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Glutathione plays a critical role in plant growth, development and response to stress. It is a major cellular antioxidant and is involved in the detoxification of xenobiotics in many organisms, including plants. However, the role of glutathione-dependent redox homeostasis and associated molecular mechanisms regulating the antioxidant system and pesticide metabolism remains unclear. In this study, endogenous glutathione levels were manipulated by pharmacological treatments with glutathione synthesis inhibitors and oxidized glutathione. The application of oxidized glutathione enriched the cellular oxidation state, reduced the activity and transcript levels of antioxidant enzymes, upregulated the expression level of nitric oxide and Ca2+ related genes and the content, and increased the residue of chlorothalonil in tomato leaves. Further experiments confirmed that glutathione-induced redox homeostasis is critical for the reduction of pesticide residues. RNA sequencing analysis revealed that miRNA156 and miRNA169 that target transcription factor SQUAMOSA-Promoter Binding Proteins (SBP) and NUCLEAR FACTOR Y (NFY) potentially participate in glutathione-mediated pesticide degradation in tomato plants. Our study provides important clues for further dissection of pesticide degradation mechanisms via miRNAs in plants. [Display omitted] • GSH-mediated redox signal regulates pesticide metabolism at transcriptional level. • GSSG increased cellular oxidation state and chlorothalonil residue in tomato leaves. • GSH maintains NO and Ca2+ levels and detoxification enzyme activity. • miRNAs participate in the GSH-mediated pesticide degradation in tomato plants. • GSH regulates miRNA156 and miRNA169 and their target transcription factors. [ABSTRACT FROM AUTHOR]

To establish an animal model of delayed intravenous resuscitation following seawater immersion after hemorrhagic shock (HS). Adult male SD rats were randomly divided into three groups: group NI (HS with no immersion), group SI (HS with skin immersion), and group VI (HS with visceral immersion). Controlled HS in rats was induced by withdrawing 45% of the calculated total blood volume within 30 min. In SI group, immediately after blood loss, 0.5 cm below the xiphoid process was immersed in artificial seawater, at (23 ± 1) °C, for 30 min. In VI group, the rats were performed by laparotomy and the abdominal organs were immersed in (23 ± 1) °C seawater for 30 min. Two hours after seawater immersion, the extractive blood and lactated Ringer's solution were delivered intravenously. The mean arterial pressure (MAP), lactate, and other biological parameters were investigated in different time points. The survival rate of 24 h after HS was recorded. After seawater immersion following HS, MAP and abdominal viscera blood flow decreased significantly, and the plasma levels of lactate and the organ function parameters were increased than the baseline. The above changes in VI group were more serious than those in SI and NI group, especially in myocardial and small intestine damage. The hypothermia, hypercoagulation, and metabolic acidosis were also observed after seawater immersion; the injury was more severely in VI group than that of SI group. However, the plasma levels of sodium, potassium, chlorine, and calcium in VI group were significantly higher than those before injury and in the other two groups. In the VI group, the level of plasma osmolality in instant, 2 h, and 5 h after immersion was 111%, 109%, and 108% of the SI group, respectively, all P < 0.01. The 24-h survival rate of VI group was 25%, which was significantly lower than that of SI group (50%) and NI group (70%), P < 0.05. The model fully simulated the key damage factors and field treatment conditions, reflected the effects of low temperature and hypertonic damage caused by seawater immersion on the severity and prognosis of naval combat wounds, and provided a practical and reliable animal model for the study of field treatment technology of marine combat shock. [ABSTRACT FROM AUTHOR]

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • 12 new diterpenoids were isolated from Pedilanthus tithymaloides. • Compounds 1 – 3 characterize an unusual tricyclo[10.3.0.02,9]pentadecane skeleton. • Compounds 4 – 8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. • Compounds 1 – 12 dramatically reversed multidrug resistance in cancer cells. • Compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function. Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1 – 3), and nine new jatrophane diterpenoids, pedilanins D-L (4 – 12), along with five known ones (13 – 17), were isolated from Pedilanthus tithymaloides. Compounds 1 – 3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4 – 8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1 – 12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 μ M. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance. [ABSTRACT FROM AUTHOR]

Exploring new blanching technology can help to deal with the challenge of better preservation of fruits and vegetables in food industry. In current work, vacuum-steam pulsed blanching (VSPB) was employed to ginger and its effect on peroxidase (POD) inactivation, drying behavior, texture profiles, microstructure, ultrastructure, phytochemicals (6, 8, 10-gingerols and 6-shagaol) and antioxidant capacity were investigated. Results showed that VSPB inactivated POD completely within 4 cycles. The starch granules gelatinized, the plasma membrane ruptured, the cell wall degraded and fractured gradually during the VSPB process under the action of thermal effect and pressure fluctuation, these changes further led to texture softening and shortening of drying time. Compared to the untreated ginger, VSPB reduced the drying time by 4.41%–22.79%. In the case of dried quality, it was found that the 6, 8, 10-gingerols, total phenolics and antioxidant capacity of dried products under three cycles blanching treatment were higher by 20.2%, 53.0%, 22.4%, 28.6%, 14.0% (DPPH), and 13.4% (FRAP) compared to that of the unblanched dried ginger. The findings in current work indicate VSPB is a promising technique for ginger as it enhances drying process and improve the dried quality through efficiently inactivating the enzymes, altering the texture, microstructure and ultrastructure. [Display omitted] • A new blanching technology, vacuum-steam pulsed blanching technology was developed. • VSPB enhanced ginger drying, phytochemical contents, antioxidant capacity. • Ultrastructural and microstructure observations clarified the mechanism of quality enhancement. • The effects of thermal and pressure fluctuation on ginger quality were considered. • The pressure and Temp of the steam and the core Temp of ginger were monitored. [ABSTRACT FROM AUTHOR]