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1.
Nat Mater ; 23(4): 535-542, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38308087

ABSTRACT

Oxides with a face-centred cubic (fcc) anion sublattice are generally not considered as solid-state electrolytes as the structural framework is thought to be unfavourable for lithium (Li) superionic conduction. Here we demonstrate Li superionic conductivity in fcc-type oxides in which face-sharing Li configurations have been created through cation over-stoichiometry in rocksalt-type lattices via excess Li. We find that the face-sharing Li configurations create a novel spinel with unconventional stoichiometry and raise the energy of Li, thereby promoting fast Li-ion conduction. The over-stoichiometric Li-In-Sn-O compound exhibits a total Li superionic conductivity of 3.38 × 10-4 S cm-1 at room temperature with a low migration barrier of 255 meV. Our work unlocks the potential of designing Li superionic conductors in a prototypical structural framework with vast chemical flexibility, providing fertile ground for discovering new solid-state electrolytes.

2.
Nat Mater ; 22(3): 353-361, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36702887

ABSTRACT

Lithium-rich cathodes are promising energy storage materials due to their high energy densities. However, voltage hysteresis, which is generally associated with transition metal migration, limits their energy efficiency and implementation in practical devices. Here we reveal that voltage hysteresis is related to the collective migration of metal ions, and that isolating the migration events from each other by creating partial disorder can create high-capacity reversible cathode materials, even when migrating transition metal ions are present. We demonstrate this on a layered Li-rich chromium manganese oxide that in its fully ordered state displays a substantial voltage hysteresis (>2.5 V) associated with collective transition metal migration into Li layers, but can be made to achieve high capacity (>360 mAh g-1) and energy density (>1,100 Wh kg-1) when the collective migration is perturbed by partial disorder. This study demonstrates that partially cation-disordered cathode materials can accommodate a high level of transition metal migration, which broadens our options for redox couples to those of mobile cations.

3.
Anesthesiology ; 141(1): 100-115, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38537025

ABSTRACT

BACKGROUND: Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure-lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and antisympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure-lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage. METHODS: In this multicenter, prospective, single-blinded, superiority randomized controlled trial, patients with intracerebral hemorrhage and systolic blood pressure (SBP) 150 mmHg or greater were randomly allocated to the intervention group (a preset protocol with a standard guideline management using remifentanil and dexmedetomidine) or the control group (standard guideline-based management) to receive blood pressure-lowering treatment. The primary outcome was the SBP control rate (less than 140 mmHg) at 1 h posttreatment initiation. Secondary outcomes included blood pressure variability, neurologic function, and clinical outcomes. RESULTS: A total of 338 patients were allocated to the intervention (n = 167) or control group (n = 171). The SBP control rate at 1 h posttreatment initiation in the intervention group was higher than that in controls (101 of 161, 62.7% vs. 66 of 166, 39.8%; difference, 23.2%; 95% CI, 12.4 to 34.1%; P < 0.001). Analysis of secondary outcomes indicated that patients in the intervention group could effectively reduce agitation while achieving lighter sedation, but no improvement in clinical outcomes was observed. Regarding safety, the incidence of bradycardia and respiratory depression was higher in the intervention group. CONCLUSIONS: Among intracerebral hemorrhage patients with a SBP 150 mmHg or greater, a preset protocol using a remifentanil and dexmedetomidine-based standard guideline management significantly increased the SBP control rate at 1 h posttreatment compared with the standard guideline-based management.


Subject(s)
Antihypertensive Agents , Blood Pressure , Cerebral Hemorrhage , Dexmedetomidine , Remifentanil , Humans , Dexmedetomidine/therapeutic use , Dexmedetomidine/administration & dosage , Remifentanil/administration & dosage , Remifentanil/therapeutic use , Male , Female , Prospective Studies , Cerebral Hemorrhage/drug therapy , Aged , Middle Aged , Single-Blind Method , Blood Pressure/drug effects , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/administration & dosage , Treatment Outcome , Hypnotics and Sedatives/therapeutic use
4.
Chem Rev ; 121(3): 1623-1669, 2021 Feb 10.
Article in English | MEDLINE | ID: mdl-33356176

ABSTRACT

The tremendous improvement in performance and cost of lithium-ion batteries (LIBs) have made them the technology of choice for electrical energy storage. While established battery chemistries and cell architectures for Li-ion batteries achieve good power and energy density, LIBs are unlikely to meet all the performance, cost, and scaling targets required for energy storage, in particular, in large-scale applications such as electrified transportation and grids. The demand to further reduce cost and/or increase energy density, as well as the growing concern related to natural resource needs for Li-ion have accelerated the investigation of so-called "beyond Li-ion" technologies. In this review, we will discuss the recent achievements, challenges, and opportunities of four important "beyond Li-ion" technologies: Na-ion batteries, K-ion batteries, all-solid-state batteries, and multivalent batteries. The fundamental science behind the challenges, and potential solutions toward the goals of a low-cost and/or high-energy-density future, are discussed in detail for each technology. While it is unlikely that any given new technology will fully replace Li-ion in the near future, "beyond Li-ion" technologies should be thought of as opportunities for energy storage to grow into mid/large-scale applications.

5.
Bioprocess Biosyst Eng ; 46(9): 1293-1302, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37393574

ABSTRACT

Ionic liquids (ILs) which synthesized from bio-renewable materials have recently attracted much attention for their applications in biocatalysis. Ethyl (R)-3-hydroxybutyrate ((R)-EHB) as a versatile chiral intermediate is of great interest in pharmaceutical synthesis. This study focuses on evaluating the performances of choline chloride (ChCl)-based and tetramethylammonium (TMA)-based neoteric ILs in the efficient synthesis of (R)-EHB via the bioreduction of ethyl acetoacetate (EAA) at high substrate loading by recombinant Escherichia coli cells. It was found that choline chloride/glutathione (ChCl/GSH, molar ratio 1:1) and tetramethylammonium/cysteine ([TMA][Cys], molar ratio 1:1) as eco-friendly ILs not only enhanced the solubility of water-insoluble EAA in the aqueous buffer system, but also appropriately improved the membrane permeability of recombinant E. coli cells, thus boosting catalytic reduction efficiency of EAA to (R)-EHB. In the developed ChCl/GSH- or [TMA][Cys]-buffer systems, the space-time yields of (R)-EHB achieved 754.9 g/L/d and 726.3 g/L/d, respectively, which are much higher than neat aqueous buffer system (537.2 g/L/d space-time yield). Meanwhile, positive results have also been demonstrated in the bioreduction of other prochiral ketones in the established IL-buffer systems. This work exhibits an efficient bioprocess for (R)-EHB synthesis under 325 g/L (2.5 M) substrate loading, and provides promising ChCl/GSH- and [TMA][Cys]-buffer systems employed in the biocatalysis for hydrophobic substrate.


Subject(s)
Ionic Liquids , Ionic Liquids/chemistry , 3-Hydroxybutyric Acid , Escherichia coli/genetics , Water/chemistry , Choline
6.
Nat Mater ; 20(2): 214-221, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33046857

ABSTRACT

High-entropy (HE) ceramics, by analogy with HE metallic alloys, are an emerging class of solid solutions composed of a large number of species. These materials offer the benefit of large compositional flexibility and can be used in a wide variety of applications, including thermoelectrics, catalysts, superionic conductors and battery electrodes. We show here that the HE concept can lead to very substantial improvements in performance in battery cathodes. Among lithium-ion cathodes, cation-disordered rocksalt (DRX)-type materials are an ideal platform within which to design HE materials because of their demonstrated chemical flexibility. By comparing a group of DRX cathodes containing two, four or six transition metal (TM) species, we show that short-range order systematically decreases, whereas energy density and rate capability systematically increase, as more TM cation species are mixed together, despite the total metal content remaining fixed. A DRX cathode with six TM species achieves 307 mAh g-1 (955 Wh kg-1) at a low rate (20 mA g-1), and retains more than 170 mAh g-1 when cycling at a high rate of 2,000 mA g-1. To facilitate further design in this HE DRX space, we also present a compatibility analysis of 23 different TM ions, and successfully synthesize a phase-pure HE DRX compound containing 12 TM species as a proof of concept.

7.
Nat Mater ; 19(10): 1088-1095, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32424371

ABSTRACT

In the synthesis of inorganic materials, reactions often yield non-equilibrium kinetic byproducts instead of the thermodynamic equilibrium phase. Understanding the competition between thermodynamics and kinetics is a fundamental step towards the rational synthesis of target materials. Here, we use in situ synchrotron X-ray diffraction to investigate the multistage crystallization pathways of the important two-layer (P2) sodium oxides Na0.67MO2 (M = Co, Mn). We observe a series of fast non-equilibrium phase transformations through metastable three-layer O3, O3' and P3 phases before formation of the equilibrium two-layer P2 polymorph. We present a theoretical framework to rationalize the observed phase progression, demonstrating that even though P2 is the equilibrium phase, compositionally unconstrained reactions between powder precursors favour the formation of non-equilibrium three-layered intermediates. These insights can guide the choice of precursors and parameters employed in the solid-state synthesis of ceramic materials, and constitutes a step forward in unravelling the complex interplay between thermodynamics and kinetics during materials synthesis.

8.
Faraday Discuss ; 226: 382-408, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33475668

ABSTRACT

Organic aerosols, a major constituent of fine particulate mass in megacities, can be directly emitted or formed from secondary processing of biogenic and anthropogenic volatile organic compound emissions. The complexity of volatile organic compound emission sources, speciation and oxidation pathways leads to uncertainties in the key sources and chemistry leading to formation of organic aerosol in urban areas. Historically, online measurements of organic aerosol composition have been unable to resolve specific markers of volatile organic compound oxidation, while offline analysis of markers focus on a small proportion of organic aerosol and lack the time resolution to carry out detailed statistical analysis required to study the dynamic changes in aerosol sources and chemistry. Here we use data collected as part of the joint UK-China Air Pollution and Human Health (APHH-Beijing) collaboration during a field campaign in urban Beijing in the summer of 2017 alongside laboratory measurements of secondary organic aerosol from oxidation of key aromatic precursors (1,3,5-trimethyl benzene, 1,2,4-trimethyl benzene, propyl benzene, isopropyl benzene and 1-methyl naphthalene) to study the anthropogenic and biogenic contributions to organic aerosol. For the first time in Beijing, this study applies positive matrix factorisation to online measurements of organic aerosol composition from a time-of-flight iodide chemical ionisation mass spectrometer fitted with a filter inlet for gases and aerosols (FIGAERO-ToF-I-CIMS). This approach identifies the real-time variations in sources and oxidation processes influencing aerosol composition at a near-molecular level. We identify eight factors with distinct temporal variability, highlighting episodic differences in OA composition attributed to regional influences and in situ formation. These have average carbon numbers ranging from C5-C9 and can be associated with oxidation of anthropogenic aromatic hydrocarbons alongside biogenic emissions of isoprene, α-pinene and sesquiterpenes.


Subject(s)
Air Pollutants , Particulate Matter , Aerosols/analysis , Air Pollutants/analysis , Beijing , Humans , Mass Spectrometry , Particulate Matter/analysis
9.
Environ Sci Technol ; 55(8): 4542-4552, 2021 04 20.
Article in English | MEDLINE | ID: mdl-33769806

ABSTRACT

Vertical measurements are essential for the characterization of aerosol and boundary layer interactions; yet, our knowledge of vertical profiles of primary and secondary aerosol species in megacities is limited. Here, we conducted comprehensive vertical measurements of aerosol particle composition on a 325 m meteorological tower with two aerosol chemical speciation monitors in winter in urban Beijing. The simultaneous measurements at ground level, 140, and 240 m illustrated similar aerosol bulk composition at these three heights. However, the vertical ratios varied significantly among different aerosol species. Particularly, the vertical ratios of the aqueous phase and photochemical-related secondary organic aerosol (SOA) (aqOOA/OOA) decreased significantly, accompanied by the increases in ratios of secondary to primary OA, highlighting different chemical properties of OA between ground level and aloft, and the large impacts of vertical changes in meteorology and gaseous precursors on SOA formation. The vertical changes in NO3/SO4 ratios, however, were mostly insignificant, likely due to the low relative humidity and aerosol water content that inhibited nocturnal heterogeneous reactions in the residual layer. Considerable increases in the ratios of 240 m to ground level in the early morning were also observed for most aerosol species, demonstrating impact of residual layer on the air pollution of 2nd day.


Subject(s)
Air Pollutants , Aerosols/analysis , Air Pollutants/analysis , Beijing , Environmental Monitoring , Meteorology
10.
Environ Sci Technol ; 55(2): 842-853, 2021 01 19.
Article in English | MEDLINE | ID: mdl-33410677

ABSTRACT

The formation of isoprene nitrates (IsN) can lead to significant secondary organic aerosol (SOA) production and they can act as reservoirs of atmospheric nitrogen oxides. In this work, we estimate the rate of production of IsN from the reactions of isoprene with OH and NO3 radicals during the summertime in Beijing. While OH dominates the loss of isoprene during the day, NO3 plays an increasingly important role in the production of IsN from the early afternoon onwards. Unusually low NO concentrations during the afternoon resulted in NO3 mixing ratios of ca. 2 pptv at approximately 15:00, which we estimate to account for around a third of the total IsN production in the gas phase. Heterogeneous uptake of IsN produces nitrooxyorganosulfates (NOS). Two mono-nitrated NOS were correlated with particulate sulfate concentrations and appear to be formed from sequential NO3 and OH oxidation. Di- and tri-nitrated isoprene-related NOS, formed from multiple NO3 oxidation steps, peaked during the night. This work highlights that NO3 chemistry can play a key role in driving biogenic-anthropogenic interactive chemistry in Beijing with respect to the formation of IsN during both the day and night.


Subject(s)
Hemiterpenes , Nitrates , Aerosols/analysis , Beijing , Butadienes/analysis , Hemiterpenes/analysis , Nitrates/analysis
11.
Indoor Air ; 31(5): 1364-1376, 2021 09.
Article in English | MEDLINE | ID: mdl-33876836

ABSTRACT

Most of human exposure to atmospheric pollutants occurs indoors, and the components of outdoor aerosols may have been changed in the way before reaching indoor spaces. Here we conducted real-time online measurements of mass concentrations and chemical composition of black carbon and the non-refractory species in PM2.5 in an occupied office for approximately one month. The open-close windows and controlled dampness experiments were also performed. Our results show that indoor aerosol species primarily originate from outdoors with indoor/outdoor ratio of these species typically less than unity except for certain organic aerosol (OA) factors. All aerosol species went through filtration upon transport indoors. Ammonium nitrate and fossil fuel OA underwent evaporation or particle-to-gas partitioning, while less oxidized secondary OA (SOA) underwent secondary formation and cooking OA might have indoor sources. With higher particulate matter (PM) mass concentration outdoors than in the office, elevated natural ventilation increased PM exposure indoors and this increased exposure was prolonged when outdoor PM was scavenged. We found that increasing humidity in the office led to higher indoor PM mass concentration particularly more oxidized SOA. Overall, our results highlight that indoor exposure of occupants is substantially different from outdoor in terms of mass concentrations and chemical species.


Subject(s)
Aerosols/analysis , Air Pollutants/analysis , Air Pollution, Indoor/statistics & numerical data , Environmental Monitoring , Cooking , Humans , Humidity , Particle Size , Particulate Matter , Ventilation
13.
Environ Geochem Health ; 41(3): 1617-1633, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30661141

ABSTRACT

To reveal seasonal and spatial variations of heavy metals and metalloids (HMMs) in sediment of the Xiangjiang River, a total of 24 water and 649 sediment samples were collected from six sampling stations in the Songbai section of the river which had been polluted by HMMs for 100 years. Their contamination statuses and ecological risk were determined by enrichment factor (EF), geo-accumulation index (Igeo), pollution load index (PLI), and mean probable effect concentration quotients (mPECQs) analyses. The results revealed a unique seasonal distribution of metals in the sampling stations: The highest concentrations were revealed in the dry seasons (autumn and winter) and the lowest during the wet seasons (spring and summer). It exhibited a greater seasonal variation in the estuary sediment cores (sites ME and MW) than in the cores of other sites. Moreover, the highest concentrations of the tested metals were also found in the estuary sediment cores in the dry seasons (autumn and winter). The highest vertical concentrations of Pb, Zn, Cu, Ni, As, Fe, and Mn were observed at the depths of 16-36 cm in all of the sampled sediment cores. The EF, Igeo, PLI, and mPECQs values of all samples in autumn were higher than in summer. Cd posed the highest ecological risk in all seasons, although its concentrations were lower compared to other studied elements. Our results will benefit to develop feasible sediment quality guidelines for government monitor and remediate the local sediments in the Xiangjiang River.


Subject(s)
Geologic Sediments/analysis , Metalloids/analysis , Metals, Heavy/analysis , Water Pollutants, Chemical/analysis , China , Ecotoxicology/methods , Environmental Monitoring/methods , Estuaries , Principal Component Analysis , Risk Assessment , Rivers , Seasons , Spatio-Temporal Analysis , Water Quality
14.
Cell Physiol Biochem ; 51(5): 2484-2495, 2018.
Article in English | MEDLINE | ID: mdl-30537748

ABSTRACT

BACKGROUND/AIMS: The age-bilirubin-international normalized ratio-creatinine (ABIC) score, which is a predictive model commonly used for alcoholic hepatitis, has not yet been studied in acute-on-chronic hepatitis B liver failure (HBV-ACLF). We aimed to investigate the predictive value of the ABIC score in patients with HBV-ACLF. METHODS: This retrospective study involved 398 patients diagnosed with HBV-ACLF, who were divided into a training cohort of 305 patients and a validation cohort of 93 patients. Univariate and multivariate Cox regression models were used to determine risk factors for mortality. Area under the receiver operating characteristic curve (AUC) was calculated to estimate and compare the predictive values of different prognostic scores. RESULTS: The ABIC score was significantly higher in the death group of the training cohort than in its survival group. Independent risk factors for mortality identified by multivariate Cox analysis included blood urea nitrogen, ABIC score, and Chronic Liver Failure Consortium Organ Failure (CLIF-C OF) score. For predicting 1- and 3-month mortality, AUC was higher for the ABIC score than for the Model for End-stage Liver Diseases (MELD) score (0.732 vs. 0.653, P < 0.05, 0.695 vs. 0.619, P < 0.05, respectively), CLIF-C OF score (0.693, P=0.353, 0.656, P=0.341, respectively), and Child-Pugh score (0.675, P=0.189, 0.656, P=0.300, Respectively). Patients with ABIC score > 9.44 had reduced 1- and 3-month survival rates. CONCLUSION: ABIC score is superior to MELD score in predicting short-term survival in HBV-ACLF patients. ABIC score > 9.44 predicts high short-term mortality risk in HBV-ACLF patients.


Subject(s)
Acute-On-Chronic Liver Failure/blood , Acute-On-Chronic Liver Failure/etiology , Hepatitis B/blood , Hepatitis B/complications , Acute-On-Chronic Liver Failure/diagnosis , Acute-On-Chronic Liver Failure/mortality , Adult , Area Under Curve , Bilirubin/blood , Creatinine/blood , Female , Hepatitis B/diagnosis , Hepatitis B/mortality , Humans , International Normalized Ratio , Male , Middle Aged , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors
15.
Nanotechnology ; 29(9): 09LT01, 2018 Mar 02.
Article in English | MEDLINE | ID: mdl-29313837

ABSTRACT

Generalized-stacking-fault energy (GSFE) serves as an important metric that prescribes dislocation behaviors in materials. In this paper, utilizing first-principle calculations and chemical bonding analysis, we studied the behaviors of generalized stacking fault in graphene and h-BN. It has been shown that the π bond formation plays a critical role in the existence of metastable stacking fault (MSF) in graphene and h-BN lattice along certain slip directions. Chemical functionalization was then proposed as an effective means to engineer the π bond, and subsequently MSF along dislocation slips within graphene and h-BN. Taking hydrogenation as a representative functionalization method, we demonstrated that, with the preferential adsorption of hydrogen along the slip line, π electrons along the slip would be saturated by adsorbed hydrogen atoms, leading to the moderation or elimination of MSF. Our study elucidates the atomic mechanism of MSF formation in graphene-like materials, and more generally, provides important insights towards predictive tuning of mechanic properties in two-dimensional nanomaterials.

16.
Sensors (Basel) ; 18(9)2018 Aug 24.
Article in English | MEDLINE | ID: mdl-30149560

ABSTRACT

There is increasing concern about the health impacts of ambient Particulate Matter (PM) exposure. Traditional monitoring networks, because of their sparseness, cannot provide sufficient spatial-temporal measurements characteristic of ambient PM. Recent studies have shown portable low-cost devices (e.g., optical particle counters, OPCs) can help address this issue; however, their application under ambient conditions can be affected by high relative humidity (RH) conditions. Here, we show how, by exploiting the measured particle size distribution information rather than PM as has been suggested elsewhere, a correction can be derived which not only significantly improves sensor performance but which also retains fundamental information on particle composition. A particle size distribution⁻based correction algorithm, founded on κ -Köhler theory, was developed to account for the influence of RH on sensor measurements. The application of the correction algorithm, which assumed physically reasonable κ values, resulted in a significant improvement, with the overestimation of PM measurements reduced from a factor of ~5 before correction to 1.05 after correction. We conclude that a correction based on particle size distribution, rather than PM mass, is required to properly account for RH effects and enable low cost optical PM sensors to provide reliable ambient PM measurements.

17.
Crit Care Med ; 45(12): e1218-e1225, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28902121

ABSTRACT

OBJECTIVES: Data about the critical care resources in China remain scarce. The purpose of this study was to investigate the variation and distribution of critical care resources in Guangdong province from 2005 to 2015. DESIGN: Data in regard to critical care resources were collected through questionnaires and visits every 5 years from 2005. SETTING: All hospitals in Guangdong province were screened and hospitals that provide critical care services were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: One hundred eleven, 158, and 284 hospitals that provide critical care services were enrolled in the three consecutive surveys respectively. The number of ICUs, ICU beds, intensivists, and nurses increased to 324, 3,956, 2,470, and 7,695, respectively, by 2015. Adjusted by population, the number of ICU beds per 100,000 (100,000) population increased by 147.7% from 2005 to 2015, and the number of intensivists and nurses per 100,000 population increased by 35.3% and 55.1% from 2011 to 2015. However, the numbers in the Pearl River Delta, a richer area, were higher than those in the non-Pearl River Delta area (ICU beds: 4.64 vs 2.58; intensivists: 2.90 vs 1.61; nurses: 9.30 vs 4.71 in 2015). In terms of staff training, only 17.85% of intensivists and 14.29% of nurses have completed a formal accredited critical care training program by 2015. CONCLUSIONS: Our study was the first one to investigate the trend and distribution of critical care resources in China. The quantity of ICU beds and staff has been increasing rapidly, but professional training for staff was inadequate. The distribution of critical care resources was unbalanced. Our study can be beneficial for healthcare policymaking and the allocation of critical care resources in Guangdong province and other provinces in China.


Subject(s)
Critical Care/statistics & numerical data , Intensive Care Units/supply & distribution , China , Equipment and Supplies/supply & distribution , Gross Domestic Product , Hospital Bed Capacity/statistics & numerical data , Humans , Personnel, Hospital/supply & distribution
18.
Artif Organs ; 41(11): E308-E319, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28188657

ABSTRACT

Various research models have been developed to study the biology of disc cells. Recently, the adult disc nucleus pulposus (NP) has been well studied. However, the immature NP is underinvestigated due to a lack of a suitable model. This study aimed to establish an organ culture of immature porcine disc by optimizing culture conditions and using a self-developed substance exchanger-based bioreactor. Immature porcine discs were first cultured in the bioreactor for 7 days at various levels of glucose (low, medium, high), osmolarity (hypo-, iso-, hyper-) and serum (5, 10, 20%) to determine the respective optimal level. The porcine discs were then cultured under the optimized conditions in the novel bioreactor, and were compared with fresh discs at day 14. For high-glucose, iso-osmolarity, or 10% serum, cell viability, the gene expression profile (for anabolic genes and catabolic genes), and glycosaminoglycan (GAG) and hydroxyproline (HYP) contents were more favorable than for other levels of glucose, osmolarity, and serum. When the immature discs were cultured under the optimized conditions using the novel bioreactor for 14 days, the viability of the immature NP was maintained based on histology, cell viability, GAG and HYP contents, and matrix molecule expression. In conclusion, the viability of the immature NP in organ culture could be maintained under the optimized culture conditions (high-glucose, iso-osmolarity, and 10% serum) in the substance exchanger-based bioreactor.


Subject(s)
Bioreactors , Nucleus Pulposus/physiology , Organ Culture Techniques/instrumentation , Regenerative Medicine/instrumentation , Tissue Engineering/instrumentation , Animals , Cell Survival , Culture Media/metabolism , Equipment Design , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Gene Expression Regulation , Glucose/metabolism , Glycosaminoglycans/metabolism , Hydroxyproline/metabolism , Male , Metalloproteases/genetics , Metalloproteases/metabolism , Nucleus Pulposus/cytology , Organ Culture Techniques/methods , Osmolar Concentration , Regenerative Medicine/methods , Sus scrofa , Time Factors , Tissue Engineering/methods
19.
Cell Physiol Biochem ; 39(6): 2216-2226, 2016.
Article in English | MEDLINE | ID: mdl-27832635

ABSTRACT

BACKGROUND/AIMS: Matrix homeostasis within the disc nucleus pulposus (NP) tissue is important for disc function. Increasing evidence indicates that sex hormone can influence the severity of disc degeneration. This study was aimed to study the role of 17ß-estradiol (E2) in NP matrix synthesis and its underlying mechanism. METHODS: Rat NP cells were cultured with (10-5, 10-7 and 10-9 M) or without (control) E2 for48 hours. The estrogen receptor (ER)-ß antagonist PHTPP and ERß agonist ERB 041 were used to investigate the role mediated by ERß. The p38 MAPK inhibitor SB203580 was used to investigate the role of p38 MAPK signaling pathway. Gene and protein expression of SOX9, aggrecan and collagen II, glycosaminoglycan (GAG) content, and immunostaining assay for aggrecan and collagen II were analyzed to evaluate matrix production in rat NP cells. RESULTS: E2 enhanced NP matrix synthesis in a concentration-dependent manner regarding gene and proetin expression of SOX9, aggrecan and collagen II, protein deposition of aggrecan and collagen II, and GAG content. Moreover, activation of p38 MAPK signaling pathway was increased with elevating E2 concentration. Further analysis indicated that ERB 041 and PHTPP could respectively enhance and suppress effects of E2 on matrix synthesis in NP cells, as well as activation of p38 MAPK pathway. Additionally, inhibition of p38 MAPK signaling pathway significantly abolished the effects of E2 on matrix synthesis. CONCLUSION: E2 can enhance matrix synthesis of NP cells and the ERß/p38 MAPK pathway is involved in this regulatory process.


Subject(s)
Estrogen Receptor beta/metabolism , Estrogens/pharmacology , Extracellular Matrix/metabolism , MAP Kinase Signaling System/drug effects , Nucleus Pulposus/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Enzyme Activation/drug effects , Extracellular Matrix/drug effects , Glycosaminoglycans/metabolism , Male , Nucleus Pulposus/drug effects , Rats, Sprague-Dawley , Up-Regulation/drug effects , Up-Regulation/genetics
20.
Stem Cells ; 33(6): 1782-93, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25802002

ABSTRACT

Actl6a (actin-like protein 6A, also known as Baf53a or Arp4) is a subunit shared by multiple complexes including esBAF, INO80, and Tip60-p400, whose main components (Brg1, Ino80, and p400, respectively) are crucial for the maintenance of embryonic stem cells (ESCs). However, whether and how Actl6a functions in ESCs has not been investigated. ESCs originate from the epiblast (EPI) that is derived from the inner cell mass (ICM) in blastocysts, which also give rise to primitive endoderm (PrE). The molecular mechanisms for EPI/PrE specification remain unclear. In this study, we provide the first evidence that Actl6a can protect mouse ESCs (mESCs) from differentiating into PrE. While RNAi knockdown of Actl6a, which appeared highly expressed in mESCs and downregulated during differentiation, induced mESCs to differentiate towards the PrE lineage, ectopic expression of Actl6a was able to repress PrE differentiation. Our work also revealed that Actl6a could interact with Nanog and Sox2 and promote Nanog binding to pluripotency genes such as Oct4 and Sox2. Interestingly, cells depleted of p400, but not of Brg1 or Ino80, displayed similar PrE differentiation patterns. Mutant Actl6a with impaired ability to bind Tip60 and p400 failed to block PrE differentiation induced by Actl6a dysfunction. Finally, we showed that Actl6a could target to the promoters of key PrE regulators (e.g., Sall4 and Fgf4), repressing their expression and inhibiting PrE differentiation. Our findings uncover a novel function of Actl6a in mESCs, where it acts as a gatekeeper to prevent mESCs from entering into the PrE lineage through a Yin/Yang regulating pattern.


Subject(s)
Actins/metabolism , Blastocyst/cytology , Cell Differentiation/physiology , Chromosomal Proteins, Non-Histone/metabolism , DNA-Binding Proteins/metabolism , Endoderm/cytology , Germ Layers/cytology , Mouse Embryonic Stem Cells/cytology , Animals , Cell Lineage/genetics , Gene Expression Regulation, Developmental/physiology , Mice , Octamer Transcription Factor-3/metabolism
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