Tumor microenvironment and metabolic reprogramming are critical for tumor metastasis. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are widely involved in the formation of tumor ...microenvironment and present oncogenic phenotypes to facilitate lymph node metastasis (LNM) in response to small extracellular vesicles (sEV) released by gastric cancer (GC) cells. However, whether metabolic reprograming mediates transformation of BM-MSCs remains elusive. Herein, we revealed that the capacity of LNM-GC-sEV educating BM-MSCs was positively correlated with the LNM capacity of GC cells themselves. Fatty acid oxidation (FAO) metabolic reprogramming was indispensable for this process. Mechanistically, CD44 was identified as a critical cargo for LNM-GC-sEV enhancing FAO via ERK/PPARγ/CPT1A signaling. ATP was shown to activate STAT3 and NF-κB signaling to induce IL-8 and STC1 secretion by BM-MSCs, thereby in turn facilitating GC cells metastasis and increasing CD44 levels in GC cells and sEV to form a persistent positive feedback loop between GC cells and BM-MSCs. The critical molecules were abnormally expressed in GC tissues, sera and stroma, and correlated with the prognosis and LNM of GC patients. Together, our findings uncover the role of metabolic reprogramming mediated BM-MSCs education by LNM-GC-sEV, which presents a novel insight into the mechanism underlying LNM and provides candidate targets for GC detection and therapy.
Abstract
Hierarchical domain structures associated with oxygen octahedra tilting patterns were observed in lead-free (Bi
1/2
Na
1/2
)TiO
3
ceramics using aberration-corrected high-resolution ...transmission electron microscopy (HRTEM). Three types of domains are induced by distinct mechanisms: the ‘orientation-domain’ is induced at micrometer scale formed by different tilting orientations of the oxygen octahedra, the ‘meso-chemical-domain’ occurs at a few tens of nanometer scale by chemical composition variation on the A-site in the ABO
3
perovskite structure, and the ‘nano-cluster-region’ runs across several unit-cells with apparent A-site cation segregation with oxygen vacancies clustering around Na cations. Based on HRTEM amplitude contrast imaging (ACI), the correlation between the oxygen octahedral tilting pattern and compositional non-stoichiometry was established. The role of the hierarchical domain structure associated with the tilting patterns of the oxygen octahedra on the ferroelectric behavior of (Bi
1/2
Na
1/2
)TiO
3
is also discussed.
The aim of this study was to analyze the findings of MDCT performed after direct lymphangiography in patients with diffuse pulmonary lymphangiomatosis.
Twenty-three patients (13 male and 10 female ...patients) diagnosed with diffuse pulmonary lymphangiomatosis on the basis of clinical features and findings from imaging, bronchoscopy, and pathologic analysis were retrospectively evaluated. All patients underwent pulmonary MDCT after direct lymphangiography, surgical operation or open lung biopsy, and histopathologic examination. MDCT images were analyzed by two experienced radiologists independently.
MDCT after direct lymphangiography revealed numerous intrathoracic abnormalities, including abnormal distribution of contrast medium, dilatation of lymphatic channels, mediastinal soft-tissue infiltration, and peribronchovascular thickening. Nineteen patients had interlobular septal thickening, 18 had diffuse ground-glass opacities, 22 had pleural effusion, 14 had extrapleural soft-tissue thickening, 20 had pericardial effusion and thickened pericardium, 10 had multiple lymphadenopathy in mediastinum, and five had mediastinal, pericardial, and thoracic aeroceles.
MDCT performed after direct lymphangiography is well suited to clarify the characteristics of intrathoracic disorders and is an excellent tool in the diagnosis of diffuse pulmonary lymphangiomatosis.
A 53‐year‐old man undergoing painless colonoscopy for long‐term diarrhea. After colonoscopy withdrawing to the sigmoid colon, a local perforation was found, about 3 cm in size, oval in shape. We used ...a two‐channel endoscope and grip to pull the edges of the intestinal wall on both sides of the perforation site to close together, and then repair the 3 cm oval perforation of the colon through multiple ordinary titanium clips. The patient had no obvious infection after surgery and recovered well after 1 month of follow‐up. Preliminary experience has shown that using multiple titanium clips under dual‐channel endoscope to zipper suture can effectively repair 3 cm iatrogenic colonic perforations.
•A frequency-domain algorithm for very fast transient over-voltage (VFTO) and its conducted disturbance via voltage transformer (VT) is proposed, which calculates the whole process in frequency ...domain with VFTO frequency spectrum and the VT transfer function for gas-insulated switchgear (GIS) substations.•The proposed algorithm has been applied in the simulation of VFTO and its disturbance in the 1000 kV Wuhu substation, of which the calculated and measured VFTO waveforms are in good agreement for verification.•The transfer functions of the two types 1000 kV GIS VT are obtained by the impulse test method, and the conducted disturbances are also calculated with their severity and suppression method analyzed.
Simulation of very fast transient over-voltage (VFTO) and its conducted disturbance via voltage transformer (VT) is significant in guiding the insulation design and electromagnetic compatibility of gas-insulated switchgear (GIS) substations. However, the commonly used time-domain algorithms are difficult to deal with the complex frequency-dependent parameters in the VFTO simulation, and might introduce instability of conducted disturbance due to an active circuit synthesis of the VT in some cases. In this paper, a frequency-domain algorithm is proposed, which calculates the VFTO in the frequency domain and then directly uses the VFTO frequency spectrum and the VT transfer function to calculate the conducted disturbance without circuit synthesis. The proposed algorithm has been applied in the simulation of VFTO and its disturbance in the 1000 kV Wuhu substation. The calculated and measured VFTO waveforms are in good agreement, verifying the accuracy of the algorithm. The transfer functions of the 1000 kV GIS VT are obtained by the impulse test method, and the conducted disturbances are also calculated with their severity and suppression method analyzed. The proposed frequency-domain algorithm covers the whole calculation process from VFTO to its conducted disturbance and has good engineering application potential in the simulation, with better convenience and stability.
This study investigates the activity of tropical cyclones (TCs) in the Bay of Bengal (BOB) from 1979 to 2018 to discover the mechanism affecting the contribution rate to the meridional moisture ...budget anomaly (MMBA) over the southern boundary of the Tibetan Plateau (SBTP). May and October–December are the bimodal phases of BOB TC frequency, which decreases month by month from October to December and is relatively low in May. However, the contribution rate to the MMBA is the highest in May. The seasonal variation in the meridional position of the westerlies is the key factor affecting the contribution rate. The relatively southern (northern) position of the westerlies in November and December (May) results in a lower (higher) contribution rate to the MMBA. This mechanism is confirmed by the momentum equation. When water vapor enters the westerlies near the trough line, the resultant meridional acceleration is directed north. It follows that the farther north the trough is, and the farther north the water vapor can be transported. When water vapor enters the westerlies from the area near the ridge line, for Type-T (Type-R) TCs, water vapor enters the westerlies downstream of the trough (ridge). Consequently, the direction of the resultant meridional acceleration is directed south and the resultant zonal acceleration is directed east (west), which is not conducive to the northward transport of water vapor. This is especially the case if the trough or ridge is relatively south, as the water vapor may not cross the SBTP.
To effectively protect the host from viral infection while avoiding excessive immunopathology, the innate immune response must be tightly controlled. However, the precise regulation of antiviral ...innate immunity and the underlying mechanisms remain unclear. Here, we find that sirtuin3 (SIRT3) interacts with mitochondrial antiviral signaling protein (MAVS) to catalyze MAVS deacetylation at lysine residue 7 (K7), which promotes MAVS aggregation, as well as TANK-binding kinase I and IRF3 phosphorylation, resulting in increased MAVS activation and enhanced type I interferon signaling. Consistent with these findings, loss of
in mice and zebrafish renders them more susceptible to viral infection compared to their wild-type (WT) siblings. However,
and
double-deficient mice exhibit the same viral susceptibility as their WT littermates, suggesting that loss of
in
-deficient mice may counteract the increased viral susceptibility displayed in
-deficient mice. Thus, we not only demonstrate that SIRT3 positively regulates antiviral immunity in vitro and in vivo, likely via MAVS, but also uncover a previously unrecognized mechanism by which SIRT3 acts as an accelerator and SIRT5 as a brake to orchestrate antiviral innate immunity.
The huge increase in the communication network rate has made the application fields and scenarios for vehicular ad hoc networks more abundant and diversified and proposed more requirements for the ...efficiency and quality of data transmission. To improve the limited communication distance and poor communication quality of the Internet of Vehicles (IoV), an optimal intelligent routing algorithm is proposed in this paper. Combined multi-weight decision algorithm with the greedy perimeter stateless routing protocol, designed and evaluated standardized function for link stability. Linear additive weighting is used to optimize link stability and distance to improve the packet delivery rate of the IoV. The blockchain system is used as the storage structure for relay data, and the smart contract incentive algorithm based on machine learning is used to encourage relay vehicles to provide more communication bandwidth for data packet transmission. The proposed scheme is simulated and analyzed under different scenarios and different parameters. The experimental results demonstrate that the proposed scheme can effectively reduce the packet loss rate and improve system performance.
In nature, certain animals share a common living environment with humans, thus these animals have become biomonitors of health effects related to various environmental exposures. As one of the most ...toxic environmental chemicals, lead (Pb) can cause detriment health effects to animals, plants, and even humans through different exposure pathways such as atmosphere, soil, food, water, and dust, etc. Sentinel animals played an “indicative” role in the researches of environmental pollution monitoring and human health. In order to comprehend the usage of sentinel animals in the indication of environmental Pb pollution and human Pb exposure completely, a combination of traditional review and visualization analysis based on CiteSpace literature was used to review earlier researches in this study. In the first instance, present researches on exposure sources and exposure pathways of Pb were summarized briefly, and then the studies using sentinel animals to monitor environmental heavy metal pollution and human health were combed. Finally, visualization software CiteSpace 5.8.R3 was used to explore and analyze the hotspots and frontiers of lead exposure and sentinel animals researches at home and abroad. The results showed that certain mammals were good indicators for human lead exposure. Sentinel animals had been widely used to monitor the ecological environment and human lead exposure. Among them, the blood lead levels of small mammals, particularly for domestic dogs and cats, had a significant correlation with the blood lead levels of human living in the same environment. It indicated that certain biological indicators in animals can be used as surrogates to monitor human body exposure to heavy metals. This study also explored the challenges and perspectives that may be faced in sentinel animal research, in order to provide a certain theoretical basis and train of thought guidance for future research.
Effective therapies for stroke are still limited due to its complex pathological manifestations. QiShenYiQi (QSYQ), a component-based Chinese medicine capable of reducing organ injury caused by ...ischemia/reperfusion, may offer an alternative option for stroke treatment and post-stroke recovery. Recently, we reported a beneficial effect of QSYQ for acute stroke
modulation of the neuroinflammatory response. However, if QSYQ plays a role in subacute stroke remains unknown. The pharmacological action of QSYQ was investigated in experimental stroke rats which underwent 90 min ischemia and 8 days reperfusion in this study. Neurological and locomotive deficits, cerebral infarction, brain edema, and BBB integrity were assessed. TMT-based quantitative proteomics were performed to identify differentially expressed proteins following QSYQ treatment. Immunohistochemistry, western blot analysis, RT-qPCR, and ELISA were used to validate the proteomics data and to reveal the action mechanisms. Therapeutically, treatment with QSYQ (600 mg/kg) for 7 days significantly improved neurological recovery, attenuated infarct volume and brain edema, and alleviated BBB breakdown in the stroke rats. Bioinformatics analysis indicated that protein galectin-3 and its mediated inflammatory response was closely related to the beneficial effect of QSYQ. Specially, QSYQ (600 mg/kg) markedly downregulated the mRNA and protein expression levels of galectin-3, TNF-α, and IL-6 in CI/RI brain as well as serum levels of TNF-α and IL-6. Overall, our findings showed that the effective action of QSYQ against the subacute phase of CI/RI occurs partly
regulating galectin-3 mediated inflammatory reaction.
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