Yingxiongling shale is characterized by high-frequency cyclic deposition, and the rocks in the area are classified into five rock types, which means that this area has complex geological features. ...Different types of rocks have nonhomogeneity and unclear stress sensitivity characteristics, which are important for reservoir stimulation and production. In this paper, the permeability stress sensitivity characteristics of different types of rocks are evaluated based on the elastic parameter stress sensitivity results, and the stress sensitivity parameters of rocks in the in situ stress state are proposed. The reservoir engineering quality of different types of rocks is evaluated by combining their microscopic pore characteristics with stress sensitivity characteristics. The results show that the stress sensitivity characteristics of different types of rocks are affected by the number of laminae and clay mineral content, the elastic parameter stress sensitivity of laminated rocks is stronger than that of layered rocks, and that of argillaceous rocks is stronger than that of limy rocks in layered shale. The permeability stress sensitivity of layered rocks is stronger than that of laminated rocks, that of argillaceous rocks is stronger than that of limy rocks in layered shale, and that of sandstone is the strongest. The laminated rocks are more capable of forming cracks and have better pore connectivity than the layered rocks. Finally, based on the elastic parameter stress sensitivity coefficient, a new coefficient is proposed to improve the permeability stress sensitivity, and the improved permeability stress sensitivity coefficient is used to evaluate the permeability characteristics of the reservoir under the in situ stress. Then, the quality of the main reservoirs was evaluated by the new parameters; the reservoir quality of laminated limy shale was the best and that of layered argillaceous shale was the worst. This study provides theoretical support for the target layer preference of Yingxiongling shale and highly efficient development.
Intrahepatic cholangiocarcinoma (ICC) is highly invasive and carries high mortality due to limited therapeutic strategies. In other solid tumors, immune checkpoint inhibitors (ICIs) target cytotoxic ...T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD1), and the PD1 ligand PD-L1 has revolutionized treatment and improved outcomes. However, the relationship and clinical significance of CTLA-4 and PD-L1 expression in ICC remains to be addressed. Deciphering CTLA-4 and PD-L1 interactions in ICC enable targeted therapy for this disease. In this study, immunohistochemistry (IHC) was used to detect and quantify CTLA-4, forkhead box protein P3 (FOXP3), and PD-L1 in samples from 290 patients with ICC. The prognostic capabilities of CTLA-4, FOXP3, and PD-L1 expression in ICC were investigated with the Kaplan-Meier method. Independent risk factors related to ICC survival and recurrence were assessed by the Cox proportional hazards models. Here, we identified that CTLA-4
lymphocyte density was elevated in ICC tumors compared with peritumoral hepatic tissues (
<.001), and patients with a high density of CTLA-4
tumor-infiltrating lymphocytes (TILs
) showed a reduced overall survival (OS) rate and increased cumulative recurrence rate compared with patients with TILs
(
<.001 and
= .024, respectively). Similarly, patients with high FOXP3
TILs (TILs
) had poorer prognoses than patients with low FOXP3
TILs (
= .021,
= .034, respectively), and the density of CTLA-4
TILs was positively correlated with FOXP3
TILs (Pearson
= .31,
<.001). Furthermore, patients with high PD-L1 expression in tumors (Tumor
) and/or TILs
presented worse OS and a higher recurrence rate than patients with TILs
Tumor
. Moreover, multiple tumors, lymph node metastasis, and high Tumor
/TILs
were independent risk factors of cumulative recurrence and OS for patients after ICC tumor resection. Furthermore, among ICC patients, those with hepatolithiasis had a higher expression of CTLA-4 and worse OS compared with patients with HBV infection or undefined risk factors
= .018). In conclusion, CTLA-4 is increased in TILs in ICC and has an expression profile distinct from PD1/PD-L1. Tumor
/TILs
is a predictive factor of OS and ICC recurrence, suggesting that combined therapy targeting PD1/PD-L1 and CTLA-4 may be useful in treating patients with ICC.
Magnetite nanoparticles were prepared by coprecipitation of Fe
2+ and Fe
3+ with NH
4OH, and then, amino silane was coated onto the surface of the magnetite nanoparticles. Transmission electronic ...microscopy shows the average size of 7.5 nm in diameter. Powder X-ray diffraction and electronic diffraction measurements show the spinel structure for the magnetite nanoparticles. FT–IR spectra indicate that amino silane molecules have been bound onto the surface of the magnetite nanoparticles by FeOSi chemical bonds. Energy dispersive X-ray spectroscopy (SEM–EDS) indicates atomic ratio of 96.75:3.25 for Fe:Si, implying a nearly monolayer coating of amino silane on the magnetite particle surface according to a rough calculation. By an enzyme-linked assay, it was proved that the amino silane-coated magnetite nanoparticles could significantly improve the protein immobilization.
Severe inflammatory reactions caused by macrophage activation can trigger a systemic immune response. In the present study, we observed the anti-inflammatory properties of hispidin on LPS induced ...RAW264.7 macrophage cells. Our results showed that hispidin treatment significantly reduced the production of cellular NO, IL-6 and reactive oxygen species (ROS) while has not inhibitory effect on TNF-α productions. Excitingly, hispidin treatment retains the phagocytosis ability of macrophages which enabling them to perform the function of removing foreign invaders. Signaling studies showed, hispidin treatment dramatic suppressed the LPS induced mitogen activated protein kinases (MAPK) and JAK/STAT activations. In conclusion, our findings suggest that hispidin may be a new therapeutic target for clinical treatment of macrophages-mediated inflammatory responses.
Heterointerfaces between complex oxides have sparked considerable interest due to their fascinating physical properties and their offering of new possibilities for next-generation electronic devices. ...The key to realize practical applications is the control through external stimuli. In this study, we take the self-assembled BiFeO3–CoFe2O4 tubular interface as a model system to demonstrate the nonvolatile electric control of the local conduction at the complex oxide tubular interface. The fundamental mechanism behind this modulation was explored based on static and dynamic conductive atomic force microscopies. We found the movement of oxygen vacancies in the BiFeO3–CoFe2O4 heterostructure is the key to drive this intriguing behavior. This study delivers a possibility in developing next-generation electronic devices.
Renal artery stenosis (RAS) causes severe renovascular hypertension, worsening kidney function, and increased cardiovascular morbidity. According to recent studies, mesenchymal stem cells (MSCs) ...administration is a promising therapy for the improvement of RAS outcomes. The meta-analysis aims to evaluate the therapeutic effects of MSC therapy on RAS. We performed a search in MEDLINE, Web of Science, Embase, and Cochrane Library from inception to 5, October 2022. We included 16 preclinical and 3 clinical studies in this meta-analysis. In preclinical studies, the pooled results indicated that animals treated with MSCs had lower levels of systolic blood pressure (SBP) (SMD = - 1.019, 95% CI - 1.434 to - 0.604, I
= 37.2%, P = 0.000), serum creatinine (Scr) (SMD = - 1.112, 95% CI - 1.932 to - 0.293, I
= 72.0%, P = 0.008), and plasma renin activity (PRA) (SMD = - 0.477, 95% CI - 0.913 to 0.042, I
= 43.4%, P = 0.032). The studies also revealed increased levels of renal blood flow (RBF) in stenotic kidney (STK) (SMD = 0.774, 95% CI - 0.351 to 1.197, I
= 0%, P = 0.000) and the glomerular filtration rate (GFR) of STK (SMD = 1.825, 95% CI 0.963 to 2.688, I
= 72.6%, P = 0.000). In clinical studies, the cortical perfusion and fractional hypoxia of the contralateral kidney (CLK) were alleviated by MSC therapy. Taken together, this meta-analysis revealed that MSCs therapy might be a promising treatment for RAS. However, due to the discrepancy between preclinical studies and early clinical trials outcomes, MSC therapy couldn't be recommended in clinical care for the moment, more high-quality randomized controlled clinical trials are needed to validate our conclusions and standardize MSCs protocols.
The thyroid hormone (TH)-controlled recruitment process of brown adipose tissue (BAT) is not fully understood. Here, we show that long-term treatment of T3, the active form of TH, increases the ...recruitment of thermogenic capacity in interscapular BAT of male mice through hyperplasia by promoting the TH receptor α-mediated adipocyte progenitor cell proliferation. Our single-cell analysis reveals the heterogeneous nature and hierarchical trajectory within adipocyte progenitor cells of interscapular BAT. Further analyses suggest that T3 facilitates cell state transition from a more stem-like state towards a more committed adipogenic state and promotes cell cycle progression towards a mitotic state in adipocyte progenitor cells, through mechanisms involving the action of Myc on glycolysis. Our findings elucidate the mechanisms underlying the TH action in adipocyte progenitors residing in BAT and provide a framework for better understanding of the TH effects on hyperplastic growth and adaptive thermogenesis in BAT depot at a single-cell level.
Cryptotanshinone (CT), isolated from the plant
, has been reported to have potential anticancer effects on human prostate and breast cancer cells. However, the mechanisms of action of CT on gastric ...cancer (GC) cells are not well understood. Here we investigated the antitumor effects of CT on GC cells and its possible molecular mechanism. We found CT suppressed viability of twelve GC cell lines in a dose-dependent manner. CT induced cell cycle arrest at the G2/M phase and mitochondrial apoptosis accompanying the accumulation of reactive oxygen species (ROS). Pretreatment with ROS inhibitor N-acetyl-L-cysteine (NAC) blocked CT-induced apoptosis. CT increased p-JNK and p-p38, and decreased p-ERK and p-STAT3 protein expression, these effects were prevented by NAC. Furthermore, a xenograft assay showed that CT significantly inhibited MKN-45 cell-induced tumor growth
by increasing expression of pro-apoptotic proteins (p-JNK, p-38 and cleaved-caspase-3) and reducing expression of anti-apoptotic proteins (p-ERK and p-STAT3) without adverse effects on nude mice weight. In conclusion, CT induced apoptosis and cell cycle arrest in GC cells via ROS-mediated MAPK and AKT signaling pathways, and this CT may be a useful compound for the developing anticancer agents for GC.
Iodine is an essential micronutrient for producing thyroid hormone (TH); however, iodide excess can lead to adverse thyroidal effects. Unfortunately, the lack of a proper in vitro model system ...hampered the studies of the effect of iodide excess on thyroid physiology and pathology. Here, we demonstrated that excessive iodide intake downregulated the genes related to TH synthesis in the thyroids of mice. Since sodium iodide has no effect on these genes in cultured cell lines, we developed a three-dimensional (3D) culture system to enable the murine thyrocytes to form organoids in vitro with thyroid follicle-like structures and function and found that the in vivo effect of iodide excess could be mimicked in these thyroid organoids. Our data indicate that iodide excess mainly activated the XBP1-mediated unfolded protein response in both murine thyroid and thyroid organoids, while activation of XBP1 was able to mimic the sodium iodide effect on genes for the synthesis of TH in murine thyroid organoids. Lastly, our results suggest that XBP1 might transcriptionally repress the genes involved in the synthesis of TH. Based on these findings, we propose that iodide excess inhibits the transcription of genes related to TH synthesis through a mechanism involving XBP1-mediated action.
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