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Background: Ischemia/reperfusion (I/R) caused by ischemic stroke treatments leads to brain injury, and autophagy plays a role in the pathology. Astragaloside IV is a potential neuroprotectant, but its underlying mechanism on cerebral I/R injury needs to be explored. The objective of this study is to investigate the neuroprotective mechanism of Astragaloside IV against cerebral I/R injury. Methods: Middle cerebral artery occlusion method (MCAO) and oxygen and glucose deprivation/reoxygenation (OGD/R) method were used to simulate cerebral I/R injury in Sprague-Dawley (SD) rats and HT22 cells, respectively. The neurological score, 2,3,5-Triphe-nyltetrazolium chloride (TTC) staining, and transmission electron microscope were used to detect cerebral damage in SD rats. Cell viability and cytotoxicity assay were tested in vitro. Fluorescent staining and flow cytometry were applied to detect the level of apoptosis. Western blotting was conducted to examine the expression of proteins associated with autophagy. Results: This study found that Astragaloside IV could decrease the neurological score, reduce the infarct volume in the brain, and alleviate cerebral I/R injury in MCAO rats. Astragaloside IV promoted cell viability and balanced Bcl-2 and Bax expression in vitro, reduced the rate of apoptosis, decreased the expression of P62, and increased the expression of LC3II/LC3I in HT22 cells after OGD/R. Conclusions: These data suggested that Astragaloside IV plays a neuroprotective role by down-regulating apoptosis by promoting the degree of autophagy.

Highlights d YAP represses NR4A1 transcription and mitochondrial localization d NR4A1 mediates the pro-apoptotic function in response to Hippo signaling d NR4A1 promotes YAP degradation to augment Hippo signaling d YAP promotes liver regeneration and tumorigenesis by repressing NR4A1

This paper presents a new algorithm for ultrasonic particle image velocimetry (Echo PIV) for improving the flow velocity measurement accuracy and efficiency in regions with high velocity gradients. The conventional Echo PIV algorithm has been modified by incorporating a multiple iterative algorithm, sub-pixel method, filter and interpolation method, and spurious vector elimination algorithm. The new algorithms' performance is assessed by analyzing simulated images with known displacements, and ultrasonic B-mode images of in vitro laminar pipe flow, rotational flow and in vivo rat carotid arterial flow. Results of the simulated images show that the new algorithm produces much smaller bias from the known displacements. For laminar flow, the new algorithm results in 1.1% deviation from the analytically derived value, and 8.8% for the conventional algorithm. The vector quality evaluation for the rotational flow imaging shows that the new algorithm produces better velocity vectors. For in vivo rat carotid arterial flow imaging, the results from the new algorithm deviate 6.6% from the Doppler-measured peak velocities averagely compared to 15% of that from the conventional algorithm. The new Echo PIV algorithm is able to effectively improve the measurement accuracy in imaging flow fields with high velocity gradients.

Gross primary productivity (GPP) is the most important component of terrestrial carbon flux. Red-edge (680–780 nm) reflectance is sensitive to leaf chlorophyll content, which is directly correlated with photosynthesis as the pigment pool, and it has the potential to improve GPP estimation. The European Space Agency (ESA) Sentinel-2A and B satellites provide red-edge bands at 20-m spatial resolution on a five-day revisit period, which can be used for global estimation of GPP. Previous studies focused mostly on improving cropland GPP estimation using red-edge bands. In this study, we firstly evaluated the relationship between eight vegetation indices (VIs) retrieved from Sentinel-2 imagery in association with incident photosynthetic active radiation (PARin) and carbon flux tower GPP (GPPEC) across three forest and two grassland sites in Australia. We derived a time series of five red-edge VIs and three non-red-edge VIs over the CO2 flux tower footprints at 16-day time intervals and compared both temporal and spatial variations. The results showed that the relationship between the red-edge index (CIr, ρ 783 ρ 705 − 1 ) multiplied by PARin and GPPEC had the highest correlation (R2 = 0.77, root-mean-square error (RMSE) = 0.81 gC∙m−2∙day−1) at the two grassland sites. The CIr also showed consistency (rRMSE defined as RMSE/mean GPP, lower than 0.25) across forest and grassland sites. The high spatial resolution of the Sentinel-2 data provided more detailed information to adequately characterize the GPP variance at spatially heterogeneous areas. The high revisit period of Sentinel-2 exhibited temporal variance in GPP at the grassland sites; however, at forest sites, the flux-tower-based GPP variance could not be fully tracked by the limited satellite images. These results suggest that the high-spatial-resolution red-edge index from Sentinel-2 can improve large-scale spatio-temporal GPP assessments.

The present study aimed to identify which patients with adenomyoma would benefit from sparing the uterus and which patients should undergo a hysterectomy to avoid secondary surgery. Patients with pathology-proven adenomyoma admitted to Beijing Chao-Yang Hospital between November 2005 and November 2015 were retrospectively reviewed. Relief and reappearance of dysmenorrhea following laparoscopic adenomyomectomy were evaluated. All 49 patients (mean age, 40.6±5.2 years; age range, 26–51 years) presented with severe dysmenorrhea prior to surgery. Dysmenorrhea was identified to be relieved in 83.7% (41/49) of patients at the 6-month follow-up. No factors were revealed to have a significant effect on the surgical outcome. The median follow-up period was 4.6 (1–11) years; and 24.5% (12/49) of patients experienced recurrence of dysmenorrhea. Multivariate analysis identified preoperative serum cancer antigen 125 (CA 125) levels [hazard ratio (HR), 2.356; 95% confidence interval (CI), 1.271–3.570; P=0.011], postoperative gonadotropin-releasing hormone agonist (GnRH-a) treatment (HR, 0.540; 95% CI, 0.241–0.873; P=0.017) and accompanying endometriosis (HR, 2.182; 95% CI, 1.556–3.031; P=0.003) as independent risk factors for relapse. Laparoscopic adenomyomectomy is effective for alleviating dysmenorrhea in patients with adenomyoma. Patients with lower preoperative serum CA 125 levels without accompanying endometriosis benefited greater from adenomyomectomy compared with all other patients. Postoperative GnRH-a treatment strengthens therapeutic effects.

Definitive chemoradiotherapy is the standard of care for inoperable locoregionally advanced esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies have led to a paradigm shift in advanced, metastatic ESCC treatment; however, the effect of incorporating checkpoint inhibitors in the definitive management of ESCC is unclear. Tislelizumab is an anti-PD-1 antibody specifically engineered to minimize FcɣR binding on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The RATIONALE 311 study described here (BGB-A317-311; NCT03957590) is a registrational multicenter, double-blind, placebo-controlled, randomized, Phase III clinical trial designed to evaluate the efficacy and safety of tislelizumab combined with concurrent chemoradiotherapy in patients with inoperable localized ESCC.

Spatial heterogeneity is present in the land surface at every scale and is one of the key factors that introduces inherent uncertainty into simulations of land surface processes and parameter retrieval based on remotely sensed data. Because of a lack of understanding of the heterogeneous characteristics of global mixed pixels, few studies have focused on modeling and inversion algorithms in heterogeneous areas. This paper presents a parameterization scheme to describe land cover heterogeneity quantitatively by composition and boundary information based on high-resolution land cover products. Global heterogeneity features at the 1-km scale are extracted from the 'GlobeLand30' land cover dataset with a spatial resolution of 30 m. The composition analysis of global mixed pixels shows that only 35% of pixels over the land surface of Earth are covered by a single land cover type, namely, pure pixels, and only 25.8% are located in vegetated areas. Pixels mixed with water are more common than pixels mixed with any other non-vegetation type. The fragmentation analysis of typical biomes based on the boundary length shows that the savanna is the most heterogeneous biome, while the evergreen broadleaf forest is the least heterogeneous. Deciduous needleleaf forests are significantly affected by canopy height differences, while crop and grass biomes are less affected. Lastly, the strengths and limitations of the method and the application of the land cover heterogeneity characteristics extracted in this study are discussed.