Recent evidences showed that long noncoding RNAs (lncRNAs) are frequently dysregulated and play important roles in various cancers. Clear cell renal cell carcinoma (ccRCC) is one of the leading cause ...of cancer-related death, largely due to the metastasis of ccRCC. However, the clinical significances and roles of lncRNAs in metastatic ccRCC are still unknown.
lncRNA expression microarray analysis was performed to search the dysregulated lncRNA in metastatic ccRCC. quantitative real-time PCR was performed to measure the expression of lncRNAs in human ccRCC samples. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of lncRNAs on ccRCC cell proliferation, migration, invasion and in vivo metastasis. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and western blot were performed to explore the molecular mechanisms underlying the functions of lncRNAs.
The microarray analysis identified a novel lncRNA termed metastatic renal cell carcinoma-associated transcript 1 (MRCCAT1), which is highly expressed in metastatic ccRCC tissues and associated with the metastatic properties of ccRCC. Multivariate Cox regression analysis revealed that MRCCAT1 is an independent prognostic factor for ccRCC patients. Overexpression of MRCCAT1 promotes ccRCC cells proliferation, migration, and invasion. Depletion of MRCCAT1 inhibites ccRCC cells proliferation, migration, and invasion in vitro, and ccRCC metastasis in vivo. Mechanistically, MRCCAT1 represses NPR3 transcription by recruiting PRC2 to NPR3 promoter, and subsequently activates p38-MAPK signaling pathway.
MRCCAT1 is a critical lncRNA that promotes ccRCC metastasis via inhibiting NPR3 and activating p38-MAPK signaling. Our results imply that MRCCAT1 could serve as a prognostic biomarker and therapeutic target for ccRCC.
Optically active spirocyclic compounds play an important role in drug discovery, and new synthetic strategies for the efficient generation of spiro stereocenters are in much demand. Here we report a ...catalytic enantioselective cycloaddition using spirocyclic donor-acceptor cyclopropanes as a promising approach for the generation of spiro stereocenters. A diastereo- and enantioselective 3 + 3 cycloaddition of spirocyclopropyl oxindoles with both aldonitrones and ketonitrones is developed. The key to reaction development is the activation of spirocyclopropyl oxindoles by a suitable electron-withdrawing N-protecting group. This activation approach offers the promise of a general solution to enable spirocyclopropyl oxindoles as synthons for catalytic enantioselective synthesis of spirocyclic oxindoles featuring a C3 spiro stereocenter, a prominent structural motif in drugs and pharmaceutically active compounds. This protocol also constitutes the catalytic enantioselective reaction using unactivated achiral ketonitrones to construct tetrasubstituted carbon stereocenters.
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•A novel continuous flow aerobic granular reactor was introduced.•Tolerance to organic load by aerobic granules in the reactor was investigated.•Evolution of losing stability of AGS ...was observed.•Cause of the disintegration of the granules was explored.
Sodium acetate as carbon source, tolerance to organic loading rate (OLR) by aerobic granular sludge in a cyclic aerobic granular reactor (CAGR) was investigated by gradually increasing the influent COD. AGS could maintain stability in the continuous flow reactor under OLR⩽15kg/m3d in the former 65days, and SVI, granulation rate, average particle size and water content was 21ml/g, 98%, 1.8mm and 97.2% on the 65th day. However, AGS gradually disintegrated after the 66th day when OLR increased to 18kg/m3d, and granules’ properties deteriorated rapidly in a short time. High removal rates to pollutants were achieved by CAGR in the former 65days, but the removal rates of pollutants dropped sharply from the 66th day. With the increase of OLR and particle size, anaerobic cores inside the granules were formed by massive dead cells, while instability of anaerobic core eventually led to the collapse of the system.
The deformation structure and its contribution to strain hardening of a high manganese austenitic steel were investigated after tensile deformation at 298 K, 77 K and 4 K by means of electron ...backscatter diffraction and transmission electron microscopy, exhibiting a strong dependence of strain hardening and deformation structure on deformation temperature. It was demonstrated that sufficient twinning indeed provides a high and stable strain hardening capacity, leading to a simultaneous increase in strength and ductility at 77 K compared with the tensile deformation at 298 K. Moreover, although the SFE of the steel is ~34.4 mJ/m2 at 4 K, sufficient twinning was not observed, indicating that the mechanical twinning is hard to activate at 4 K. However, numerous planar dislocation arrays and microbands can be observed, and these substructures may be a reason for multi-peak strain hardening behaviors at 4 K. They can also provide certain strain hardening capacity, and a relatively high total elongation of ~48% can be obtained at 4 K. In addition, it was found that the yield strength (YS) and ultimate tensile strength (UTS) linearly increases with the lowering of the deformation temperature from 298 K to 4 K, and the increment in YS and UTS was estimated to be 2.13 and 2.43 MPa per 1 K reduction, respectively.
Tyrosol (Tyr) is a natural antioxidant that displays anti-oxidant and anti-inflammatory properties. The present study aimed to investigate the effect and mechanism of Tyr on lipopolysaccharide ...(LPS)-induced acute lung injury (ALI). In a mouse model, we found that pretreatment with Tyr significantly improved survival rate, attenuated lung permeability, ameliorated histopathological alterations, reduced expression of the inflammatory mediators and improved expression of the antioxidant enzyme. Further study revealed that Tyr markedly inhibited nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activation at both in vivo and in vitro levels. To investigate the underlying mechanism, we examined the impact of Tyr on the heme oxygenase (HO)-1/nuclear factor erythroid-2 related factor 2 (Nrf2) pathway in vivo and in vitro. The results showed that Tyr significantly improved the expression of HO-1 and the activation of Nrf2. This study offers novel evidence to support the efficacy of Tyr against ALI, which helps to clarify the underlying causes of the therapeutic effects behind Tyr.
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•A novel cultivation method for fast aerobic granulation was proposed.•The new method shortened the granulation time to 18days in a pilot scale SBR.•Biological selector was ...implemented to inhibit filamentous bacteria overgrowth.•The inoculated aerobic granules maintained stable and directly as nucleus and carriers for new particles.
Aerobic granular sludge which had good performance to pollutants removal was successfully cultivated within 18days in a pilot scale sequencing batch reactor, about 25% mature aerobic granular sludge was inoculated when the setting time of activated sludge was reduced to 10min. Anaerobic biological selector was implemented to inhibit filamentous bacteria overgrowth, where the maximum COD could reach to 1703.74mg/L. The cultivated aerobic granular sludge was irregular and pale yellow, average particle size, SVI, SV30/SV5, PN/PS, EPS and water content were 1.58mm, 67.64mL/g, 0.91, 2.17, 268.90mgEPS/g MLVSS and 98.16% on the 18th day. Mechanism of rapid granulation mainly included crystal nucleus hypothesis and selection pressure hypothesis. The inoculated aerobic granules could maintain stable under short setting time environment, making it directly as the crystal nucleus and the carriers for new particles without obvious disintegration, which eventually shortened the granulation time greatly.
The Yangtze River estuary is an important ecoregion. However,
Spartina alterniflora, native to North America, was introduced to the estuary in the 1990s through both natural dispersal and humans and ...now it is a dominant species in the estuarine ecosystems, with its invasions leading to multiple consequences to the estuary.
S. alterniflora had great competitive effects on native species, including
Scirpus mariqueter and
Phragmites australis, and could potentially exclude the natives locally. The presence of
S. alterniflora had little influence on the total density of soil nematodes and macrobenthonic invertebrates, but significantly altered the structure of trophic functional groups of nematode and macrobenthonic invertebrate communities. The conversion of mudflats to
Spartina meadows had significant effects on birds of Charadriidae and Scolopacidae, which might be attributable to the reduction of food resources and the physical alterations of habitats for shorebirds.
S. alterniflora invasions increased the primary productivity of the invaded ecosystems, and altered carbon and nitrogen cycling processes. Our studies focused mainly on the effects of
S. alterniflora invasions on the structure of native ecosystems; thus further studies are clearly needed to investigate how ecosystem functioning is affected by the modification of the structure of estuarine ecosystems by
S. alterniflora invasions.
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•A crack propagation was investigated by quasi-in-situ observations at −196 °C.•It was found that the main crack propagates along the {111} planes.•A superior crack propagation ...resistance was comprehensively clarified.
The crack propagation behaviors and microstructure characteristics in the high manganese austenitic steel were comprehensively investigated by quasi-in-situ observations at −196 °C. The steel exhibits a superior fracture toughness at −196 °C than at room temperature. It is found that a severe plastic deformation is necessary for a crack initiation. Although the main crack propagates along the {111} planes due to the plastic strain localization caused by an extensive planar slip, the steel still possesses a superior crack propagation resistance, which is attributed to the activations of multiple twinning and slipping systems, which provide two positive effects on blocking a crack propagation: (1) the plastic deformation further enhanced by multiple twinning and slipping systems as well as (2) a tortuous crack propagation path caused by numerous twin boundaries. Besides, the pronounced deflections at grain boundaries also have a large contribution to block a crack propagation.
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•The addition of 10 at.% Al can effectively suppress the precipitation of (Fe, Mn)23C6.•Increase in grain size benefits the more homogenous and larger- plasticity of the 10%Al ...high-entropy steel.•The 10%Al high-entropy steel with larger grains displays a much higher fracture toughness at 4.2 K.•Twinning, Taylor lattices and deformation bands collectively contribute to the superior mechanical properties of the 10%Al high-entropy steel at 4.2 K.
There exist urgent demands to develop structural materials with superior mechanical properties at 4.2 K. Some high-entropy steels (HESs) show potentials as cryogenic materials, but their deformation behaviors and mechanical properties at 4.2 K have been rarely investigated. Moreover, the aging-induced embrittlement of HESs also severely restricts their applications. In this work, the Fe-Mn-Al-C HESs with different Al contents (0, 4, 10 or 15 at.%) and grain sizes were fabricated, and their deformation behaviors and mechanical properties at 4.2 K were systematically studied. With increasing the Al content, (Fe,Mn)23C6 carbides are effectively inhibited in 10%Al HES after aging at 923 K for 10 days. Therefore, the premature fracture of 10%Al HES is avoided, leading to the excellent combination of high strength (∼1.5 GPa) and high fracture toughness (255 MPa·m1/2) at 4.2 K. The deformation mechanisms shift from the extensive twinning and deformation bands in 0Al HES to the lesser twinning, Taylor lattices and deformation bands in 10%Al HES, which contribute to the high strength and ductility of the 10%Al HES. Furthermore, the 10%Al HES with larger grains displays a much higher fracture toughness at 4.2 K, and this inverse size effect on the cryogenic toughness was elaborately revealed.
To explore the efficacy of high tibial osteotomy （HTO） combined with medial meniscus centralization in knee osteoarthritis.
A total of 26 patients who underwent surgery from October 2018 to October ...2020 were reviewed. Among them, 14 patients underwent high tibial osteotomy combined with arthroscopic meniscus centralization surgery were centralized group, including 8 males and 6 females, with an average age of （50.2±1.4） years old and follow-up time of （16.8±4.0） months. Twelve patients with high tibial osteotomy were in the control group, including 6 males and 6 females, with an average age of （50.9±1.8） years and follow-up time of （19.0±4.8） months. Operation time, the knee Lysholm score, knee 2000 IKDC score, MRI, femoral tibial angle（FTA）, hip knee ankle angle （HKA）, and intraoperative and postoperative complications were recorded.
All the incisions healed without any complication. The operation time in the centralized group was longer than that in the control group（65.0±2.1）min vs（52.0±2.1）min,
<0.05. T
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