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1.
Nature ; 614(7946): 95-101, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36631612

RESUMO

Carbon structures with covalent bonds connecting C60 molecules have been reported1-3, but their production methods typically result in very small amounts of sample, which restrict the detailed characterization and exploration necessary for potential applications. We report the gram-scale preparation of a new type of carbon, long-range ordered porous carbon (LOPC), from C60 powder catalysed by α-Li3N at ambient pressure. LOPC consists of connected broken C60 cages that maintain long-range periodicity, and has been characterized by X-ray diffraction, Raman spectroscopy, magic-angle spinning solid-state nuclear magnetic resonance spectroscopy, aberration-corrected transmission electron microscopy and neutron scattering. Numerical simulations based on a neural network show that LOPC is a metastable structure produced during the transformation from fullerene-type to graphene-type carbons. At a lower temperature, shorter annealing time or by using less α-Li3N, a well-known polymerized C60 crystal forms owing to the electron transfer from α-Li3N to C60. The carbon K-edge near-edge X-ray absorption fine structure shows a higher degree of delocalization of electrons in LOPC than in C60(s). The electrical conductivity is 1.17 × 10-2 S cm-1 at room temperature, and conduction at T < 30 K appears to result from a combination of metallic-like transport over short distances punctuated by carrier hopping. The preparation of LOPC enables the discovery of other crystalline carbons starting from C60(s).

2.
Nature ; 615(7954): 830-835, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36922588

RESUMO

Perovskite light-emitting diodes (LEDs) have attracted broad attention due to their rapidly increasing external quantum efficiencies (EQEs)1-15. However, most high EQEs of perovskite LEDs are reported at low current densities (<1 mA cm-2) and low brightness. Decrease in efficiency and rapid degradation at high brightness inhibit their practical applications. Here, we demonstrate perovskite LEDs with exceptional performance at high brightness, achieved by the introduction of a multifunctional molecule that simultaneously removes non-radiative regions in the perovskite films and suppresses luminescence quenching of perovskites at the interface with charge-transport layers. The resulting LEDs emit near-infrared light at 800 nm, show a peak EQE of 23.8% at 33 mA cm-2 and retain EQEs more than 10% at high current densities of up to 1,000 mA cm-2. In pulsed operation, they retain EQE of 16% at an ultrahigh current density of 4,000 mA cm-2, along with a high radiance of more than 3,200 W s-1 m-2. Notably, an operational half-lifetime of 32 h at an initial radiance of 107 W s-1 m-2 has been achieved, representing the best stability for perovskite LEDs having EQEs exceeding 20% at high brightness levels. The demonstration of efficient and stable perovskite LEDs at high brightness is an important step towards commercialization and opens up new opportunities beyond conventional LED technologies, such as perovskite electrically pumped lasers.

3.
Nature ; 616(7955): 77-83, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37020008

RESUMO

Inorganic superionic conductors possess high ionic conductivity and excellent thermal stability but their poor interfacial compatibility with lithium metal electrodes precludes application in all-solid-state lithium metal batteries1,2. Here we report a LaCl3-based lithium superionic conductor possessing excellent interfacial compatibility with lithium metal electrodes. In contrast to a Li3MCl6 (M = Y, In, Sc and Ho) electrolyte lattice3-6, the UCl3-type LaCl3 lattice has large, one-dimensional channels for rapid Li+ conduction, interconnected by La vacancies via Ta doping and resulting in a three-dimensional Li+ migration network. The optimized Li0.388Ta0.238La0.475Cl3 electrolyte exhibits Li+ conductivity of 3.02 mS cm-1 at 30 °C and a low activation energy of 0.197 eV. It also generates a gradient interfacial passivation layer to stabilize the Li metal electrode for long-term cycling of a Li-Li symmetric cell (1 mAh cm-2) for more than 5,000 h. When directly coupled with an uncoated LiNi0.5Co0.2Mn0.3O2 cathode and bare Li metal anode, the Li0.388Ta0.238La0.475Cl3 electrolyte enables a solid battery to run for more than 100 cycles with a cutoff voltage of 4.35 V and areal capacity of more than 1 mAh cm-2. We also demonstrate rapid Li+ conduction in lanthanide metal chlorides (LnCl3; Ln = La, Ce, Nd, Sm and Gd), suggesting that the LnCl3 solid electrolyte system could provide further developments in conductivity and utility.

4.
Genes Dev ; 31(2): 141-153, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-28167501

RESUMO

Neutrophils are responsible for the first line of defense against invading pathogens. Their nuclei are uniquely structured as multiple lobes that establish a highly constrained nuclear environment. Here we found that neutrophil differentiation was not associated with large-scale changes in the number and sizes of topologically associating domains (TADs). However, neutrophil genomes were enriched for long-range genomic interactions that spanned multiple TADs. Population-based simulation of spherical and toroid genomes revealed declining radii of gyration for neutrophil chromosomes. We found that neutrophil genomes were highly enriched for heterochromatic genomic interactions across vast genomic distances, a process named supercontraction. Supercontraction involved genomic regions located in the heterochromatic compartment in both progenitors and neutrophils or genomic regions that switched from the euchromatic to the heterochromatic compartment during neutrophil differentiation. Supercontraction was accompanied by the repositioning of centromeres, pericentromeres, and long interspersed nuclear elements (LINEs) to the neutrophil nuclear lamina. We found that Lamin B receptor expression was required to attach centromeric and pericentromeric repeats but not LINE-1 elements to the lamina. Differentiating neutrophils also repositioned ribosomal DNA and mininucleoli to the lamina-a process that was closely associated with sharply reduced ribosomal RNA expression. We propose that large-scale chromatin reorganization involving supercontraction and recruitment of heterochromatin and nucleoli to the nuclear lamina facilitates the folding of the neutrophil genome into a confined geometry imposed by a multilobed nuclear architecture.


Assuntos
Diferenciação Celular/genética , Genoma Humano/genética , Neutrófilos/citologia , Cromossomos/genética , Cromossomos/metabolismo , DNA Ribossômico/genética , DNA Ribossômico/metabolismo , Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Células HEK293 , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptor de Lamina B
5.
J Am Chem Soc ; 146(12): 8576-8584, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38488449

RESUMO

Spraying water microdroplets containing 1,2,3-triazole (Tz) has been found to effectively convert gas-phase carbon dioxide (CO2), but not predissolved CO2, into formic acid (FA). Herein, we elucidate the reaction mechanism at the molecular level through quantum chemistry calculations and ab initio molecular dynamics (AIMD) simulations. Computations suggest a multistep reaction mechanism that initiates from the adsorption of CO2 by Tz to form a CO2-Tz complex (named reactant complex (RC)). Then, the RC either is reduced by electrons that were generated at the air-liquid interface of the water microdroplet and then undergoes intramolecular proton transfer (PT) or switches the reduction and PT steps to form a [HCO2-(Tz-H)]- complex (named PC-). Subsequently, PC- undergoes reduction and the C-N bond dissociates to generate COOH- and [Tz-H]- (m/z = 69). COOH- easily converts to HCOOH and is captured at m/z = 45 in mass spectroscopy. Notably, the intramolecular PT step can be significantly lowered by the oriented electric field at the interface and a water-bridge mechanism. The mechanism is further confirmed by testing multiple azoles. The AIMD simulations reveal a novel proton transfer mechanism where water serves as a transporter and is shown to play an important role dynamically. Moreover, the transient •COOH captured by the experiment is proposed to be partly formed by the reaction with H•, pointing again to the importance of the air-water interface. This work provides valuable insight into the important mechanistic, kinetic, and dynamic features of converting gas-phase CO2 to valuable products by azoles or amines dissolved in water microdroplets.

6.
J Am Chem Soc ; 146(15): 10963-10972, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38567839

RESUMO

Microdroplet chemistry is emerging as a great tool for accelerating reactions by several orders of magnitude. Several unique properties such as extreme pHs, interfacial electric fields (IEFs), and partial solvation have been reported to be responsible for the acceleration; however, which factor plays the key role remains elusive. Here, we performed quantum chemical calculations to explore the underlying mechanisms of an aza-Michael addition reaction between methylamine and acrylamide. We showed that the acceleration in methanol microdroplets results from the cumulative effects of several factors. The acidic surface of the microdroplet plays a dominating role, leading to a decrease of ∼9 kcal/mol in the activation barrier. We speculated that the dissociation of both methanol and trace water contributes to the surface acidity. An IEF of 0.1 V/Šcan further decrease the barrier by ∼2 kcal/mol. Partial solvation has a negligible effect on lowering the activation barrier in microdroplets but can increase the collision frequency between reactants. With acidity revealed to be the major accelerating factor for methanol droplets, reactions on water microdroplets should have even higher rates because water is more acidic. Both theoretically and experimentally, we confirmed that water microdroplets significantly accelerate the aza-Michael reaction, achieving an acceleration factor that exceeds 107. This work elucidates the multifactorial influences on the microdroplet acceleration mechanism, and with such detailed mechanistic investigations, we anticipate that microdroplet chemistry will be an avenue rich in opportunities in the realm of green synthesis.

7.
J Am Chem Soc ; 145(48): 26003-26008, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38011046

RESUMO

Even though it is still an emerging field, the application of a high external electric field (EEF) as a green and efficient catalyst in synthetic chemistry has recently received significant attention for the ability to deliver remarkable control of reaction selectivity and acceleration of reaction rates. Here, we extend the application of the EEF to Menshutkin reactions by taking advantage of the spontaneous high electric field at the air-water interfaces of sprayed water microdroplets. Experimentally, a series of Menshutkin reactions were accelerated by 7 orders of magnitude. Theoretically, both density functional theory calculations and ab initio molecular dynamics simulations predict that the reaction barrier decreases significantly in the presence of oriented external electric fields, thereby supporting the notion that the electric fields in the water droplets are responsible for the catalysis. In addition, the ordered solvent and reactant molecules oriented by the electric field alleviate the steric effect of solvents and increase the successful collision rates, thus facilitating faster nucleophilic attack. The success of Menshutkin reactions in this study showcases the great potential of microdroplet chemistry for green synthesis.

8.
Opt Express ; 31(9): 15204-15213, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37157367

RESUMO

We calculate the Casimir interaction between isotropic plates (gold or graphene) and black phosphorus (BP) sheets with Lifshitz theory. It is found that the Casimir force with BP sheets is of the order of α times the perfect metal limit, and α is the fine structure constant. Strong anisotropy of the BP conductivity gives rise to a difference in the Casimir force contribution between the two principal axis. Furthermore, increasing the doping concentration both in BP sheets and graphene sheets can enhance the Casimir force. Moreover, introducing substrate and increased temperature can also enhance the Casimir force, by this way we reveal that the Casimir interaction can be doubled. The controllable Casimir force opens a new avenue for designing next generation devices in micro- and nano-electromechanical systems.

9.
Acta Pharmacol Sin ; 44(11): 2216-2229, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37402997

RESUMO

Excessive fructose consumption increases hepatic de novo lipogenesis, resulting in cellular stress, inflammation and liver injury. Nogo-B is a resident protein of the endoplasmic reticulum that regulates its structure and function. Hepatic Nogo-B is a key protein in glycolipid metabolism, and inhibition of Nogo-B has protective effects against metabolic syndrome, thus small molecules that inhibit Nogo-B have therapeutic benefits for glycolipid metabolism disorders. In this study we tested 14 flavones/isoflavones in hepatocytes using dual luciferase reporter system based on the Nogo-B transcriptional response system, and found that 6-methyl flavone (6-MF) exerted the strongest inhibition on Nogo-B expression in hepatocytes with an IC50 value of 15.85 µM. Administration of 6-MF (50 mg· kg-1 ·d-1, i.g. for 3 weeks) significantly improved insulin resistance along with ameliorated liver injury and hypertriglyceridemia in high fructose diet-fed mice. In HepG2 cells cultured in a media containing an FA-fructose mixture, 6-MF (15 µM) significantly inhibited lipid synthesis, oxidative stress and inflammatory responses. Furthermore, we revealed that 6-MF inhibited Nogo-B/ChREBP-mediated fatty acid synthesis and reduced lipid accumulation in hepatocytes by restoring cellular autophagy and promoting fatty acid oxidation via the AMPKα-mTOR pathway. Thus, 6-MF may serve as a potential Nogo-B inhibitor to treat metabolic syndrome caused by glycolipid metabolism dysregulation.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Flavonas , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Frutose/efeitos adversos , Frutose/metabolismo , Síndrome Metabólica/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Metabolismo dos Lipídeos , Dieta , Lipogênese , Flavonas/farmacologia , Flavonas/uso terapêutico , Flavonas/metabolismo , Ácidos Graxos/metabolismo , Glicolipídeos , Lipídeos
10.
J Integr Plant Biol ; 65(5): 1134-1146, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36647609

RESUMO

Lignin is a major component of plant cell walls and is essential for plant growth and development. Lignin biosynthesis is controlled by a hierarchical regulatory network involving multiple transcription factors. In this study, we showed that the gene encoding an APETALA 2/ethylene-responsive element binding factor (AP2/ERF) transcription factor, PagERF81, from poplar 84 K (Populus alba × P. glandulosa) is highly expressed in expanding secondary xylem cells. Two independent homozygous Pagerf81 mutant lines created by gene editing, produced significantly more but smaller vessel cells and longer fiber cells with more lignin in cell walls, while PagERF81 overexpression lines had less lignin, compared to non-transgenic controls. Transcriptome and reverse transcription quantitative PCR data revealed that multiple lignin biosynthesis genes including Cinnamoyl CoA reductase 1 (PagCCR1), Cinnamyl alcohol dehydrogenase 6 (PagCAD6), and 4-Coumarate-CoA ligase-like 9 (Pag4CLL9) were up-regulated in Pagerf81 mutants, but down-regulated in PagERF81 overexpression lines. In addition, a transient transactivation assay revealed that PagERF81 repressed the transcription of these three genes. Furthermore, yeast one hybrid and electrophoretic mobility shift assays showed that PagERF81 directly bound to a GCC sequence in the PagCCR1 promoter. No known vessel or fiber cell differentiation related genes were differentially expressed, so the smaller vessel cells and longer fiber cells observed in the Pagerf81 lines might be caused by abnormal lignin deposition in the secondary cell walls. This study provides insight into the regulation of lignin biosynthesis, and a molecular tool to engineer wood with high lignin content, which would contribute to the lignin-related chemical industry and carbon sequestration.


Assuntos
Lignina , Populus , Lignina/metabolismo , Populus/metabolismo , Xilema/metabolismo , Madeira/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Diferenciação Celular , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/metabolismo
12.
Angew Chem Int Ed Engl ; 62(22): e202302036, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-36950947

RESUMO

Developing porous sorbents represents a potential energy-efficient way for industrial gas separation. However, a bottleneck for reducing the energy penalty is the trade-off between dynamic adsorption capacity and selectivity. Herein, we showed this problem can be overcome by modulating the kinetic and thermodynamic separation behaviours in metal-organic frameworks for sieving 2-butene geometric isomers, which are desired for upgrading the raffinates to higher value-added end products. We found that the iron-triazolate framework can realize the selective shape screening of 2-butene isomers assisted by electrostatic interactions at the pore apertures. Further introducing uncoordinated N binding sites by ligand substitution lowered the gas diffusion barrier and greatly boosted the dynamic separation performance. In breakthrough tests under ambient conditions, trans-2-C4 H8 can be efficiently separated from cis-2-C4 H8 with a record capacity of 2.10 mmol g-1 with high dynamic selectivity of 2.39.

13.
Am J Respir Cell Mol Biol ; 66(5): 555-563, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35157553

RESUMO

Acute respiratory distress syndrome (ARDS) remains a significant problem in need of new pharmaceutical approaches to improve its resolution. Studies comparing gene expression signatures in rodents and humans with lung injury reveal conserved pathways, including MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-related protein kinase) activation. In preclinical acute lung injury (ALI) models, inhibition of MAP2K1 (MAPK kinase 1)/MAP2K2 (MAPK kinase 2) improves measures of ALI. Myeloid cell deletion of MAP2K1 results in sustained MAP2K2 activation and nonresolving ALI, suggesting that MAP2K2 deactivation may be a key driver of ALI resolution. We used human genomic data from the iSPAAR (Identification of SNPs Predisposing to Altered Acute Lung Injury Risk) Consortium to assess genetic variants in MAP2K1 and MAP2K2 for association with mortality from ARDS. To determine the role of MAP2K2 in ALI recovery, we studied mice deficient in Map2k2 (Mek2-/-) and wild-type control mice in ALI models. We identified a MAP2K2 variant that was associated with death in ARDS and MAP2K2 expression. In Pseudomonas aeruginosa ALI, Mek2-/- mice had similar early alveolar neutrophilic recruitment but faster resolution of alveolar neutrophilia and vascular leak. Gene expression analysis revealed a role for MAP2K2 in promoting and sustaining select proinflammatory pathway activation in ALI. Bone marrow chimera studies indicate that leukocyte MAP2K2 is the key regulator of ALI duration. These studies implicate a role for MAP2K2 in ALI duration via transcriptional regulation of inflammatory programming with potential relevance to ARDS. Targeting leukocyte MAP2K2 may be an effective strategy to promote ALI resolution.


Assuntos
Lesão Pulmonar Aguda , MAP Quinase Quinase 2/metabolismo , Síndrome do Desconforto Respiratório , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica , MAP Quinase Quinase 2/genética , Camundongos , Síndrome do Desconforto Respiratório/genética
14.
J Am Chem Soc ; 144(4): 1634-1646, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35014789

RESUMO

The rational design and controllable synthesis of hollow nanoparticles with both a mesoporous shell and an asymmetric architecture are crucially desired yet still significant challenges. In this work, a kinetics-controlled interfacial super-assembly strategy is developed, which is capable of preparing asymmetric porous and hollow carbon (APHC) nanoparticles through the precise regulation of polymerization and assembly rates of two kinds of precursors. In this method, Janus resin and silica hybrid (RSH) nanoparticles are first fabricated through the kinetics-controlled competitive nucleation and assembly of two precursors. Specifically, silica nanoparticles are initially formed, and the resin nanoparticles are subsequently formed on one side of the silica nanoparticles, followed by the co-assembly of silica and resin on the other side of the silica nanoparticles. The APHC nanoparticles are finally obtained via high-temperature carbonization of RSH nanoparticles and elimination of silica. The erratic asymmetrical, hierarchical porous and hollow structure and excellent photothermal performance under 980 nm near-infrared (NIR) light endow the APHC nanoparticles with the ability to serve as fuel-free nanomotors with NIR-light-driven propulsion. Upon illumination by NIR light, the photothermal effect of the APHC shell causes both self-thermophoresis and jet driving forces, which propel the APHC nanomotor. Furthermore, with the assistance of phase change materials, such APHC nanoparticles can be employed as smart vehicles that can achieve on-demand release of drugs with a 980 nm NIR laser. As a proof of concept, we apply this APHC-based therapeutic system in cancer treatment, which shows improved anticancer performance due to the synergy of photothermal therapy and chemotherapy. In brief, this kinetics-controlled approach may put forward new insight into the design and synthesis of functional materials with unique structures, properties, and applications by adjusting the assembly rates of multiple precursors in a reaction system.

15.
Plant Physiol ; 186(1): 388-406, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-33599732

RESUMO

Ethiopian mustard (Brassica carinata) in the Brassicaceae family possesses many excellent agronomic traits. Here, the high-quality genome sequence of B. carinata is reported. Characterization revealed a genome anchored to 17 chromosomes with a total length of 1.087 Gb and an N50 scaffold length of 60 Mb. Repetitive sequences account for approximately 634 Mb or 58.34% of the B. carinata genome. Notably, 51.91% of 97,149 genes are confined to the terminal 20% of chromosomes as a result of the expansion of repeats in pericentromeric regions. Brassica carinata shares one whole-genome triplication event with the five other species in U's triangle, a classic model of evolution and polyploidy in Brassica. Brassica carinata was deduced to have formed ∼0.047 Mya, which is slightly earlier than B. napus but later than B. juncea. Our analysis indicated that the relationship between the two subgenomes (BcaB and BcaC) is greater than that between other two tetraploid subgenomes (BjuB and BnaC) and their respective diploid parents. RNA-seq datasets and comparative genomic analysis were used to identify several key genes in pathways regulating disease resistance and glucosinolate metabolism. Further analyses revealed that genome triplication and tandem duplication played important roles in the expansion of those genes in Brassica species. With the genome sequencing of B. carinata completed, the genomes of all six Brassica species in U's triangle are now resolved. The data obtained from genome sequencing, transcriptome analysis, and comparative genomic efforts in this study provide valuable insights into the genome evolution of the six Brassica species in U's triangle.


Assuntos
Evolução Biológica , Brassica/genética , Genoma de Planta , Poliploidia , Modelos Biológicos
16.
Reprod Biol Endocrinol ; 20(1): 32, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35177076

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. The mechanism by which circular RNA (circRNA) drives PCOS development remains unclear. Thus, the study is designed to explore the role of a novel circRNA, circ_FURIN, in the PCOS cell model and the underlying mechanism. METHODS: PCOS cell model was established by treating human ovarian granulosa-like tumor cells (KGN) with Testosterone (TTR). RNA expressions of circ_FURIN, microRNA-423-5p (miR-423-5p) and myotubularin 1 (MTM1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was checked by Western blot. Cell proliferation was investigated by a 5-Ethynyl-29-deoxyuridine assay, 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis for cell cycle. Apoptotic cells were quantified by flow cytometry analysis for cell apoptosis. The interplay between miR-423-5p and circ_FURIN or MTM1 was identified by dual-luciferase reporter and RNA pull-down assays. RESULTS: Circ_FURIN and MTM1 expressions were significantly upregulated, whereas miR-423-5p was downregulated in the ovarian cortex tissues of PCOS patients and TTR-treated KGN cells compared with controls. Circ_FURIN depletion relieved TTR-induced proliferation inhibition and apoptosis promotion. Besides, knockdown of miR-423-5p, a target miRNA of circ_FURIN, rescued circ_FURIN knockdown-mediated effects under TTR treatment. MiR-423-5p remitted TTR-induced cell disorders by binding to MTM1. Moreover, circ_FURIN modulated MTM1 expression through miR-423-5p. CONCLUSION: Circ_FURIN silencing protected against TTR-induced dysfunction by the miR-423-5p/MTM1 pathway in human ovarian granulosa-like tumor cells.


Assuntos
Tumor de Células da Granulosa/genética , MicroRNAs/genética , Síndrome do Ovário Policístico/genética , Proteínas Tirosina Fosfatases não Receptoras/genética , RNA Circular/genética , Apoptose/genética , Proliferação de Células/genética , Células Cultivadas , Feminino , Furina/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Tumor de Células da Granulosa/induzido quimicamente , Tumor de Células da Granulosa/patologia , Humanos , Modelos Biológicos , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , RNA Circular/fisiologia , Testosterona/efeitos adversos
17.
J Surg Res ; 279: 682-691, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35940046

RESUMO

INTRODUCTION: Histologic characteristics cannot adequately predict which patients are at risk of developing metastatic disease after excision of primary cutaneous melanoma. The aim of this study was to identify immunomodulatory genes in primary tumors associated with development of distant metastases. MATERIALS AND METHODS: Thirty-seven patients with primary melanoma underwent surgical excision. RNA was extracted from the primary tumor specimens. cDNA was synthesized and used with Human Gene Expression microarray. Differential expression of 74 immunomodulatory genes was compared between patients who developed distant metastases and those who did not. RESULTS: Six of 37 patients developed distant metastases during the time of the study. Differential expression of microarray data showed upregulation of four immunomodulatory genes in this group. These four genes-c-CBL, CD276, CXCL1, and CXCL2-were all significantly overexpressed in the metastatic group with differential expression fold change of 1.15 (P = 0.01), 1.16 (P = 0.04), 2.51 (P < 0.001), and 1.68 (P < 0.02), respectively. CXCL1 had particularly high predictive value with an area under the curve of 0.80. Multivariate analysis showed only expression of CXCL1 (P = 0.01) remains predictive of distant metastases in melanoma patients. This result was confirmed using quantitative real-time polymerase chain reaction. CONCLUSIONS: CXCL1, CXCL2, c-CBL, and CD276 are immunomodulatory genes present in primary melanoma that are strongly associated with development of metastatic disease. Identification of their presence, particularly CXCL1, in the primary tumor could be used as a predictor of future risk of metastatic disease and thereby to identify patients who might benefit early from immunotherapy.


Assuntos
Melanoma , Neoplasias Cutâneas , Antígenos B7 , DNA Complementar , Humanos , Metástase Linfática , Melanoma/patologia , RNA , Neoplasias Cutâneas/patologia
18.
J Nanobiotechnology ; 20(1): 50, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35078498

RESUMO

BACKGROUND: Although cisplatin-based chemotherapy has been used as the first-line treatment for ovarian cancer (OC), tumor cells develop resistance to cisplatin during treatment, causing poor prognosis in OC patients. Studies have demonstrated that overactivation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is involved in tumor chemoresistance and that overexpression of microRNA-497 (miR497) may overcome OC chemotherapy resistance by inhibiting the mTOR pathway. However, the low transcriptional efficiency and unstable chemical properties of miR497 limit its clinical application. Additionally, triptolide (TP) was confirmed to possess a superior killing effect on cisplatin-resistant cell lines, partially through inhibiting the mTOR pathway. Even so, the clinical applications of TP are restricted by serious systemic toxicity and weak water solubility. RESULTS: Herein, whether the combined application of miR497 and TP could further overcome OC chemoresistance by synergically suppressing the mTOR signaling pathway was investigated. Bioinspired hybrid nanoparticles formed by the fusion of CD47-expressing tumor exosomes and cRGD-modified liposomes (miR497/TP-HENPs) were prepared to codeliver miR497 and TP. In vitro results indicated that the nanoparticles were efficiently taken up by tumor cells, thus significantly enhancing tumor cell apoptosis. Similarly, the hybrid nanoparticles were effectively enriched in the tumor areas and exerted significant anticancer activity without any negative effects in vivo. Mechanistically, they promoted dephosphorylation of the overactivated PI3K/AKT/mTOR signaling pathway, boosted reactive oxygen species (ROS) generation and upregulated the polarization of macrophages from M2 to M1 macrophages. CONCLUSION: Overall, our findings may provide a translational strategy to overcome cisplatin-resistant OC and offer a potential solution for the treatment of other cisplatin-resistant tumors.


Assuntos
Exossomos , MicroRNAs , Nanopartículas , Neoplasias Ovarianas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Diterpenos , Resistencia a Medicamentos Antineoplásicos , Compostos de Epóxi , Exossomos/metabolismo , Humanos , Lipossomos/farmacologia , MicroRNAs/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Fenantrenos , Fosfatidilinositol 3-Quinases/metabolismo
19.
BMC Musculoskelet Disord ; 23(1): 914, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36242007

RESUMO

PURPOSE: Restoration of the segment lordosis angle (SLA) can effectively reduce the risk of adjacent segment degeneration. This study aimed to perform a comprehensive multifactor analysis of the risk factors affecting restoration and maintenance of the SLA in oblique lumbar interbody fusion (OLIF). METHODS: Seventy-three patients (93 segments) who underwent OLIF with posterior pedicle screw fixation due to lumbar degenerative disease between January 2015 and December 2019 were included. Radiographic parameters including the middle disc height (MDH), segment lordosis angle (SLA), cage center point ratio (CPR), cage subsidence, and L1 CT Hounsfield Unit (HU) were measured. RESULTS: The postoperative SLA increased from 3.5° to 8.7°, and decreased to 6.7° at the last follow-up. Multivariate analysis showed that preoperative SLA, CPR and cage subsidence were significantly correlated with SLA restoration. The significant correlations were between restoration of SLA with pre-operative SLA (r=-0.575, adjusted R2 = 0.323, P < 0.01) and between SLA restoration and CPR (r = 0.526, adjusted R2 = 0.268, P < 0.01). Cage subsidence was found in 12.9% (12/93) of segments and was the main factor affecting SLA loss (4.2 ± 1.0° versus 1.7 ± 2.1°, P < 0.01). Logistic regression analysis showed that CPR < 50%, L1 CT HU < 110 and cage height > preoperative MDH were risk factors for cage subsidence. Cages placed anteriorly (CPR ≥ 50%) showed a large SLA increase and lower incidence of cage subsidence than those placed posteriorly (5.9 ± 3.9° versus 4.2 ± 3.2°, P < 0.05; 1.8% versus 28.9%, P < 0.05, respectively). CONCLUSION: SLA restoration is dependent on preoperative SLA, cage subsidence and cage position in OLIF. Cage position is the key determinant of SLA restoration and placement of the cage at the anterior position (CPR ≥ 50%) can achieve better restoration of the SLA and reduce the incidence of cage subsidence.


Assuntos
Lordose , Fusão Vertebral , Humanos , Lordose/diagnóstico por imagem , Lordose/etiologia , Lordose/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Região Lombossacral , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
20.
Angew Chem Int Ed Engl ; 61(25): e202202912, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35384234

RESUMO

Covalent organic frameworks (COFs) featuring permanent porosity, designable topologies, and tailorable functionalities have attracted great interest in the past two decades. Developing efficient modular approaches to rationally constructing COFs from a set of molecules via covalent linking has been long pursued. Herein, we report a facile one-pot strategy to prepare COFs via an irreversible Suzuki coupling reaction followed by a reversible Schiff's base reaction without the need for intermediate isolation. Gram-scale ordered frameworks with kgm topology and rich porosities can be obtained by using diamino-aryl halide and dialdehyde aryl-borate compounds as monomers. The resultant microporous CR-COFs were used for efficient C2 H4 /C3 H6 separation. This strategy reduces the waste generated and efforts consumed by stepwise reactions and relative purification processes, making the large-scale syntheses of stable COFs feasible. Moreover, it offers a novel modular approach to designing COF materials.

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