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To achieve the efficient utilization of low-permeability tight sand and gravel reservoirs with strong heterogeneity in the Mahu oil area of Xinjiang, CO2 injection is used to improve oil recovery. The sweep pattern of the injected gas is closely related to the development of reservoir pores and throats. Firstly, a three-dimensional model of the average pore-throat radius was established based on complete two-dimensional nuclear magnetic resonance scanning data of the target layer’s full-diameter core in the Wuerhe Formation. Subsequently, an online NMR injection CO2 continuous oil displacement experiment was conducted using tight conglomerate rock cores to clarify the rules of CO2 oil displacement in each pore-throat interval. Finally, the three-dimensional pore-throat model was combined with microscopic utilization patterns to quantitatively characterize the reservoir utilization rate of the CO2 displacement oil and guide on-site dynamic analysis. The research results indicate that the reservoir space of the Wuerhe Formation is mainly composed of residual intergranular pores, accounting for 40.9% of the pores, followed by intragranular dissolution pores and shrinkage pores. The proportion of pore-throat coordination numbers less than 1 is relatively high, reaching 86.3%. The average pore-throat radius calculation model, established using online NMR data from the continuous coring of full-diameter cores, elucidates the characteristics of the average pore-throat radius in the Wuerhe Formation reservoir. Based on gas displacement experiments that explored the pore-throat behavior at the microscale, the calibrated CO2 injection oil recovery rate was determined to be 43.9%, and the proportion of reserves utilized within the main range during CO2 displacement amounted to 60.77%. The injection pressure is negatively correlated with the maximum pore-throat radius of the gas injection well group, and negatively correlated with the proportion of the 0.9~2 μm distribution of large pore throats in each gas injection well group.

To achieve the efficient utilization of low-permeability tight sand and gravel reservoirs with strong heterogeneity in the Mahu oil area of Xinjiang, CO[sub.2] injection is used to improve oil recovery. The sweep pattern of the injected gas is closely related to the development of reservoir pores and throats. Firstly, a three-dimensional model of the average pore-throat radius was established based on complete two-dimensional nuclear magnetic resonance scanning data of the target layer’s full-diameter core in the Wuerhe Formation. Subsequently, an online NMR injection CO[sub.2] continuous oil displacement experiment was conducted using tight conglomerate rock cores to clarify the rules of CO[sub.2] oil displacement in each pore-throat interval. Finally, the three-dimensional pore-throat model was combined with microscopic utilization patterns to quantitatively characterize the reservoir utilization rate of the CO[sub.2] displacement oil and guide on-site dynamic analysis. The research results indicate that the reservoir space of the Wuerhe Formation is mainly composed of residual intergranular pores, accounting for 40.9% of the pores, followed by intragranular dissolution pores and shrinkage pores. The proportion of pore-throat coordination numbers less than 1 is relatively high, reaching 86.3%. The average pore-throat radius calculation model, established using online NMR data from the continuous coring of full-diameter cores, elucidates the characteristics of the average pore-throat radius in the Wuerhe Formation reservoir. Based on gas displacement experiments that explored the pore-throat behavior at the microscale, the calibrated CO[sub.2] injection oil recovery rate was determined to be 43.9%, and the proportion of reserves utilized within the main range during CO[sub.2] displacement amounted to 60.77%. The injection pressure is negatively correlated with the maximum pore-throat radius of the gas injection well group, and negatively correlated with the proportion of the 0.9~2 μm distribution of large pore throats in each gas injection well group.

Microplastics (MPs), a brand-new class of worldwide environmental pollutant, have received a lot of attention. MPs are consumed by both humans and animals through water, food chain and other ways, which may cause potential health risks. However, the effects of MPs on embryonic development, especially placental function, and its related mechanisms still need to be further studied. We investigated the impact on fetal development and placental physiological function of pregnant mice by consecutive gavages of MPs at 0, 25, 50, 100 mg/kg body weight during gestational days (GDs 0–14). The results showed that continuous exposure to high concentrations of MP significantly reduced daily weight gain and impaired reproductive performance of pregnant mice. In addition, MPs could significantly induce oxidative stress and placental dysfunction in pregnant mice. On the other hand, MPs exposure significantly decreased placental barrier function and induced placental inflammation. Specifically, MPs treatment significantly reduced the expression of tight junction proteins in placentas, accompanied by inflammatory cell infiltration and increased mRNA levels of pro-inflammatory cytokines and chemokines in placentas. Finally, we found that MPs induced placental apoptosis and endoplasmic reticulum (ER) stress through the GRP78/IRE1α/JNK axis, leading to placental dysfunction and decreased reproductive performance in pregnant mice. We revealed for the first time that the effects of MPs on placental dysfunction in pregnant animals. Blocking the targets of MPs mediated ER stress will provide potential therapeutic ideas for the toxic effects of MPs on maternal pregnancy.

Androgen receptor splice variant 7 (AR-V7), a form of ligand-independent and constitutively activating variant of androgen receptor (AR), is considered as the key driver to initiate castration-resistant prostate cancer (CRPC). Because AR-V7 lacks ligand-binding domain, the AR-targeted therapies that aim to inactivate AR signaling through disrupting the interaction between AR and androgen are limited in CRPC. Thus, the emergence of AR-V7 has become the greatest challenge for treating CRPC. Targeting protein degradation is a recently proposed novel avenue for cancer treatment. Our previous studies have been shown that the oncoprotein AR-V7 is a substrate of the proteasome. Identifying novel drugs that can trigger the degradation of AR-V7 is therefore critical to cure CRPC. Here we show that nobiletin, a polymethoxylated flavonoid derived from the peel of Citrus fruits, exerts a potent anticancer activity via inducing G0/G1 phase arrest and enhancing the sensitivity of cells to enzalutamide in AR-V7 positive PC cells. Mechanically, we unravel that nobiletin selectively induces proteasomal degradation of AR-V7 (but not AR). This effect relies on its selective inhibition of the interactions between AR-V7 and two deubiquitinases USP14 and USP22. These findings not only enrich our understanding on the mechanism of AR-V7 degradation, but also provide an efficient and druggable target for overcoming CRPC through interfering the stability of AR-V7 mediated by the interaction between AR-V7 and deubiquitinase.

Experiments were conducted to investigate the cavitation behavior of Helmholtz self-sustained oscillation jets. In this paper, highspeed photographic technology was used to capture the flow details of cavitation with various nozzle structures and operating pressures from 1.0 MPa to 3.0 MPa. Furthermore, an in-house code based on a matrix approach that processes gray values with various statistical methods was used to quantitatively evaluate the cavitation jet of waters generated by Helmholtz nozzles. The mean values of the normalized gray levels of the images were used as a metric to measure the lengths of the cavitation clouds. When the original data were smoothed by a 15th lowess filter to exclude the noise of the images, the periods of cavitation cloud shedding were obtained accordingly, and the average period had a magnitude of 10 -4 . All of the smoothed results of the original data captured a two-peak shape that comprises a large peak and a mild hump. Image processing results showed that the Helmholtz nozzle produced greater cavitation intensity than a traditional conical nozzle. The shear-layer instability waves disappeared within 10 d 1 downstream from the injector exit. The cavitation clouds propagated a distance of approximately 1–10 d 1 at various pressure ratios, and the clouds were continuous within this distance. The geometry of the nozzle strongly affected the length and shedding period of the cavitation cloud. As described in the discussion section of this paper, when the cavity length was doubled, the length of the cavitation cloud decreased approximately 26.5 %; however, the period of the cavitation cloud shedding increased approximately 10 %. The longest cavitation cloud appeared when the ratio of the cavity diameter and the upper nozzle diameter was eight. Excessively small or large diameters were not conducive to the development of cavitation, whereas the effect of the pressure ratio on the cavitation cloud length was positive. When other conditions remained unchanged, the lump shedding period decreased as the pressure ratio was increased to 25. When the pressure ratio exceeded 25, the cavitation cloud shedding period remained constant.

Climate change has caused a widespread deduction in terrestrial water storage (TWS), leading to ocean water mass gains and sea level rises. A better understanding of how the land–sea water mass has been redistributed can help with the scientific response to climate change. However, there are few studies investigating the roles of the different physical processes involved in low-frequency land–sea water mass redistribution on a global scale. To address this issue, in this study, a comprehensive investigation was carried out with respect to the globally distributed key factors causing low-frequency ocean mass anomalies during the period 2004–2021. Global water mass redistribution data, derived from GRACE/GRACE-FO satellite gravity and surface wind and sea-surface temperature data from ERA5 reanalysis, were employed, and the empirical orthogonal function, maximum covariance analysis, and sea-level equation approaches were used. The results show that the long-term trend and decadal-like fluctuation are two major components of the low-frequency land–sea water mass redistribution. The wind-forcing dynamic processes significantly drive the anomalies near the North Indian Ocean, North Atlantic Ocean, South Pacific Ocean, and some marginal seas, where variance explanations range from 30% to 97%. After removing the ocean dynamics, the residual ocean mass anomaly is mostly explained by sea-level fingerprints (SLFs), especially in the open ocean. The 25th, 50th, and 75th percentiles of the SLF-explained variances in all ocean grids are 59%, 72%, and 82%, respectively. Some non-negligible noise, located in seismic zones, was also found, suggesting the misestimation of seafloor deformation resulting from earthquakes in the GRACE/GRACE-FO data processing. These findings may improve our understanding of the long-term anomalies in regional and global sea levels.

The emergence of new highly pathogenic and drug-resistant influenza strains urges the development of novel therapeutics for influenza A virus (IAV). Here, we report the discovery of an anti-IAV microbial metabolite called APL-16-5 that was originally isolated from the plant endophytic fungus Aspergillus sp. CPCC 400735. APL-16-5 binds to both the E3 ligase TRIM25 and IAV polymerase subunit PA, leading to TRIM25 ubiquitination of PA and subsequent degradation of PA in the proteasome. This mode of action conforms to that of a proteolysis targeting chimera which employs the cellular ubiquitin-proteasome machinery to chemically induce the degradation of target proteins. Importantly, APL-16-5 potently inhibits IAV and protects mice from lethal IAV infection. Therefore, we have identified a natural microbial metabolite with potent in vivo anti-IAV activity and the potential of becoming a new IAV therapeutic. The antiviral mechanism of APL-16-5 opens the possibility of improving its anti-IAV potency and specificity by adjusting its affinity for TRIM25 and viral PA protein through medicinal chemistry. Here, Zhao et al. characterize the anti-viral effect of the compound APL-16-5, which is originally derived from the plant endophytic fungus Aspergillus, on Influenza A virus infection in vitro and in vivo. They find that APL-16-5 binds to the E3 ligase TRIM25 and viral polymerase subunit PA and therewith mediates ubiquitination of PA and subsequent proteasome-mediated degradation.’

Prostate cancer (PC) is the second most common cancer with limited treatment option in males. Although the reactivation of embryonic signals in adult cells is one of the characteristics of cancer, the underlying protein degradation mechanism remains elusive. Here, we show that the molecular chaperone GRP75 is a key player in PC cells by maintaining the protein stability of SIX1, a transcription factor for embryonic development. Mechanistically, GRP75 provides a platform to recruit the deubiquitinating enzyme USP1 to inhibit K48-linked polyubiquitination of SIX1. Structurally, the C-terminus of GRP75 (433-679 aa) contains a peptide binding domain, which is required for the formation of GRP75-USP1-SIX1 protein complex. Functionally, pharmacological or genetic inhibition of the GRP75-USP1-SIX1 protein complex suppresses tumor growth and overcomes the castration resistance of PC cells in vitro and in xenograft mouse models. Clinically, the protein expression of SIX1 in PC tumor tissues is positively correlated with the expression of GRP75 and USP1. These new findings not only enhance our understanding of the protein degradation mechanism, but also may provide a potential way to enhance the anti-cancer activity of androgen suppression therapy.

The high-energy density of supercapacitors is urgently needed. In this work, we develop a high energy density hierarchical ZnCo 2 S 4 /ZnCo 2 O 4 electrode material with flower-like structure directly anchored on nickel foam by hydrothermal and ion exchange method. The as-prepared hierarchical arrays take advantage of ZnCo 2 S 4 with high electroactive surface area, flower-like morphology with rapid channels for ion diffusion and electron transport. ZnCo 2 O 4 possesses good stability and cooperativity with ZnCo 2 S 4 . Remarkably, the ZnCo 2 S 4 /ZnCo 2 O 4 delivers a specific capacitance of 1057.78 F g −1 at the current density of 1 A g −1 in a three-electrode system. An asymmetric supercapacitor (ASC) was assembled with ZnCo 2 S 4 /ZnCo 2 O 4 as positive electrode and carbon nanotubes (CNTs) as negative electrode, delivers a high energy density of 127.4 W h kg −1 at a power density of 2520 W kg −1 and a long cycle life (89% of capacity retention after 5000 cycles). The assembled ASC can work as a power source, which can drive the fan after being charged.

Large amount of inhalation of the radon exacerbates the risk of cancer in the human body, and human beings also pay more attention to the problem of environmental pollution. With the increasing mining of underground mineral resources, coal production has increased significantly, but at the same time, it has also increased the number of underground goaf, and it has also seriously increased the potential danger of spontaneous combustion in the goaf. The influence of thermal effect on pore structure and radon exhalation characteristics was studied by means of relevant measurement. The outcomes confirmed that the radon exhalation characteristics of fly ash increased linearly with the increase of temperature and then decreased exponentially. At 400 °C, the radon exhalation rate of fly ash is the highest, which is 8.41 Bq m −2 h −1 , 2.11 times that of fly ash at normal temperature. This is closely related to the change in pore structure of fly ash after heat treatment. The research results in this study are significant for assessing the radiation risk of radon in fly ash.