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C-natriuretic peptide (CNP) is the central regulator of oocyte meiosis progression, thus coordinating synchronization of oocyte nuclear-cytoplasmic maturation. However, whether CNP can independently regulate cytoplasmic maturation has been long overlooked. Mitochondrial DNA (mtDNA) accumulation is the hallmark event of cytoplasmic maturation, but the mechanism underlying oocyte mtDNA replication remains largely elusive. Herein, we report that CNP can directly stimulate oocyte mtDNA replication at GV stage, and deficiency of follicular CNP may contribute largely to lower mtDNA copy number in in vitro matured oocytes. The mechanistic study showed that cAMP-PKA-CREB1 signaling cascade underlies the regulatory role of CNP in stimulating mtDNA replication and upregulating related genes. Of interest, we also report that CNP-NPR2 signaling is inhibited in aging follicles, and this inhibition is implicated in lower mtDNA copy number in oocytes from aging females. Together, our study provides the first direct functional link between follicular CNP and oocyte mtDNA replication, and identifies its involvement in aging-associated mtDNA loss in oocytes. These findings, not only update the current knowledge of the functions of CNP in coordinating oocyte maturation but also present a promising strategy for improving in vitro fertilization outcomes of aging females.
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DNA Mitocondrial , Técnicas de Maturação in Vitro de Oócitos , Feminino , Humanos , DNA Mitocondrial/genética , Peptídeo Natriurético Tipo C/genética , Peptídeo Natriurético Tipo C/farmacologia , Oócitos/fisiologia , Meiose , Peptídeos Natriuréticos/genética , VasodilatadoresRESUMO
Transition metal dichalcogenides (TMDs) have attracted wide attention due to their quasi-two-dimensional layered structure and exotic properties. Plenty of efforts have been done to modulate the interlayer stacking manner for novel states. However, as an equally important element in shaping the unique properties of TMDs, the effect of intralayer interaction is rarely revealed. Here, we report a particular case of pressure-tuned re-arrangement of intralayer atoms in distorted 1T-NbTe2, which was demonstrated to be a new type of structural phase transition in TMDs. The structural transition occurs in the pressure range of 16-20 GPa, resulting in a transformation of Nb atomic arrangement from the trimeric to dimeric structure, accompanied by a dramatic collapse of unit cell volume and lattice parameters. Simultaneously, a charge density wave (CDW) was also found to collapse during the phase transition. The strong increase in the critical fluctuations of CDW induces a significant decline in the electronic correlation and a change of charge carrier type from hole to electron in NbTe2. Our finding reveals a new mechanism of structure evolution and expands the field of pressure-induced phase transition.
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In situ impedance measurement, resistivity measurements and first-principles calculations have been performed to investigate the effect of high pressure (up to 30.2 GPa) on the metallization and dielectric properties of GaP. It is found that the carrier transport process changes from mixed grain and grain boundary conduction to pure grain conduction at 5.8 GPa, and due to pressure-induced structural phase transition, the resistance drops drastically by three orders of magnitude at 25.5 GPa. Temperature dependence of resistivity measurements and band structure calculations suggest the occurrence of a semiconductor-metal transition. Combining differential charge density and dielectric analysis, it is observed that the electron localization is weakened, which leads to increased polarization and larger relative permittivity in the zb structure. After the phase transition, both the polarization and the relative permittivity decrease. Pressure increases the complex dielectric constant and dielectric loss factor, due to the increase in relaxation polarization and the scattering effect of carriers. Moreover, by comparing the high-pressure behavior of GaP, GaAs and GaSb, the changes in the electronic structure and electric transport process caused by the phase transition can be understood, which can enable us to better understand the metallization behavior and dielectric properties of Ga-based III-V family semiconductors under pressure, and stimulate the design and modification of other related group III-V semiconductors for optoelectronic devices and sensors.
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In this study, oridonin-loaded long-circulating liposomes (LC-lipo@ORI) were prepared with the ethanol injection method. Its physicochemical properties and the morphology were characterized, and its stability and release profiles were evaluated. Furthermore, its antitumor effects were studied using two in vitro cell models of colon cancer and two tumor-bearing models in nude mice. The prepared LC-lipo@ORI was quasi-spherical, with a mean particle size of 109.55 ± 2.30 nm. The zeta potential was -1.38 ± 0.21 mV, the encapsulation efficiency was 85.79%±3.25%, and the drug loading was 5.87%±0.21%. In vitro release results showed that the cumulative release rate of LC-lipo@ORI at 12 h was 63.83%. However, ORI dispersion was almost completely released after 12 h. In vitro cytotoxicity results showed that, the inhibiting effects of LC-lipo@ORI on the proliferation of two types of colon cancer cells were apparently higher than those of ORI dispersion, whereas those of the blank carrier were not noticeable. In vivo studies confirmed that, the encapsulation of LC-lipo enhanced the inhibitory effects of ORI on tumor growth. These results indicated that LC-lipo@ORI a promising formulations for colon cancer treatment.
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Neoplasias do Colo , Diterpenos do Tipo Caurano , Animais , Neoplasias do Colo/tratamento farmacológico , Diterpenos do Tipo Caurano/farmacologia , Lipossomos , Camundongos , Camundongos Nus , Tamanho da PartículaRESUMO
The ionic transport properties of solid electrolyte LaF3 were systematically studied under high pressures up to 30.6 GPa with alternate-current impedance spectra measurements and first-principles calculations. From the impedance spectra measurements, LaF3 was found to transform from pure ionic conduction to mixed ionic and electronic conduction at 15.0 GPa, which results from the pressure-induced structural phase transition from a tysonite-type structure to an anti-Cu3Ti-type structure. F- ion migration can be suppressed by pressure, causing a decrease of the ionic conductivity of LaF3. By first-principles calculations, the pressure-dependent diffusion behaviors of the F- ions can be understood. The increased overlap of electron clouds at the interstitial site between rigid La3+ and liquid F- lattices leads to the appearance of electronic conduction in anti-Cu3Ti-type structured LaF3.
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At ambient conditions, the lattice structure of supported ultrathin transition metal dichalcogenides (TMDs) can be effectively modified by a substrate. When compressed, the effect of substrate is far from settled. In this study, the effects of an Si substrate on the lattice structures of compressed monolayer and multilayer ReS2 were investigated by performing high-pressure Raman measurements and first-principle calculations. Our results revealed substrate-affected strain in compressed monolayer ReS2, which resulted in a distorted unit with S atoms sliding within a single layer. This was evidenced by the split of the Ag-5 mode above 1.7 GPa. However, unlike that of the monolayer ReS2, the Ag-5 mode of multilayer ReS2 remained symmetric up to 4.2 GPa, which can be due to weaker substrate-affected strain in compressed multilayer ReS2 when compared with that in the monolayer ReS2. The noticeably different high-pressure responses between multilayer ReS2 and monolayer ReS2 can be due to the effect of interlayer interactions, and the split of the Ag-5 mode provides a clear indication of the prominent strain in compressed supported ReS2.
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The electrical transport behavior of the superionic conductor AgBr was systematically studied under high pressure up to 30.0 GPa with electrochemical impedance spectra measurements and first-principles calculations. From impedance spectra measurements, a pressure-induced abnormal ionic-polaronic-ionic transition was found. Herein, the ionic to polaronic transition at 5.0 GPa occurs with the absence of a structural phase transition. At 8.6 GPa, the ionic state of AgBr can be reactivated after a structural phase transition. Previous structural studies based on X-ray diffraction data cannot provide strong evidence to support the ionic-polaronic transition in AgBr at 5.0 GPa. In this paper, based on first-principles calculations, a localized-electron-soup model was proposed to explain the physical origin of the ionic-polaronic transition. In this model, more localized electrons around the Br atoms are pressed into interstitial spaces and, simultaneously, polarons are formed between Ag+ ions and the localized electron background at 5.0 GPa. Therefore, the diffusion of Ag+ ions is effectively screened by the movement of the localized electron background from its equilibrium position, much like beans completely trapped in a cup of thick soup.
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Hydride ions (H-) have an appropriate size for fast transport, which makes the conduction of H- attractive. In this work, the H- transport properties of BaH2 have been investigated under pressure using in situ impedance spectroscopy measurements up to 11.2 GPa and density functional theoretical calculations. The H- transport properties, including ionic migration resistance, relaxation frequency, and relative permittivity, change significantly with pressure around 2.3 GPa, which can be attributed to the structural phase transition of BaH2. The ionic migration barrier energy of the P63/mmc phase decreases with pressure, which is responsible for the increased ionic conductivity. A huge dielectric constant at low frequencies is observed, which is related to the polarization of the H- dipoles. The current study establishes general guidelines for developing high-energy storage and conversion devices based on hydride ion transportation.
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We report on the intriguing structural and electrical transport properties of compressed InN. Pronounced anomalies of the resistivity, Hall coefficient, electron concentration, and mobility are observed at â¼11.5 GPa, accompanied by a wurtzite-rocksalt structural transition confirmed using high-pressure XRD measurements and first-principles calculations. The pressure-tuned electrical properties of wurtzite and rocksalt InN are also studied, respectively. Particularly, compression pressure significantly decreases the electron concentration of rocksalt InN by two orders of magnitude and increases the mobility by ten fold. The obvious variations in electrical parameters can be rationalized by our band structure simulations, which reveal a direct-indirect energy crossover at 10 GPa, followed by the rapidly increasing patterns of the energy gap with a pressure coefficient of 33 meV GPa-1. Moreover the electron effective mass and energy gap are found to well satisfy with the k·p model. Definite correlation between the structural change and the electrical transport properties should shed a new light on building InN-based applications in the future.
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In situ impedance measurements were employed to investigate the electrical transport properties of BaMoO4 under pressures of up to 20.0 GPa. Two anomalous changes in the electrical parameters were found, related to the pressure-induced structural phase transitions. The dielectric performance of BaMoO4 was improved by pressure. The dispersion in the real part of dielectric constant versus frequency weakens with increasing pressure. Based on the first-principles calculations, the increases of resistance with increasing pressure in the tetragonal and monoclinic phases were mainly caused by the increasing defect levels. The decrease of the relative permittivity in the tetragonal phase was attributed to pressure-induced strengthening in electronic localization around Mo atoms, which hindered the polarization of Mo-O electric dipoles.
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In this work, we report the pressure-dependent electrical transport and structural properties of SnSe. In our experiments an electronic transition from a semiconducting to semimetallic state was observed at 12.6 GPa, followed by an orthorhombic to monoclinic structural transition. Hall effect measurements indicate that both the carrier concentration and mobility vary abnormally accompanied by the semimetallic electronic transition. First-principles band structure calculations confirm the semiconducting-semimetallic transition, and reveal that the semimetallic character of SnSe can be attributed to the enhanced coupling of Sn-5s, Sn-5p, and Se-3p orbitals under compression that results in the broadening of energy bands and subsequently the closure of the band gap. The pressure modulated variations of electrical transport and structural properties may provide an approach to improving the thermoelectric properties of SnSe.
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Herein, we report on the intriguing electrical transport properties of compressed AlAs. The relative permittivity and the resistances of both the grain and bulk boundaries vary abnormally at â¼10.9 GPa, accompanied by the cubic-hexagonal structural transition of AlAs. With further compression, the boundary effect becomes undistinguished, and subsequently, the electrical transport mechanism converts from boundary- to bulk-dominated, which gives rise to a significant reduction in the total resistance of AlAs. After being quenched to ambient pressure, resistances recover to the initial values followed by the re-emergence of the boundary effect. Eg decreases with pressure and its pressure dependence changes at â¼14.0 GPa, which rationalizes the anomalous variation of the electrical transport properties. The experimental results indicate that the boundary effect can be modulated by compression and increases the resistance difference between the two states. This opens up a new possible basis for optimizing the performance of AlAs-based applications, including multilevel phase-change memories.
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Tin-based perovskite solar cells (Sn-PSCs) without toxic lead ions outperform other types of lead-free PSCs in terms of photovoltaic performance. To avoid the oxidation of Sn2+ cations and the formation of vacancy defects, most reports involve the addition of SnF2 to the perovskite precursor solution, but hybrid tin halide (Sn-PVK) films still suffer from poor crystallinity and stability. In this work, we used an alternative additive of tin trifluoromethanesulfonate (Sn(OTF)2). Compared to SnF2, the solubility of Sn(OTF)2 in the precursor solution is greatly improved, and the crystal nucleation process is delayed, resulting in the enhancement of crystal growth. The coordination ability of the OTF- anions suppresses the oxidation of Sn2+ cations, which promotes the stability of Sn-PVK films. By replacing the conventional additive of SnF2 with Sn(OTF)2, the device achieves an increase in power conversion efficiency from 7.96% to 10.3%, while the stability of the devices is improved simultaneously.
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Lead-free perovskite solar cells with hybrid tin halides (Sn-PVKs) as harvesters have attracted attention with respect to eliminating the contamination of conventional hybrid lead halides. However, Sn-PVK films usually have inferior performance due to rapid crystallization and uncontrollable morphology. Moreover, Sn2+ ions suffer from irreversible oxidation that results in self-doping and device instability. Additive engineering is a key strategy for improving the quality of Sn-PVK films, but solid residues of additives could degrade the transport-recombination process. In this work, dipropyl sulfide (DPS) was introduced as a volatile additive into the precursor solution, and no residue exists in the Sn-PVK films after thermal annealing. The coordinating ability of DPS molecules stabilized Sn2+ ions to form the intermediate complex, which retards the crystallization and oxidation of Sn-PVK films. Consequently, the power conversion efficiencies of devices increase from 11.0% to 12.9% with less recombination and a lower leakage current, and the stability of the devices is improved simultaneously.
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The phase diagram of water near the ice VI-ice VII-liquid triple point and electrical transport properties of these ices have been studied by in situ electrical conductivity measurements in a diamond anvil cell. The obtained phase boundary between ices VI and VII and the melting curve for these ices are in accord with most previous results. The different properties and amount of orientational defects in ice VI and ice VII are associated with abrupt changes in conductivity when a phase transition from ice VI to ice VII occurs. The electrical transport mechanisms of these two ice polymorphs can be understood in terms of the conduction of the already existing ions and Bjerrum defects.
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The measurements of temperature directly influence the reasonability of experiments at high pressure and high temperature. In this article, we proposed a new integration design, the built-in thermocouple, for in situ temperature measurements in high-pressure-high-temperature experiments by fusing the characteristics of thermocouples and diamond anvil cells together. By integrating an S-type thermocouple inside the gasket of a diamond anvil cell, we successfully measured the temperature of the sample straight inside the pressure chamber at high pressure and high temperature. The setup underwent multiple experimental tests using internal and external heating techniques, the results of which revealed its capability to directly characterize the temperature of the sample with comparable accuracy and reliability to that of the typical external thermocouple setup. The proposed setup has also resolved the issue of the discrepancy of temperatures inside and outside the sample chamber and enormously expedited the temperature measurements by significantly reducing the response time of the thermocouple. In conclusion, the built-in thermocouple is a promising approach toward high-efficiency, in situ temperature measurements under extreme conditions.
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In high-pressure experimental methods, sample heating in the pressure chamber of a diamond anvil cell is an important topic, and numerous efforts have been made to improve and develop new technologies. In this paper, we propose a new type of internal resistance heating technique, the composite heating gasket, prepared by integrating an annular heater into the sample chamber for direct heating of the sample. As the effective heating area covers the entire pressure chamber wall, a relatively quasi-uniform temperature field is formed within the sample chamber. At the same time, the integration design reduces the risk of diamond oxidation and enables direct measurement of the spectroscopic properties of samples at high temperatures. The preparation of the composite heating gasket is simple and repeatable, and its heating performance is stable at temperatures above 1400 K. When the sample diameter is 210 µm and no thermal insulation is used, the diameter of the temperature zone in which the temperature difference is less than 10 and 20 K exceeds 120 and 170 µm, respectively. The composite heating gasket represents a significant advancement in providing a uniform temperature field for in situ measurements with diamond anvil cells at high pressure and temperature.
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Clinical and experimental evidence confirmed bacterial infiltration in a variety of tumors, which is related to the progression and therapeutic effects of the tumors. Although the administration of antibiotics inhibits the growth of bacteria inside the tumor, systemic distribution of antibiotics induces an imbalance of other microbiomes in the body, which in turn leads to the development of new diseases. To address this clinical challenge, we nanonized an antibiotic in this study. Metronidazole, an antibiotic against broad anaerobes, was linked to fluorouridine to form an amphiphilic small molecule, metronidazole-fluorouridine, which further autoassembled as metronidazole-fluorouridine nanoparticles (MTI-FDU) in a hydrophilic solution. The disulfide bond in the linker cleaves in response to high levels of glutathione (GSH) in the tumor microenvironment. The synergistic antitumor effect of MTI-FDU was observed in two animal models of gut cancer with intratumoral bacteria. Analysis revealed that metronidazole delivered by nanoparticles attacked bacteria inside the tumor, while it had minimal effect on gut microbial homeostasis. Further experiments at the cellular and molecular levels disclosed that MTI-FDU shaped the tumor immune microenvironment through clearance of bacteria and bacterial products. In conclusion, we achieved a synergistic antitumor effect by a dual target of both the intratumoral microbiome and tumor cells. Antibiotic-composed nanoparticles have a clinical advantage in the treatment of tumors with bacteria infiltration, which kill pro-tumor bacteria efficiently as well as keep a balanced microbiota of the patient.
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Microbiota , Nanopartículas , Neoplasias , Animais , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Antibacterianos/farmacologia , Neoplasias/tratamento farmacológico , Nanopartículas/química , Bactérias , Microambiente TumoralRESUMO
Marine natural product (MNP) entity property information is the basis of marine drug development, and this entity property information can be obtained from the original literature. However, the traditional methods require several manual annotations, the accuracy of the model is low and slow, and the problem of inconsistent lexical contexts cannot be solved well. In order to solve the aforementioned problems, this study proposes a named entity recognition method based on the attention mechanism, inflated convolutional neural network (IDCNN), and conditional random field (CRF), combining the attention mechanism that can use the lexicality of words to make attention-weighted mentions of the extracted features, the ability of the inflated convolutional neural network to parallelize operations and long- and short-term memory, and the excellent learning ability. A named entity recognition algorithm model is developed for the automatic recognition of entity information in the MNP domain literature. Experiments demonstrate that the proposed model can properly identify entity information from the unstructured chapter-level literature and outperform the control model in several metrics. In addition, we construct an unstructured text dataset related to MNPs from an open-source dataset, which can be used for the research and development of resource scarcity scenarios.
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An accurate in situ electrical resistivity measurement of cuprous oxide cubes has been conducted in a diamond anvil cell at room temperature with pressures up to 25 GPa. The abnormal electrical resistivity variation found at 0.7-2.2 GPa is attributed to the phase transformation from a cubic to a tetragonal structure. Three other discontinuous changes in the electrical resistivity are observed around 8.5, 10.3, and 21.6 GPa, corresponding to the phase transitions from tetragonal to pseudocubic to hexagonal to another hexagonal phase, respectively. The first-principles calculations illustrate that the electrical resistivity decrease of the tetragonal phase is not related to band-gap shrinkage but related to a higher quantity of electrons excited from strain-induced states increasing in band gap with increasing pressure. The results indicate that the Cu(2)O cubes begin to crush at about 15 GPa and completely transform into nanocrystalline at 25 GPa.