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The Chang 7 continental shale oil reservoir is tight. The recovery factor is extremely low, the remaining oil is very high, and injecting water to improve oil recovery effectiveness is too hard. Therefore, in this paper, physical simulation experiments of CO2 huff-n-puff shale oil and NMR tests were conducted to study the cycle numbers and permeability on the recovery degree, as well as the characteristics of shale oil mobilization and the remaining oil micro distribution. The results showed that the cumulative oil recovery factors (ORFs) gradually increased in the natural logarithmic form, the single cycle ORFs decreased rapidly in exponential form with the huff-n-puff cycle number, and the biggest economic cycle numbers were between approximately 3 and 5. Furthermore, the higher the permeability, the higher the ORF, but the difference of ORF decreased between the two experimental samples with the cycles. In addition, the gap of production and recovery degree was large between the different scale pores, the ORF of macropores was 6–8 times that of micropores, and the final remaining oil was mainly distributed in the micropores, accounting for 82.29% of the total amount; meanwhile, the macropores comprised less than 0.5%. In the process of huff-n-puff, CO2 flowed into macropores, mesopores, and smallpores under the pressure differential effect, but a small amount of CO2 slowly diffused into micropores, resulting in the ORF of the former with more free oil being higher and the ORF of micropores with more adsorbed oil being lower. Therefore, promoting a better contact and reaction between CO2 and shale oil of micropores is one of the key ways to effectively develop the Chang 7 continental shale oil and enhance oil recovery. [ABSTRACT FROM AUTHOR]

Importance: Persisting or new thrombi in the distal arteries and the microcirculation have been reported to limit the benefits of successful endovascular thrombectomy for patients with acute ischemic stroke. It remains uncertain whether intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by thrombectomy improves outcomes among patients with ischemic stroke due to large vessel occlusion., Objective: To assess the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion., Design, Setting, and Participants: This investigator-initiated, randomized, open-label, blinded-end point trial was implemented at 35 hospitals in China, enrolling 535 patients with proximal intracranial large vessel occlusion presenting within 24 hours of time last known well, who achieved near-complete or complete reperfusion by endovascular thrombectomy and did not receive intravenous thrombolysis prior to the procedure. Recruitment took place between November 15, 2022, and March 29, 2024, with final follow-up on July 4, 2024., Interventions: Eligible patients were randomly assigned to the intra-arterial urokinase group (a single dose of intra-arterial 100 000 IU urokinase injected in the initial target territory; n = 267) or control group (without intra-arterial thrombolysis; n = 267)., Main Outcomes and Measures: The primary efficacy outcome was the percentage of patients achieving survival without disability (modified Rankin Scale score of 0 or 1) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours., Results: A total of 535 patients were enrolled (median age, 69 years; 223 [41.8%] female) and 532 (99.6%) completed the trial. The percentage of patients with survival without disability at 90 days was 45.1% (120/266) in the intra-arterial urokinase group and 40.2% (107/266) in the control group (adjusted risk ratio, 1.13 [95% CI, 0.94-1.36]; P = .19). Mortality at 90 days (18.4% vs 17.3%, respectively; adjusted hazard ratio, 1.06 [95% CI, 0.71-1.59]; P = .77) and incidence of symptomatic intracranial hemorrhage (4.1% vs 4.1%, respectively; adjusted risk ratio, 1.05 [95% CI, 0.45-2.44]; P = .91) were not significantly different between groups., Conclusions and Relevance: Among patients with acute ischemic stroke due to large vessel occlusion, adjunct intra-arterial urokinase after near-complete to complete reperfusion by endovascular thrombectomy did not significantly increase the likelihood of survival without disability at 90 days., Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2200065617.

Introduction: High palmitic acid (PA) levels trigger metainflammation, facilitating the onset and progression of chronic metabolic diseases. Recently, exosomes were identified as new inflammation mediators. However, the mechanism by which macrophage exosomes mediate PA-induced inflammation remains unclear., Objectives: To explore how PA induces metainflammation through macrophage exosomes., Methods: Exosomes secreted by RAW264.7 mouse macrophages stimulated with PA (Exos PA ) or not (Exos) were prepared by ultracentrifugation. The differential miRNAs between Exos PA and Exos were identified by high-throughput sequencing, and their targeted mRNAs and proteins were bioinformatically analyzed and verified by qPCR and western blot. Mouse macrophages and metabolic cells (AML-12 hepatocytes, C2C12 myocytes or 3T3-L1 adipocytes) were treated with Exos PA or Exos. The verified miRNAs and its targeted molecules related to inflammation were analyzed in recipient cells. Furthers, exosomes were prepared from primary peritoneal macrophages isolated from AIN93G diet-fed (Control PM-Exos) or HPD-fed (PA PM-Exos) mice. Control or PA PM-Exos were then tail vein injected (30 μg) into mice (n = 10), once a week for 2 weeks. The verified miRNA and its targets in blood, blood exosomes, and metabolic tissues were detected. Finally, measured the levels of miRNA, inflammatory factors, and fatty acids in the blood of 20 obese/overweight individuals and 20 healthy individuals., Results: Exo PA activate NF-κB signaling and enhance inflammatory enzyme/cytokine production in macrophages and metabolic cells. Exo PA enrich miR-3064-5p and target to inhibit IκBα as verified by exosome inhibitors and miR-3064-5p mimics and inhibitors. HPD elevates exosomal miR-3064-5p, macrophage exosomal miR-3064-5p, and inflammatory cytokine levels in mice circulation. PA PM-Exos from HPD-fed mice triggered inflammation in the circulation and metabolic tissues/organs of chow diet-fed mice. Overweight/obese individuals exhibit increased levels of circulating palmitoleic acid, exosomal miR-3064-5p, and high-sensitivity C-reactive proteins., Conclusions: Macrophage exosomes transferring miR-3064-5p to target IκBα and activate NF-κB signaling in metabolic cells is a mechanism of PA-induced metainflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Scope: Gut microbiota (GM) is involved in nonalcoholic steatohepatitis (NASH) development. Phytochemicals soyasaponins can prevent NASH possibly by modulating GM. This study aims to investigate the preventive bioactivities of soyasaponin monomers (SS-A 1 and SS-Bb) against NASH and explores the mechanisms by targeting GM., Methods and Results: Male C57BL/6 mice are fed with methionine and choline deficient (MCD) diet containing SS-A 1 , SS-Bb, or not for 16 weeks. Antibiotics-treated pseudo germ-free (PGF) mice are fed with MCD diet containing SS-A 1 , SS-Bb, or not for 8 weeks. GM is determined by 16S rRNA amplicon sequencing. Bile acids (BAs) are measured by UPLC-MS/MS. In NASH mice, SS-A 1 and SS-Bb alleviate steatohepatitis and fibrosis, reduce ALT, AST, and LPS in serum, decrease TNF-α, IL-6, α-SMA, triglycerides, and cholesterol in liver. SS-A 1 and SS-Bb decrease Firmicutes, Erysipelotrichaceae, unidentified-Clostridiales, Eggerthellaceae, Atopobiaceae, Aerococcus, Jeotgalicoccus, Gemella, Rikenella, increase Proteobacteria, Verrucomicrobia, Akkermansiaceae, Romboutsia, and Roseburia. SS-A 1 and SS-Bb alter BAs composition in liver, serum, and feces, activate farnesoid X receptor (FXR) in liver and ileum, increase occludin and ZO-1 in intestine. However, GM clearance abrogates the preventive bioactivities of SS-A 1 and SS-Bb against NASH., Conclusion: GM plays essential roles in soyasaponin's preventive bioactivities against steatohepatitis in MCD diet-induced NASH mice., (© 2024 Wiley-VCH GmbH.)

The multi-pass transmembrane protein ACCELERATED CELL DEATH 6 (ACD6) is an immune regulator in Arabidopsis thaliana with an unclear biochemical mode of action. We have identified two loci, MODULATOR OF HYPERACTIVE ACD6 1 (MHA1) and its paralog MHA1-LIKE (MHA1L), that code for ∼7 kDa proteins, which differentially interact with specific ACD6 variants. MHA1L enhances the accumulation of an ACD6 complex, thereby increasing the activity of the ACD6 standard allele for regulating plant growth and defenses. The intracellular ankyrin repeats of ACD6 are structurally similar to those found in mammalian ion channels. Several lines of evidence link increased ACD6 activity to enhanced calcium influx, with MHA1L as a direct regulator of ACD6, indicating that peptide-regulated ion channels are not restricted to animals., Competing Interests: Declaration of interests D.W. holds equity in Computomics, which advises breeders. D.W. advises KWS SE, a plant breeder and seed producer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Disorder of consciousness (DoC) is a clinical condition caused by severe brain damage. Some studies have reported that acupuncture, a traditional Chinese treatment, could facilitate the recovery of the patient's consciousness. The therapeutic effects of acupuncture may be due to its modulation of facilitating cortex (PFC) activity, but it has not been greatly demonstrated., Objectives: We intended to observe the effects of acupuncture on prefrontal cortical activity, explore the potential correlation between cortical activation and the severity of DoC, and analyze the functional brain network connectivity to provide a theoretical basis for its application in clinical practice., Methods: Participants diagnosed with DoC were included in the study. Before the intervention, we assessed the patient's state of consciousness using relevant scales, such as the Glasgow coma scale (GCS) and the coma recovery scale-revised (CRS-R). All patients received acupuncture manipulation with the functional near-infrared spectroscopy (fNIRS) system monitored., Result: A total of 16 subjects participated in our study. We observed that the concentration of oxygenated hemoglobin (HbO) in the PFC was increased during the acupuncture manipulation and declined during the resting state. Then, the connection strength of the left cerebral cortex was generally higher than that of the right. Finally, we observed only a weak difference in hemodynamic responses of PFC between the vegetative state (VS) and minimally conscious state (MCS) groups. However, the difference was not statistically significant., Conclusion: Our results indicated that acupuncture can increase the concentration of HbO in the PFC and strengthen the connection strength of the left cerebral cortex. However, our present study did not find a significant correlation between the cortical hemodynamic response and the severity of DoC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Wen Xin et al.)

Atherosclerosis is a chronic inflammatory disease causing coronary heart attacks and strokes. Soyasaponins (SS), the phytochemicals naturally existing in soybeans and their products, have been shown to reduce hypercholesterolemia and inflammation, which are intimately related to the genesis and development of atherosclerosis. However, the anti-atherosclerotic functionality of soyasaponins remains unknown. The aim of this study was to investigate the effects of the supplementation of two types of soyasaponin monomers (A1 and A2) on atherosclerotic plaque formation, serum lipid profiles, and inflammation in ApoE gene knockout (ApoE-/-) mice. Sixty 5-week-old ApoE-/- male mice were fed with a high-fat diet (HFD) and intervened by SSA1 and SSA2 (10 and 20 μmol per kg BW, respectively) or simvastatin (10 μmol per kg BW) for 24 weeks. The atherosclerotic lesions in the aorta, aortic root, and innominate artery, lipid profile and inflammatory markers in serum, and TLR4/MyD88/NF-κB signaling in arterial tissues were determined. SSA1 and SSA2 decreased the plaque ratio in the aortic root and innominate artery but not in the entire aorta. In serum, SSA1 reduced TG, TC, and LDL-C but increased HDL-C; SSA2 decreased TC, TG, and LDL-C but did not affect HDL-C. Meanwhile, SSA1 increased TG, SSA2 increased TC, and both of them increased bile acids in the feces. SSA1 and SSA2 lowered TNF-α, MCP-1, and hs-crp in serum. Furthermore, SSA1 and SSA2 reduced the TLR4 and MyD88 expressions in the aorta and innominate artery and inhibited NF-κB p65 and IκBα phosphorylation in the aorta. These results suggest that SSA1 and SSA2 exert anti-atherosclerotic functionalities by decreasing hypercholesterolemia and inflammation in HFD-fed ApoE-/- mice.