The microparticle-enhanced cultivation (MPEC) was used to enhance the production of Antrodin C by submerged fermentation of medicinal mushroom Antrodia cinnamomea. The crucial factors such as types, ...sizes, concentrations, and addition time of microparticles were optimized. The mechanism of MPEC on the membrane permeability and fluidity of A. cinnamomea and the expression of key genes in Antrodin C were investigated. When talc (18 μm, 2 g/L) was added into the fermentation liquid at 0 h, the promoting effect on Antrodin C was the best. The maximum yield of Antrodin C was 1615.7 mg/L, which was about 2.98 times of the control (541.7 mg/L). Talc slightly damaged the mycelia of A. cinnamomea, increased the release of intracellular constituents, and enhanced the index of unsaturated fatty acid. In addition, the key genes (IDI, E2.3.3.10, HMGCR, atoB) that might play an important role in the synthesis of the triquine-type sesquiterpene Antrodin C, were upregulated. In conclusion, talc increased the permeability and fluidity of cell membrane, upregulated the key genes and improved the biosynthesis process to enhance the yield of Antrodin C in the submerged fermentation of A. cinnamomea.
•Microparticles increased the production of Antrodin C of Antrodia cinnamomea.•The permeability and fluidity of cell membrane of A. cinnamomea were affected.•The morphology of the mycelia were changed by the microparticles.•The key genes in the biosynthesis of Antrodin C were upregulated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abdominal aortic aneurysm (AAA) is a serious vascular disease which is associated with vascular remodeling. CD38 is a main NAD
-consuming enzyme in mammals, and our previous results showed that CD38 ...plays the important roles in many cardiovascular diseases. However, the role of CD38 in AAA has not been explored. Here, we report that smooth-muscle-cell-specific deletion of CD38 (CD38
) significantly reduced the morbidity of AngII-induced AAA in CD38
Apoe
mice, which was accompanied with a increases in the aortic diameter, medial thickness, collagen deposition, and elastin degradation of aortas. In addition, CD38
significantly suppressed the AngII-induced decreases in α-SMA, SM22α, and MYH11 expression; the increase in Vimentin expression in VSMCs; and the increase in VCAM-1 expression in smooth muscle cells and macrophage infiltration. Furthermore, we demonstrated that the role of CD38
in attenuating AAA was associated with the activation of sirtuin signaling pathways. Therefore, we concluded that CD38 plays a pivotal role in AngII-induced AAA through promoting vascular remodeling, suggesting that CD38 may serve as a potential therapeutic target for the prevention of AAA.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Nonadiabatic dynamics simulation has become a powerful tool to describe nonadiabatic effects involved in photophysical processes and photochemical reactions. In the past decade, our group has ...developed generalized trajectory-based ab initio surface-hopping (GTSH) dynamics simulation methods, which can be used to describe a series of nonadiabatic processes, such as internal conversion, intersystem crossing, excitation energy transfer and charge transfer of molecular systems, and photoinduced nonadiabatic carrier dynamics of extended systems with and without spin–orbit couplings. In this contribution, we will first give a brief introduction to our recently developed methods and related numerical implementations at different computational levels. Later, we will present some of our latest applications in realistic systems, which cover organic molecules, biological proteins, organometallic compounds, periodic organic and inorganic materials, etc. Final discussion is given to challenges and outlooks of ab initio nonadiabatic dynamics simulations.
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IJS, KILJ, NUK, PNG, UL, UM
Electrocatalytic reduction of NO to NH3 (NORR) emerges as a promising route for achieving harmful NO treatment and sustainable NH3 generation. In this work, we first report that Mo2C is an active and ...selective NORR catalyst. The developed Mo2C nanosheets deliver a high NH3 yield rate of 122.7 μmol h–1 cm–2 with an NH3 Faradaic efficiency of 86.3% at −0.4 V. Theoretical computations unveil that the surface-terminated Mo atoms on Mo2C can effectively activate NO, promote protonation energetics, and suppress proton adsorption, resulting in high NORR activity and selectivity of Mo2C.
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IJS, KILJ, NUK, PNG, UL, UM
Main-group metal elements show great potential for exploring high-performance catalysts for electrochemical reduction of NO to NH3 (NORR) but remain largely unexplored. Herein, as a proof-of-concept, ...main-group In single atoms confined in an amorphous MoO3 substrate (In1/a-MoO3) are explored as an efficient NORR catalyst, showing a maximum NH3 yield of 242.6 μmol h−1 cm−2 and NH3-faradaic efficiency of 92.8%. Further experiments and theoretical results identify single-site In atoms as the dominating active centers to simultaneously inhibit the hydrogen evolution and optimize the hydrogenation energetics of the NO-to-NH3 pathway.
Over the past decades, climate change has exerted pronounced influences on the cryo-hydrologic environments in High Mountain Asia (HMA). Digital elevation models (DEMs) are one of the critical ...datasets required in many hydrology- and cryosphere-related studies in HMA, which include estimations of glacier mass balances and lake water storage changes and hydrological runoff modelling. Several global or near-global coverage DEMs (e.g. SRTM and ASTER missions) have been widely utilized for such studies. However, a comprehensive assessment of the quality of these DEMs, particularly over the high-relief HMA area, is still lacking. This study investigated the performances of seven public freely-accessed DEM datasets (ASTER GDEM V2, SRTM-3 V4.1 DEM, SRTM-1 DEM, AW3D30 DEM, VFP-DEM, MERIT DEM, Seamless SRTM-1 DEM) over the HMA region by referring to high-accuracy elevation data from ICESat altimetry. We also provided an additional detailed assessment for typical lake basins and extremely rugged areas in the Himalayas by using available global positioning system (GPS) measurements and gridded SETSM DEM raster data. Results show that AW3D30 exhibits the highest accuracy in HMA land areas among these datasets. The accuracy of all studied DEMs demonstrates high spatial variation, which shows the strongest relationship with slope among several topographical factors, such as elevation and aspect. Over these rugged terrains with a large slope, such as the Hengduan Mountains and Himalayas, the vertical accuracy is relatively low in all investigated DEMs. We established empirical models for fitting the relationship between DEM vertical error and mean slope, which can be used to estimate the average elevation errors for any given local or basin-scale DEM grids. In addition, this study identified regions with anomalous elevation data in each dataset caused by the imperfect void-filling processing scheme. In sum, the 3-arc-second MERIT DEM is judged to be relatively dependable for HMA which not only achieves good performances in statistical error values but also retains few void-filling anomalies. The 1-arc-second AW3D30 could be the most promising product over HMA with its high spatial resolution and accuracy, although some void-filling anomalies need to be noted in some regions.
•Seven global-scale freely available DEMs are collected for High Mountain Asia.•Vertical accuracies are assessed at three levels using multiple reference datasets.•AW3D30 exhibits the highest accuracy in HMA land areas among adopted datasets.•The statistical analyses and spatial distribution maps of vertical errors are provided.•The distributions of anomaly values of each datasets due to imperfect void-filling are investigated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•Cardiac and circulating levels of Metrnl were inhibited in streptozotocin (STZ)-induced mice and leptin receptor deficiency (db/db) mice.•Cardiac specific depletion of Metrnl ...worsened, while cardiomyocyte-specific OE of Metrnl reversed hyperglycemia-induced cardiac damage in mice.•Metrnl inactivated the cGAS/STING signaling pathway by activating the LKB1/AMPK/ULK1 signaling axis in DCM.
Meteorin-like hormone (Metrnl) is ubiquitously expressed in skeletal muscle, heart, and adipose with beneficial roles in obesity, insulin resistance, and inflammation. Metrnl is found to protect against cardiac hypertrophy and doxorubicin-induced cardiotoxicity. However, its role in diabetic cardiomyopathy (DCM) is undefined.
We aimed to elucidate the potential roles of Metrnl in DCM.
Gain- andloss-of-function experimentswere utilized to determine the roles of Metrnl in the pathological processes of DCM.
We found that plasma Metrnl levels, myocardial Metrnl protein and mRNA expressions were significantly downregulated in both streptozotocin (STZ)-induced (T1D) mice and leptin receptor deficiency (db/db) (T2D) mice. Cardiac-specific overexpression (OE) of Metrnl markedly ameliorated cardiac injury and dysfunction in both T1D and T2D mice. In sharp contrast, specific deletion of Metrnl in the heart had the opposite phenotypes. In parallel, Metrnl OE ameliorated, whereas Metrnl downregulation exacerbated high glucose (HG)-elicited hypertrophy, apoptosis and oxidative damage in primary neonatal rat cardiomyocytes. Antibody-induced blockade of Metrnl eliminated the effects of benefits of Metrnl in vitro and in vivo. Mechanistically, Metrnl activated the autophagy pathway and inhibited the cGAS/STING signaling in a LKB1/AMPK/ULK1-dependent mechanism in cardiomyocytes. Besides, Metrnl-induced ULK1 phosphorylation facilitated the dephosphorylation and mitochondrial translocation of STING where it interacted with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase that was responsible for ubiquitination and degradation of STING, rendering cardiomyocytes sensitive to autophagy activation.
Thus, Metrnl may be an attractive therapeutic target or regimen for treating DCM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
As the cellular power plant, mitochondria play a significant role in homeostasis. To maintain the proper quality and quantity of mitochondria requires both mitochondrial degradation and division. A ...selective type of autophagy, mitophagy, drives the degradation of excess or damaged mitochondria, whereas division is controlled by a specific fission complex; however, the relationship between these two processes, especially the role of mitochondrial fission during mitophagy, remains unclear. In this study, we report that mitochondrial fission is important for the progression of mitophagy. When mitophagy is induced, the fission complex is recruited to the degrading mitochondria through an interaction between Atg11 and Dnm1; interfering with this interaction severely blocks mitophagy. These data establish a paradigm for selective organelle degradation.
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•The Atg32-Atg11 interaction marks the degrading mitochondria•Mitochondrial fission is required for efficient mitochondrial degradation•The fission machinery is recruited to mitochondria by the Atg11 scaffold•The Atg11-Dnm1 interaction coordinates fission with mitophagy
Mitochondria division and degradation maintain proper organelle quality and quantity in the cell. Mao et al. provide insight into the coordination of mitochondrial fission and selective degradation by autophagy (mitophagy). Mitophagy progression requires mitochondrial fission. The scaffold Atg11 interacts with fission complex component Dnm1 and recruits fission machinery to mitochondria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Zebrafish exhibit a robust ability to regenerate their hearts following injury, and the immune system plays a key role in this process. We previously showed that delaying macrophage recruitment by ...clodronate liposome (-1d_CL, macrophage-delayed model) impairs neutrophil resolution and heart regeneration, even when the infiltrating macrophage number was restored within the first week post injury (Lai et al., 2017). It is thus intriguing to learn the regenerative macrophage property by comparing these late macrophages vs. control macrophages during cardiac repair. Here, we further investigate the mechanistic insights of heart regeneration by comparing the non-regenerative macrophage-delayed model with regenerative controls. Temporal RNAseq analyses revealed that -1d_CL treatment led to disrupted inflammatory resolution, reactive oxygen species homeostasis, and energy metabolism during cardiac repair. Comparative single-cell RNAseq profiling of inflammatory cells from regenerative vs. non-regenerative hearts further identified heterogeneous macrophages and neutrophils, showing alternative activation and cellular crosstalk leading to neutrophil retention and chronic inflammation. Among macrophages, two residential subpopulations (
Mac and
Mac 3) were enriched only in regenerative hearts and barely recovered after +1d_CL treatment. To deplete the resident macrophage without delaying the circulating macrophage recruitment, we established the resident macrophage-deficient model by administrating CL earlier at 8 d (-8d_CL) before cryoinjury. Strikingly, resident macrophage-deficient zebrafish still exhibited defects in revascularization, cardiomyocyte survival, debris clearance, and extracellular matrix remodeling/scar resolution without functional compensation from the circulating/monocyte-derived macrophages. Our results characterized the diverse function and interaction between inflammatory cells and identified unique resident macrophages prerequisite for zebrafish heart regeneration.
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