Background
NASH is one of the fastest growing liver diseases that leads to severe steatosis, inflammation and ultimately liver injury. However, the pathophysiological mechanisms of NASH remain ...unclear and pharmacological treatment against the disease is unavailable currently. Ferroptosis is a non‐apoptotic form of cell death induced by iron‐dependent lipid peroxidation. Since NASH progression is accompanied by massive lipid accumulation, which generates lipotoxic species, we investigated the role of ferroptosis in NASH progression.
Method
Mice were fed on MCD‐diet to mimic NASH progression and gene expression in liver was analysed by RNA‐seq. The occurrence of hepatic ferroptosis was measured by lipid ROS level, electron microscopy and in vivo PI staining. The beneficial effects of ferroptosis inhibitors on NASH was evaluated by liver pathology analysis. The mechanism of lipid ROS induced lipid droplets accumulation was investigated by in vitro cell culture.
Results
RNA‐seq analysis suggested that elevated arachidonic acid metabolism promotes ferroptosis in MCD‐diet fed mouse livers, which was further demonstrated by lipid ROS accumulation, morphological change of mitochondria and increased cell death. Iron accumulation was detected in the liver and the serum of MCD‐fed mice. Scavenging of ferroptosis‐linked lipid peroxides reduced lipid accumulation both in vivo and in vitro. Importantly, ferroptosis inhibitors alleviated MCD‐diet induced inflammation, fibrogenesis and liver injury. Finally, lipid ROS promotes liver steatosis by boosting lipid droplets formation.
Conclusion
Our results demonstrate an important role of ferroptosis in the progression of MCD‐diet induced NASH and suggest that ferroptosis may serve as a therapeutic target for NASH treatment.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Aim
Platinum‐based chemotherapy is the standard treatment for ovarian cancer. However, tumor cells' resistance to platinum drugs often occurs. This paper provides a review of Forkhead box O (FOXO) ...protein's role in platinum resistance of ovarian cancer which hopefully may provide some further guidance for the treatment of platinum‐resistant ovarian cancer.
Methods
We reviewed a 128 published papers from authoritative and professional journals on FOXO and platinum‐resistant ovarian cancer, and adopts qualitative analyses and interpretation based on the literature.
Results
Ovarian cancer often has abnormal activation of cellular pathways, the most important of which is the PI3K/AKT pathway. FOXOs act as crucial downstream factor of the PI3K/Akt pathway and are negatively regulated by it. DNA damage response and apoptosis including the relationship between FOXOs and ATM‐Chk2‐p53 are essential for platinum resistance of ovarian cancer. Through gene expression analysis in platinum‐resistant ovarian cancer cell model, it was found that FoxO‐1 is decreased in platinum‐resistant ovarian cancer, so studying the role of FOXO in the pathway on platinum‐induced apoptosis may further guide the treatment of platinum‐resistant ovarian cancer.
Conclusions
There are many drug resistance mechanisms in ovarian cancer, wherein the decrease in cancer cells apoptosis is one of the important causes. Constituted by a series of transcription factors evolving conservatively and mainly working in inhibiting cancer, FOXO proteins play various roles in cells' antitumor response. More and more evidence suggests that we need to re‐understand the role that FOXOs have played in cancer development and treatment.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Rhodiola rosea L., a worldwide botanical adaptogen, has been confirmed to possess protective effects of inflammatory injury for many diseases, including cardiovascular diseases, neurodegenerative ...diseases, diabetes, sepsis, and cancer. This paper is to review the recent clinical and experimental researches about the anti-inflammatory effects and the related mechanisms of Rhodiola rosea L. extracts, preparations, and the active compounds. From the collected information reviewed, this paper will provide the theoretical basis for its clinical application, and provide the evidences or guidance for future studies and medicinal exploitations of Rhodiola rosea L.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Five new Keggin-based compounds, namely CuI(dm4bt)24GeW12O40 (1), M4II(dm4bt)8(GeW12O40)2(H2O)2·4H2O (M = Ni for 2 and Co for 3), Co4II(dm4bt)8(SiW12O40)2(H2O)2·6H2O (4) and ...Cu2II(H2bdpm)(HBW12O40)(H2O)2·H2O (5) (dm4bt = 2,2′-dimethyl-4,4′-bithiazole, H2bdpm = 1,1′-bis(3,5-dimethyl-1H-pyrazolate)methane), were synthesized through traditional hydrothermal methods. Compounds 1–5 can be used as photoelectric multifunctional sensors to detect various ions. As electrochemical sensors, n-CPEs have a good sensitivity and wide concentration range for nitrite. As fluorescent sensors, the title compounds have remarkable fluorescence detection performance for Cr2O72−. Furthermore, we modified the compounds as catalysts to investigate their catalytic activities for CO2 reduced to CO and the reduction of Cr(vi) to Cr(iii). The results show that these compounds have high catalytic activities.
Developing heterogeneous photocatalysts for the applications in harsh conditions is of high importance but challenging. Herein, by converting the imine linkages into quinoline groups of ...triphenylamine incorporated covalent organic frameworks (COFs), two photosensitive COFs, namely TFPA-TAPT-COF-Q and TFPA-TPB-COF-Q, are successfully constructed. The obtained quinoline-linked COFs display improved stability and photocatalytic activity, making them suitable photocatalysts for photocatalytic reactions under harsh conditions, as verified by the recyclable photocatalytic reactions of organic acid involving oxidative decarboxylation and organic base involving benzylamine coupling. Under strong oxidative condition, the quinoline-linked COFs show a high efficiency up to 11831.6 μmol·g
·h
and a long-term recyclable usability for photocatalytic production of H
O
, while the pristine imine-linked COFs are less catalytically active and easily decomposed in these harsh conditions. The results demonstrate that enhancing the linkage robustness of photoactive COFs is a promising strategy to construct heterogeneous catalysts for photocatalytic reactions under harsh conditions.
Ferroptosis is a non-apoptotic form of cell death characterized by the iron-dependent lipid peroxidation and is implicated in several human pathologies, such as tissue ischemia, neurodegeneration, ...and cancer. Ferroptosis appears to be high cell-context dependent and the regulation of ferroptosis by physiological or pathological conditions are unclear. Here, we report that tumor-derived IDH1 mutation sensitizes cells to ferroptosis. Deletion of the mutant IDH1 allele in IDH1 heterozygous tumor cells or pharmacological inhibition of mutant IDH1 to produce the oncometabolite D-2-hydroxyglutarate (D-2-HG) confers resistance to erastin-induced ferroptosis. Conversely, ectopic expression of mutant IDH1 or treatment of cells with cell-permeable D-2-HG promotes the accumulation of lipid reactive oxygen species (ROS) and subsequently ferroptosis. Mechanistically, mutant IDH1 reduces the protein level of the glutathione peroxidase 4 (GPX4), a key enzyme in removing lipid ROS and ferroptosis, and promotes depletion of glutathione. Our results uncover a new role of mutant IDH1 and 2-HG in ferroptosis.
Laser additive manufacturing (LAM) is applied to manufacture particles reinforced composites due to its high designability, non-mold and high working flexibility. In this paper, TiC particles ...reinforced Inconel 625 composites were fabricated by LAM technology. Microstructure and chemical compositions of the composites were detected using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). Meanwhile, macroscopic Brinell and micro Vickers hardness and in situ tensile test were applied to explore the hardness and fracture behavior of the composites. Results indicate that the microstructure of the composites consist of randomly distributed and partially melted TiC particle reinforcements, and in situ formed MC (M = Nb, Ti and Mo) precipitates with rod like shape appearing in interdendritic areas with a refined microstructure. A MC (M = Nb, Ti and Mo) transition region is observed at the interface between TiC/γ matrix. The hardness of composites was 231 Brinell, 56% higher than that of the laser additive manufactured Inconel 625. However, high hardness and brittleness of reinforcements and precipitates cause unwanted cracks generation during deformation of the materials, and which will later propagate into the matrix and lead to final failure of the composites. The transition region at TiC/γ matrix interface with coherent phase boundary enhanced the bonding strength thus no peeling of particles were observed during the fracture test.
Display omitted
•A TiC particle and precipitates reinforced Inconel625 composite is proposed.•MC carbides formed both at TiC/γ matrix interface and interdendritic areas.•Initial cracks generate inside TiC due to the coherent bonding at interface.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objective
The skin is the second most affected organ after articular involvement in systemic lupus erythematosus (SLE) patients. Cutaneous involvement occurs in approximately 80% of patients during ...the course of SLE. Interaction between the host and skin microorganism is a complex process. There are few studies on the diversity of skin microbes in SLE patients. Therefore, this study aims to explore the relationship between skin microorganisms and SLE.
Methods
A total of 20 SLE patients, 20 controls with rosacea and 20 healthy controls were selected as study subjects. Both the skin microbiota of rash region and non-rash region for each SLE patient were collected.16S rRNA gene sequencing was used to detected skin microbiota from 80 specimens. α-Diversity and β-diversity of skin microbiota were analyzed based on operational taxonomic units (OTUs) and minimal entropy decomposition (MED). Using Wilcoxon test and Linear Discriminate Analysis Effect Size (LEfSe), skin microbial diversity and composition were analyzed. Functional capabilities of microbiota were estimated through Kyoto Encyclopedia of Genes and Genomes database.
Results
Compared to rash region of SLE, diversity and richness were increased in healthy controls, and decreased in non-rash region of SLE and rash region of controls with rosacea. Additionally, changes of skin microbial composition were found at different taxonomic levels between four groups. For example, genus Halomonas was increased and genera Pelagibacterium, Novosphingobium, and Curvibacter were decreased in rash region compared to non-rash region of SLE based on OTUs and MED. Based on OTUs, metabolic pathways were also found differences in SLE patients, such as Xenobiotics Biodegradation and Metabolism.
Conclusion
Compositions and diversity of skin microbiota in SLE patients are changed. This pilot study provides some suggestive evidence for further exploration of skin microbiota in SLE patients with cutaneous involvement.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Ag nanorods receive intensive attention due to the excellent plasmonic properties. However, the difficulty in synthesis of monodisperse Ag nanorods with broad aspect ratios has limited their in‐depth ...applications. Here, a seed‐mediated method is reported for the synthesis of Ag nanorods with lengths from 65 to 5000 nm, corresponding to aspect ratios from 2 to 156. The plasmonic resonance is tuned from visible to mid‐infrared wavelength. The synthesis protocol relies on robust Au seeds synthesized in N,N‐dimethylformamide (DMF), which induces the one‐dimensional (1D) growth of Ag atoms. To maintain symmetry breaking initiated by the Au seeds, the reduction rate of Ag+ is decreased by adding hexadecyltrimethylammonium chloride (CTAC) to form AgCl particles. The optimized conditions to prevent the homogeneous nucleation of Ag nanoparticles and residue of AgCl particles in products are identified, under which the conversion efficiency of Ag ions to Ag nanorods is evaluated about 48%. More importantly, the anisotropic Ag nanorods are self‐assembled into monolayers at interfaces with the long axis of Ag nanorods perpendicular or parallel to the interfaces, respectively. The as‐fabricated monolayers exhibit uniform and reproducible surface‐enhanced Raman scattering (SERS) activities. The optimal SERS performance is achieved from Ag nanorod monolayer with vertical orientation and the longest rod length.
Ag nanorods synthesized through the seed‐mediated method exhibit extremely broad light response range covering from the visible to mid‐infrared parts of the spectrum by tuning the aspect ratios from 2 to ≈160. Self‐assembled Ag nanorod monolayers with controlled orientation are first realized at the interfaces and are readily transferred to arbitrary solid substrates for device‐based applications.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Exposed to crosswinds, dynamic response of the train and the guideway are the important aspects in the design of the high-speed maglev transit system. Firstly, the aerodynamic characteristics of a ...maglev vehicle were tested through a wind tunnel test. The proportional-integral-derivative-acceleration (PIDA) control algorithm, which combines a proportional-integral-derivative (PID) controller and acceleration feedback, was used to adjust the levitation and guidance control system of the maglev train. The spatial analysis model of the wind-static suspension-maglev train-guideway (WSMG) system and wind-moved maglev train-guideway (WMMG) were established. Subsequently, the influences of average wind, fluctuating wind, wind speeds, and vehicle speeds on the dynamic response of the maglev system were analyzed. The results indicate that the PIDA controller can eliminate the steady-state error of the magnetic gap caused by crosswinds. Compared with the PDA controller, the PIDA controller can reduce approximately 40% of the lateral displacement of the vehicle body. The average wind only changes the equilibrium position of the train, and the fluctuating winds and track irregularities are the significant cause for the vibration of the maglev train-guideway system. The lateral vibration of the vehicle is more sensitive to the wind velocity. The high-speed maglev train should stop running when the wind speed exceeds 30 m/s.
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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
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