence of piezoelectricity and ferromagnetism can be realized by strain in the VSi2N4 monolayer. Our works show that VSi2P4 in the FMS phase with intrinsic piezoelectric properties can have potential applications in spin electronic devices.

17.
Bioorg Chem ; 104: 104273, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32956875

RESUMEN

ß-ionone, a cyclic terpenoid compound present in many fruits, has been showed a broad spectrum of biological activities. In this paper, we synthesized a panel of ß-ionone derivatives and tested their anti-proliferation activity on cancer cell by the MTT assay. The results showed that most of the ß-ionone derivatives were more active than ß-ionone and curcumin. Particularly, the ß-ionone derivatives (1a, 1d and 1g) with ortho-substituents on the aromatic ring exhibited much stronger cytotoxicity than their corresponding meta- and para-substituted compounds. Importantly, the cytotoxicity of the ß-ionone derivatives (1a, 1d and 1g) were relationship with their reactive oxygen species (ROS)-generation abilities, which could lead to the redox imbalance, lipid peroxidation, the loss of mitochondrial membrane potential (MMP), the activation of Bax and Caspase 3, followed by cell apoptosis. This work suggest that the "ortho effect", the ROS-generation ability and drawing fluorine atom into drugs may play a potent role in enhancing the anticancer activity of ß-ionone derivatives.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Norisoprenoides/farmacología , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Norisoprenoides/síntesis química , Norisoprenoides/química , Relación Estructura-Actividad
18.
Angew Chem Int Ed Engl ; 59(31): 13037-13043, 2020 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-32347593

RESUMEN

We investigate a family of dinuclear dysprosium metallocene single-molecule magnets (SMMs) bridged by methyl and halogen groups [Cp'2 Dy(µ-X)]2 (Cp'=cyclopentadienyltrimethylsilane anion; 1: X=CH3 - ; 2: X=Cl- ; 3: X=Br- ; 4: X=I- ). For the first time, the magnetic easy axes of dysprosium metallocene SMMs are experimentally determined, confirming that the orientation of them are perpendicular to the equatorial plane which is made up of dysprosium and bridging atoms. The orientation of the magnetic easy axis for 1 deviates from the normal direction (by 10.3°) due to the stronger equatorial interactions between DyIII and methyl groups. Moreover, its magnetic axes show a temperature-dependent shifting, which is caused by the competition between exchange interactions and Zeeman interactions. Studies of fluorescence and specific heat as well as ab initio calculations reveal the significant influences of the bridging ligands on their low-lying exchange-based energy levels and, consequently, low-temperature magnetic properties.

19.
Opt Express ; 26(21): 27885-27893, 2018 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-30469846

RESUMEN

A simple and low-cost radiative cooler based on one-dimensional photonic crystal is proposed in this work, which has an average emissivity of 96% within the atmospheric transparency window (8-13µm). The ultra-broadband emissivity property is realized by constructing the strongly overlapped optical resonances with a tandem structure composed of two lossy materials while an additional lossless material is adopted as the top layer to reduce the Fresnel reflection of the whole structure. The maximum cooling power density of the fabricated radiative cooler can reach 113.0W/m2 at night. When integrated with an excellent solar reflector that can reflect 97% incident solar power, it theoretically has the maximum cooling power of 83.0 W/m2 in the case of solar irradiance up to 1000 W/m2 at noon.

20.
Ultraschall Med ; 39(5): 526-534, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30176697

RESUMEN

BACKGROUND: Breast lesions classified as BI-RADS-US 3 are probably benign and observation was recommended, while a considerable number of BI-RADS-US 4 lesions were benign, resulting in excessive biopsies. We focus exclusively on BI-RADS-US 3 and 4 lesions and hypothesize that improved diagnostic performance can be achieved by integrating real-time elastography (strain ratio) into the BI-RADS-US classification system. METHOD: From April 2010 to September 2015, 1071 lesions were included in the final analysis. After the conventional ultrasound examination, the BI-RADS-US (2013) classification was used to evaluate the lesions. Then the strain ratios were calculated, and the final diagnosis was made on the basis of histological results. The sensitivity, specificity, accuracy, PPV and NPV were calculated and the AUCs were compared. Additionally, an analysis of the diagnostic performance expressed by the pretest and posttest probability of disease (POD) was performed in BI-RADS-US 3 and 4A lesions. RESULTS: With the cutoff point of 2.98, the sensitivity, specificity and accuracy of the strain ratio method were 86.9 %, 86.6 % and 82.6 %, respectively. In BI-RADS-US 3 lesions, a suspicious strain ratio significantly modified the POD from 1.3 % to a posttest POD of 29.8 %. In BI-RADS-US 4A lesions, a suspicious strain ratio significantly modified the POD from 8.5 % to a posttest POD of 48.7 %. CONCLUSION: Ultrasonographic elastography (strain ratio) yields additional diagnostic information in the evaluation of BI-RADS-US 3 and 4 breast lesions. The strain ratios should be integrated into the BI-RADS-US classification system and into daily practice.


Asunto(s)
Neoplasias de la Mama , Diagnóstico por Imagen de Elasticidad , Neoplasias de la Mama/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Sensibilidad y Especificidad , Ultrasonografía Mamaria
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