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Summary: β‐Carotene 15,15′‐monooxygenase was isolated and purified from the intestinal mucosa of pigs, and then, it was applied to hydrolyse the pigment in soybean oil, and thus, vitamin A fortified soybean oil was obtained. The pig intestinal mucosal protein solution was purified to a specific activity of 2.487 × 10−4 U mg−1, maximum reaction velocity (Vmax) of 8.42 × 10−9 mol/h and Michaelis constant (Km) of 2.03 × 10−5 m. The protein solution had a molecular mass of 156 kDa by gel filtration. The sodium deoxycholate concentrations, optimum pH, Tween 40 amount and enzyme amount for vitamin A production in soybean oil were determined to be 6.0 mm, 8.0, 3.0% (w/v) and 0.2 U/mL enzyme, respectively. Under these conditions, β‐carotene 15,15′‐monooxygenase produced 14.65 mg/L vitamin A after 20 h, with a conversion yield of β‐carotene of 33.29% (w/w). Therefore, the nutrients in soybean oil were improved. β‐carotene 15,15′‐monooxygenase was isolated and purified from the intestinal mucosa of pigs, and then, it was applied to hydrolyse the pigment in soybean oil, and thus, vitamin A fortified soybean oil was obtained. [ABSTRACT FROM AUTHOR]

Cyclooxygenase‐2 (COX‐2), 5‐lipoxygenase (5‐LOX), and cytochrome P450 (CYP) 4A‐mediated arachidonic acid (AA) metabolism play an essential role in human inflammatory disorders. Blocking COX‐2 pathway would shunt AA metabolism to the other pathway, thereby decreasing the efficacy and exacerbating adverse effects. Here we demonstrated that reprogramming COX‐2, 5‐LOX, and CYP4A‐mediated AA metabolism in macrophages by salidroside (Sal) ameliorates monosodium urate (MSU) crystal‐induced inflammation. Compared with COX‐2 inhibitor celecoxib, Sal (80 mg/kg) presented a superior anti‐arthritic profile in MSU crystal‐treated rats, accompanied with the decreased expression of COX‐2, 5‐LOX, and CYP4A and production of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 20‐hydroxyeicosatetraenoic acid (20‐HETE) in the synovial fluid macrophages. Sal decreased representative M1 marker (iNOS and CD86, etc.) expression and M1 cytokine (TNF‐α and IL‐1β) production, whereas it increased M2 marker (CD206 and Arg‐1) expression and M2 cytokine (TGF‐β and IL‐10) production. The injection of conditioned medium from MSU crystal‐treated macrophages into the ankle joint of rats reproduced the gouty inflammation, which was attenuated by Sal. Mechanistically, down‐regulation of COX‐2, 5‐LOX, and CYP4A in the RAW264.7 and NR8383 macrophages by Sal skewed macrophage polarization away from the M1 phenotype, and thereby prevented neutrophil migration and chondrocyte degradation with STAT1 and NF‐κB inactivation. Conversely, overexpression of COX‐2, 5‐LOX, CYP4A or STAT1, or exogenous addition of IL‐1β or TNF‐α partially abolished these effects. Together, inhibition of COX‐2, 5‐LOX, and CYP4A in macrophages by Sal ameliorates MSU crystal‐induced inflammation through decreasing TNF‐α and IL‐1β production, and may serve as a novel therapeutic strategy. Reprogramming COX‐2, 5‐LOX and CYP4A‐mediated AA metabolism by salidroside ameliorates gouty arthritis through inhibition of macrophage M1 polarization via STAT1 and NF‐κB signaling. [ABSTRACT FROM AUTHOR]

To improve the development effect of Xinchang gas field in western Sichuan, a long lateral-section horizontal well pattern of three wells was deployed in the northern of Xinchang structure. Based on the analysis on reservoir geology characteristics, the well structures were optimized to two trips from three trips. These wells have the characteristics of long open hole, long lateral section, and large displacement. Through making the hole trajectory control measures, monitoring drag and torque, and optimizing drilling fluid, the drilling efficiency of the pattern wells has been greatly improved, cooperated with PDC bit during drilling, which provided precious experiences for drilling long lateral-section horizontal wells in mid-depth formation in western Sichuan. [ABSTRACT FROM AUTHOR]

In this paper, the esterification of phytosterol and free fatty acids (FFA) in rice bran oil (RBO) was studied using Novozym 435 in supercritical CO2. It was found that with the increase in CO2 filling pressure, the esterification reaction rate also increased. When the pressure exceeded the critical point, CO2 fluid had a great effect on phytosterol conversion. Therefore, enzymatic esterification deacidification was studied when the CO2 filling pressure was 8.0 MPa, the results showed that when the lipase dosage was 3.0%, the phytosterol concentration was 18.0%, the molecular sieve addition was 10.0%, and the esterification temperature was 78°C, after 41 hr the FFA content of RBO decreased to 1.1%, the phytosterol conversion rate reached 93.2%, and the vitamin E (VE) retention in the product was 80.0%. Therefore, the esterification by Novozymes 435 in supercritical CO2 could have several applications in fats and oils industry. Practical applications: Much research has been done on the interesterification of vegetable oil in order to produce edible fats and oils. The current study provides a reliable and simple method for the esterification of phytosterol and free fatty acids (FFA) in rice bran oil (RBO). The optimal operating conditions lead to high quality oil. The FFA content of RBO decreased to 1.1%, the phytosterol conversion rate reached 93.2%, and the VE content in the product was 80.0%. The esterification by Novozymes 435 in supercritical CO2 could be applied in fats and oils industry. [ABSTRACT FROM AUTHOR]

In this paper, the esterification of phytosterol and free fatty acids (FFA) in rice bran oil (RBO) was studied using Novozym 435 in supercritical CO2. It was found that with the increase in CO2 filling pressure, the esterification reaction rate also increased. When the pressure exceeded the critical point, CO2 fluid had a great effect on phytosterol conversion. Therefore, enzymatic esterification deacidification was studied when the CO2 filling pressure was 8.0 MPa, the results showed that when the lipase dosage was 3.0%, the phytosterol concentration was 18.0%, the molecular sieve addition was 10.0%, and the esterification temperature was 78°C, after 41 hr the FFA content of RBO decreased to 1.1%, the phytosterol conversion rate reached 93.2%, and the vitamin E (VE) retention in the product was 80.0%. Therefore, the esterification by Novozymes 435 in supercritical CO2 could have several applications in fats and oils industry. Practical applications: Much research has been done on the interesterification of vegetable oil in order to produce edible fats and oils. The current study provides a reliable and simple method for the esterification of phytosterol and free fatty acids (FFA) in rice bran oil (RBO). The optimal operating conditions lead to high quality oil. The FFA content of RBO decreased to 1.1%, the phytosterol conversion rate reached 93.2%, and the VE content in the product was 80.0%. The esterification by Novozymes 435 in supercritical CO2 could be applied in fats and oils industry. [ABSTRACT FROM AUTHOR]

A comprehensive understanding of ferroptosis signaling pathways significantly contributes to the advances in cancer ferrotherapy. Herein, we constructed a self-assembled prodrug nanosystem targeting system x c - , a key regulator for ferroptosis, to amplify the therapeutic efficacy of cancer ferrotherapy. The prodrug nanosystem is assembled between sulfasalazine (SSZ, a ferroptosis resistance inhibitor) and disulfide-bridged levodopa (DSSD) that can chelate Fe 2+ ions to form SSZ-Fe 2+ @DSSD, and the resulting nanoassembly can not only inhibit ferroptosis resistance, but also generate ROS in the tumor microenvironment. Whereas the prodrug nanosystem is stable in the physiological environment, it becomes unstable in the tumoral and intracellular reductive microenvironment, where the disulfide linkers are disrupted by high levels of glutathione (GSH), triggering the release of active Fe 2+ and SSZ. Under the Fenton reaction, the released Fe 2+ thus can induce ferroptosis, which is amplified by SSZ-mediated inhibition of ferroptosis resistance to synergistically improve the therapeutic efficacy of ferroptosis. Our study thus provides an innovative prodrug strategy to advance anticancer ferroptosis.

Checkpoint blockade therapy has been proven efficacious in lung cancer patients. However, primary/acquired resistance hampers its efficacy. Therefore, there is an urgent need to develop novel strategies to improve checkpoint blockade therapy. Here we tested whether dual inhibition of cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) by flavonoid melafolone improves program death 1 (PD-1) checkpoint blockade therapy through normalizing tumor vasculature and PD-1 ligand (PD-L1) downregulation. Virtual screening assay, cellular thermal shift assay, and enzyme inhibition assay identified melafolone as a potential inhibitor of COX-2 and EGFR. In Lewis lung carcinoma (LLC) and CMT167 models, dual inhibition of COX-2 and EGFR by melafolone promoted survival, tumor growth inhibition, and vascular normalization, and ameliorated CD8 + T-cell suppression, accompanied by the downregulation of transforming growth factor- β (TGF- β ), vascular endothelial growth factor (VEGF), and PD-L1 in the tumor cells. Mechanistically, dual inhibition of COX-2 and EGFR in lung cancer cells by melafolone increased the migration of pericyte, decreased the proliferation and migration of endothelial cells, and enhanced the proliferation and effector function of CD8 + T cells through VEGF, TGF- β , or PD-L1 downregulation and PI3K/AKT inactivation. Notably, melafolone improved PD-1 immunotherapy against LLC and CMT167 tumors. Together, dual inhibition of COX-2 and EGFR by melafolone improves checkpoint blockade therapy through vascular normalization and PD-L1 downregulation and, by affecting vessels and immune cells, may be a promising combination strategy for the treatment of human lung cancer., (Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.)