Promoting hematoma absorption is a novel therapeutic strategy for intracerebral hemorrhage (ICH); however, the mechanism of hematoma absorption is unclear. The present study explored the function and potential mechanism of CD36 in hematoma absorption using in vitro and in vivo ICH models. Hematoma absorption in CD36-deficient ICH patients was examined. Compared with patients with normal CD36 expression, CD36-deficient ICH patients had slower hematoma adsorption and aggravated neurologic deficits. CD36 expression in perihematomal tissues in wild-type mice following ICH was increased, whereas the hematoma absorption in CD36−/− mice was decreased. CD36−/− mice also showed aggravated neurologic deficits and increased TNF-α and IL-1β expression levels. The phagocytic capacity of CD36−/− microglia for RBCs was also decreased. Additionally, the CD36 expression in the perihematoma area after ICH in TLR4−/− and MyD88−/− mice was significantly increased, and hematoma absorption was significantly promoted, which was significantly inhibited by an anti-CD36 Ab. In vitro, TNF-α and IL-1β significantly inhibited the microglia expression of CD36 and reduced the microglia phagocytosis of RBCs. Finally, the TLR4 inhibitor TAK-242 upregulated CD36 expression in microglia, promoted hematoma absorption, increased catalase expression, and decreased the H2O2 content. These results suggested that CD36 mediated hematoma absorption after ICH, and TLR4 signaling inhibited CD36 expression to slow hematoma absorption. TLR4 inhibition could promote hematoma absorption and significantly improve neurologic deficits following ICH.
As a consequence of anthropogenic CO2-driven ocean acidification (OA), coastal waters are becoming increasingly challenging for calcifiers due to reductions in saturation states of calcium carbonate (CaCO3) minerals. The response of calcification rate is one of the most frequently investigated symptoms of OA. However, OA may also result in poor quality calcareous products through impaired calcification processes despite there being no observed change in calcification rate. The mineralogy and ultrastructure of the calcareous products under OA conditions may be altered, resulting in changes to the mechanical properties of calcified structures. Here, the warm water biofouling tubeworm, Hydroides elegans, was reared from larva to early juvenile stage at the aragonite saturation state (ΩA) for the current pCO2 level (ambient) and those predicted for the years 2050, 2100 and 2300. Composition, ultrastructure and mechanical strength of the calcareous tubes produced by those early juvenile tubeworms were examined using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and nanoindentation. Juvenile tubes were composed primarily of the highly soluble CaCO3 mineral form, aragonite. Tubes produced in seawater with aragonite saturation states near or below one had significantly higher proportions of the crystalline precursor, amorphous calcium carbonate (ACC) and the calcite/aragonite ratio dramatically increased. These alterations in tube mineralogy resulted in a holistic deterioration of the tube hardness and elasticity. Thus, in conditions where ΩA is near or below one, the aragonite-producing juvenile tubeworms may no longer be able to maintain the integrity of their calcification products, and may result in reduced survivorship due to the weakened tube protection.
Sandstone intervals of the Lower Goru Formation of the Cretaceous age are proven reservoir intervals in the middle Indus Basin, Pakistan. However, based on seismic data interpretation, it is difficult to differentiate payable gas sand from non-payable gas sand. Various types of post-stacks seismic attributes are extracted and analyzed to differentiate payable gas sand from non-payable. The analysis reveals that average instantaneous frequency, peak spectral frequency, average instantaneous phase and sweetness seem to be more effective attributes along with energy half time. Sweetness attribute map shows two sweet spot below the targeted window which indicate to the presence of gas play. Statistical analysis is also carried out to find the associations between seismic attributes and thickness of gas layer values. Cross plots of these attributes were quantified through regression analysis. A good correlation with regression coefficient (R 2 ) [ 0.78 is found between seismic attributes and gas layer thickness except average instantaneous phase attribute, which lays the foundation for predicting the thickness of gas reservoir.
Background:Diffusion-weighted imaging (DWI) with the intravoxel incoherent motion (IVIM) model has shown promising results for providing both diffusion and perfusion information in cervical cancer; however, its use to predict and monitor the efficacy of neoadjuvant chemotherapy (NACT) in cervical cancer is relatively rare. The study aimed to evaluate the use of DWI with IVIM and monoexponential models to predict and monitor the efficacy of NACT in cervical cancer.Methods:Forty-two patients with primary cervical cancer underwent magnetic resonance exams at 3 time points (pre-NACT, 3 weeks after the first NACT cycle, and 3 weeks after the second NACT cycle). The response to treatment was determined according to the response evaluation criteria in solid tumors 3 weeks after the second NACT treatment, and the subjects were classified as two groups: responders and nonresponders groups. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion-related pseudo-diffusion coefficient (D*), and perfusion fraction (f) values were determined. The differences in IVIM-derived variables and ADC between the different groups at the different time points were calculated using an independent samples t-test.Results:The D and ADC values were all significantly higher for the responders than for the nonresponders at all 3 time points, but no significant differences were observed in the D* and f values. An analysis of the receiver operating characteristic (ROC) curves indicated that a D value threshold <0.93 × 10−3 mm2/s and an ADC threshold <1.11 × 10−3 mm2/s could differentiate responders from nonresponders at pre-NACT time point, yielding area under the curve (AUC) of which were 0.771 and 0.806, respectively. The ROC indicated that the AUCs of D and ADC at the 3 weeks after the first NACT cycle and 3 weeks after the second NACT cycle were 0.823, 0.763, and 0.787, 0.794, respectively. The AUC values of D and ADC at these 3 time points were not significantly different (P = 0.641, 0.512, and 0.547, respectively).Conclusions:D and ADC values may be useful for predicting and monitoring the efficacy of NACT in cervical cancer. An IVIM model may be equal to monoexponential model in predicting and monitoring the efficacy of NACT in cervical cancer.
Human epidermal growth factor receptor‐2 (HER‐2) overexpression in breast tumor tissues is associated with a poor prognosis but may benefit from treatment with trastuzumab. The extracellular domain (ECD) of HER‐2 can be measured in serum and which has been a new inspection item in clinical laboratory of several hospitals. However, whether serum HER‐2 ECD can be a marker of HER‐2 status in tumor tissues still confused clinicians. This study is a retrospective observation to explore the correlation between serum HER‐2 ECD shedding and tissue HER‐2 status in breast cancer patients. Meanwhile, we will further uncover the potential clinical significance of serum HER‐2 ECD detection. A total of 545 unselected breast cancer patients from Fudan University Shanghai Cancer Center were enrolled in this study. At primary diagnosis without any treatment, serum HER‐2 ECD was measured on ADVIA Centaur assay; meanwhile, tissue HER‐2 from core needle biopsy was tested through immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). We showed that serum HER‐2 ECD concentration was related to tissue HER‐2 status. Nevertheless, 36.9% of patients with tissue HER‐2 overexpression had low levels of HER‐2 ECD shedding (<15 ng/mL) in serum. Here, we demonstrated that HER‐2 ECD shedding was also associated with protein expression and alpha‐secretase activity of a disintegrin and metalloproteinase 10 (ADAM10) using tumor tissues and cell lines. Progression‐free survival (PFS) data from breast cancer patients in TNM phase II and III with tissue HER‐2 IHC 3+ were analyzed using Kaplan‐Meier plotter. The patients with serum HER‐2 ECD above 15 ng/mL had lower progression‐free survival than those with serum HER‐2 ECD <15 ng/mL. Thus, serum HER‐2 ECD could be a biomarker to identify the subgroup of poorer outcome among HER‐2 overexpression breast cancer patients. Inhibition of ADAM10 activity may have potential therapeutic benefit for this most aggressive tumor subgroup.
Metasurfaces have shown unprecedented capabilities and flexibilities for optical wave manipulation, which provide a powerful platform for the integration and minimization of multifunctional optical devices. However, the realization of the multidimensional manipulation of harmonic waves generated by nonlinear metasurfaces is still a challenge due to the lack of a theoretical guidance. Here, an efficient design strategy of nonlinear metasurfaces based on the hydrodynamic model of the free electron dynamics is demonstrated to realize the full complex‐amplitude modulation of the second harmonic generation (SHG). As a proof concept, three multifunctional nonlinear metasurfaces are designed, in which both the amplitude and the phase of the SHG waves are efficiently and independently manipulated. With numerical and experimental validations, the proposed nonlinear metasurfaces can realize the spin‐selective SHG optical vortices with independent topological charges. The design strategy of nonlinear metasurfaces shall boost the applications of nonlinear metasurfaces in optical information, optical multifunctional integration, and so on.
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