Hepatic stellate cells (HSCs) are activated by inflammatory mediators to secrete extracellular matrix for collagen deposition, leading to liver fibrosis. Ferroptosis is iron- and lipid ...hydroperoxide-dependent programmed cell death, which has recently been targeted for inhibiting liver fibrogenic processes. Tripartite motif-containing protein 26 (TRIM26) is an E3 ubiquitin ligase that functions as a tumor suppressor in hepatocellular carcinoma, while little is known about its function in liver fibrosis. In the present study, the differential expression of TRIM26 in normal and fibrotic liver tissues was examined based on both online databases and specimens collected from patient cohort. The effects of TRIM26 on HSCs ferroptosis were examined
through evaluating cell proliferation, lipid peroxidation, and expression of key ferroptosis-related factors.
function of TRIM26 in liver fibrosis was examined based on CCl
-induced mice model. We found that TRIM26 was downregulated in fibrotic liver tissues. The overexpression of
inhibited HSCs proliferation, promoted lipid peroxidation, manipulated ferroptosis-related factor expressions, and counteracted the effect of iron inhibitor deferoxamine. Moreover, TRIM26 physically interacted with solute carrier family-7 member-11 (SLC7A11), a critical protein for lipid reactive oxygen species (ROS) scavenging, and mediated its ubiquitination. In addition,
overexpression induced HSCs ferroptosis and mitigated CCl
-induced liver fibrosis in mice. In conclusion, TRIM26 promotes HSCs ferroptosis to suppress liver fibrosis through mediating the ubiquitination of SLC7A11. The TRIM26-targeted SLC7A11 suppression can be a novel therapeutic strategy for liver fibrosis.
Accumulating evidence suggests that autophagy is closely related to the pathogenesis of osteoarthritis (OA). The aim of this study was to determine the changes in autophagy during the progression of ...OA and to elucidate the specific role of autophagy in OA. For this purpose, a cellular model of OA was generated by stimulating SW1353 cells with interleukin (IL)-1β and a rabbit model of OA was also established by an intra-articular injection of collagenase, followed by treatment with the autophagy specific inhibitor, 3-methyladenine (3-MA). Cell viability was analyzed by MTS assay, and the mRNA expression levels of matrix metalloproteinases (MMP)-13 and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by RT-qPCR. Cartilage degeneration was examined under a light microscope, and autophagosome and chondrocyte degeneration was observed by transmission electron microscopy. The protein expression of Beclin-1 and light chain 3 (LC3)B was evaluated by western blot analysis and immunofluorescence staining. We found that the autophagy was enhanced during the early stages and was weakened during the late stages of experimental OA. The inhibition of autophagy by 3-MA significantly aggravated the degeneration of chondrocytes and cartilage in experimental OA. Our results thus determine the changes in autophagy during different stages of OA, as well as the role of impaired autophagy in the development of OA. Our data suggest that the regulation of autophagy may be a potential therapeutic strategy with which to attenuate OA.
Autonomous vehicles can obtain real-time road information using 3D sensors. With road information, vehicles avoid obstacles through real-time path planning to improve their safety and stability. ...However, most of the research on driverless vehicles have been carried out on urban even driveways, with little consideration of uneven terrain. For an autonomous full tracked vehicle (FTV), the uneven terrain has a great impact on the stability and safety. In this paper, we proposed a method to predict the pose of the FTV based on accurate road elevation information obtained by 3D sensors. If we could predict the pose of the FTV traveling on uneven terrain, we would not only control the active suspension system but also change the driving trajectory to improve the safety and stability. In the first, 3D laser scanners were used to get real-time cloud data points of the terrain for extracting the elevation information of the terrain. Inertial measurement units (IMUs) and GPS are essential to get accurate attitude angle and position information. Then, the dynamics model of the FTV was established to calculate the vehicle's pose. Finally, the Kalman filter was used to improve the accuracy of the predicted pose. Compared to the traditional method of driverless vehicles, the proposed approach was more suitable for autonomous FTV. The real-world experimental result demonstrated the accuracy and effectiveness of our approach.
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We reconstructed the Holocene climate in the study area using data from a BZ section in the Baiyangdian paleo-lake. Samples were analyzed for multiple proxies for climate conditions, including grain ...size, magnetic susceptibility (MS), and carbonate content, which were combined with accelerator mass spectrometry (AMS)
14
C data. The results show that from 10.0 to 6.3 kyr BP, the study area experienced an interval of increasing precipitation and rising water level at Lake Baiyangdian. For a very short period, ~ 8.4 kyr BP, the extent of the lake reached the sampling point. The climate during this stage was relatively humid. The water level dropped abruptly at 6.5 kyr BP as a result of a weak monsoon event. From 6.3 to 2.9 kyr BP the climate became humid once again. The continuous lacustrine sediment of the strata indicated that the water level of Lake Baiyangdian expanded rapidly during this period and reached the sampling point. After 2.9 kyr BP, the climate in the region changed again from humid to dry. The abrupt increase in MS after ~1 kyr BP (993 AD) is consistent with records of human activities in local chronicles, which indicates that the environment in the study area was influenced by human activities. Through a comparison of the BZ section and the East Asian summer monsoon (EASM) records, we found that precipitation in the study area was controlled by the EASM. A series of cold Holocene events were clearly recorded by the sediment in the BZ section, and these events are synchronous with the North Atlantic ice-rafting events (IRD). The connection between the characteristics of the BZ section and the EASM and IRD indicate that climate evolution in the study area was strongly affected by EASM and IRD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The vertebrate-specific proteins astrotactin-1 and 2 (ASTN-1 and ASTN-2) are integral membrane perforin-like proteins known to play critical roles in neurodevelopment, while ASTN-2 has been linked to ...the planar cell polarity pathway in hair cells. Genetic variations associated with them are linked to a variety of neurodevelopmental disorders and other neurological pathologies, including an advanced onset of Alzheimer's disease. Here we present the structure of the majority endosomal region of ASTN-2, showing it to consist of a unique combination of polypeptide folds: a perforin-like domain, a minimal epidermal growth factor-like module, a unique form of fibronectin type III domain and an annexin-like domain. The perforin-like domain differs from that of other members of the membrane attack complex-perforin (MACPF) protein family in ways that suggest ASTN-2 does not form pores. Structural and biophysical data show that ASTN-2 (but not ASTN-1) binds inositol triphosphates, suggesting a mechanism for membrane recognition or secondary messenger regulation of its activity. The annexin-like domain is closest in fold to repeat three of human annexin V and similarly binds calcium, and yet shares no sequence homology with it. Overall, our structure provides the first atomic-resolution description of a MACPF protein involved in development, while highlighting distinctive features of ASTN-2 responsible for its activity.
As a substitute for toxic cadmium coatings in the aerospace industry, zinc-nickel coatings have excellent application prospects, and their properties can be improved by adding molybdenum. In this ...study, laser-assisted electrodeposition is used to improve the surface quality and properties of Zn–Ni–Mo coatings, with investigation of how laser energy in the range of 0–21.1 μJ affects their element content, surface morphology, crystal phase, microhardness, residual internal stress, and corrosion resistance. The laser irradiation accelerates the electrodeposition, refines the grain size, improves the hydrogen adsorption, and reduces the residual tensile stress, and a laser energy of 15.4 μJ gives the highest Ni and Mo contents and the lowest Zn content, as well as the optimum surface morphology, microhardness, residual internal stress, and corrosion resistance of the coating.
Abstract
Carboxysomes are a family of bacterial microcompartments in cyanobacteria and chemoautotrophs. They encapsulate Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic ...anhydrase catalyzing carbon fixation inside a proteinaceous shell. How Rubisco complexes pack within the carboxysomes is unknown. Using cryo-electron tomography, we determine the distinct 3D organization of Rubisco inside two distant α-carboxysomes from a marine α-cyanobacterium
Cyanobium
sp. PCC 7001 where Rubiscos are organized in three concentric layers, and from a chemoautotrophic bacterium
Halothiobacillus neapolitanus
where they form intertwining spirals. We further resolve the structures of native Rubisco as well as its higher-order assembly at near-atomic resolutions by subtomogram averaging. The structures surprisingly reveal that the authentic intrinsically disordered linker protein CsoS2 interacts with Rubiscos in native carboxysomes but functions distinctively in the two α-carboxysomes. In contrast to the uniform Rubisco-CsoS2 association in the
Cyanobium
α-carboxysome, CsoS2 binds only to the Rubiscos close to the shell in the
Halo
α-carboxysome. Our findings provide critical knowledge of the assembly principles of α-carboxysomes, which may aid in the rational design and repurposing of carboxysome structures for new functions.
To address the issue of dynamic 3D circular features recognition in robot arm grasping, we propose a feature-based and incremental simultaneous points and circles structure from motion system. First, ...we represent the 3D target scene with sparse point cloud from multiple observations. The fundamental points construction pipeline combines the benefits of feature-based mapping and probabilistic depth estimation, which reduce the computational cost of generating practical 3D structures. Second, accurate 3D circles are extracted from the keyframes and are optimized in the backend. The circles construction pipeline attempts to find potential circles in the produced sparse point cloud and apply an adjusted level set method to do a novel 3D circle optimization process, which can work on keyframes smoothly. The integrated system is compared with other real-time construction systems and outperforms in industry scenes with more stable land-marks. Meanwhile the experimental results illustrate the ability of capturing circular features in target scenes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A series of triarylimidazoles was synthesized and characterized electrochemically. The synthetic route is general, providing a pathway to 30 redox mediators that exhibit a > 700 mV range of ...accessible potentials. Most of the triarylimidazoles display three oxidation peaks where the first redox couple is quasi-reversible. The electronic character of the substituents affects the oxidation potential. This is exemplified by a linear correlation between the first oxidation potential and the sum of the Hammett σ+ substituent constants, as well as with a series of calculated ionization potentials. We close by putting forward a rule of thumb stating that for a given mediator, the upper limit of accessible potentials can be extended by at least 500 mV beyond the largest recorded value. A rationale, the conditions under which the rule is likely to apply, and an example are provided.
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Orbital angular momentum (OAM) has made it possible to regulate classical waves in novel ways, which is more energy- or information-efficient than conventional plane wave technology. This work aims ...to realize the transition of antenna radiation mode through the rapid design of an anisotropic dielectric lens. The deep learning neural network (DNN) is used to train the electromagnetic properties of dielectric cell structures. Nine variable parameters for changing the dielectric unit structure are present in the input layer of the DNN network. The trained network can predict the transmission phase of the unit cell structure with greater than 98% accuracy within a specific range. Then, to build the corresponding relationship between the phase and the parameters, the gray wolf optimization algorithm is applied. In less than 0.3 s, the trained network can predict the transmission coefficients of the 31 × 31 unit structure in the arrays with great accuracy. Finally, we provide two examples of neural network-based rapid anisotropic dielectric lens design. Dielectric lenses produce the OAM modes +1, -1, and -1, +2 under TE and TM wave irradiation, respectively. This approach resolves the difficult phase matching and time-consuming design issues associated with producing a dielectric lens.
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