Important molecular mechanisms in ferroptosis.

Ferroptosis is a type of cell death that is caused by the oxidation of lipids and is dependent on the presence of iron. It was first characterized by Brent R. Stockwell in 2012, and since then, research in the field of ferroptosis has rapidly expanded. The process of ferroptosis-induced cell death is genetically, biochemically, and morphologically distinct from other forms of cellular death, such as apoptosis, necroptosis, and non-programmed cell death. Extensive research has been devoted to comprehending the intricate process of ferroptosis and the various factors that contribute to it. While the majority of these studies have focused on examining the effects of lipid metabolism and mitochondria on ferroptosis, recent findings have highlighted the significant involvement of signaling pathways and associated proteins, including Nrf2, P53, and YAP/TAZ, in this process. This review provides a concise summary of the crucial signaling pathways associated with ferroptosis based on relevant studies. It also elaborates on the drugs that have been employed in recent years to treat ferroptosis-related diseases by targeting the relevant signaling pathways. The established and potential therapeutic targets for ferroptosis-related diseases, such as cancer and ischemic heart disease, are systematically addressed.

Nitrate transformation and source tracking of Yarlung Tsangpo River using a multi-tracer approach combined with Bayesian stable isotope mixing model.

Excessive levels of nitrate nitrogen (NO3--N) could lead to ecological issues, particularly in the Yarlung Tsangpo River (YTR) region located on the Qinghai Tibet Plateau. Therefore, it is crucial to understand the fate and sources of nitrogen to facilitate pollution mitigation efforts. Herein, multiple isotopes and source resolution models were applied to analyze key transformation processes and quantify the sources of NO3-. The δ15N-NO3- and δ18O-NO3- isotopic compositions in the YTR varied between 1.23‰ and 13.64‰ and -7.88‰-11.19‰, respectively. The NO3--N concentrations varied from 0.08 to 0.86 mg/L in the dry season and 0.20-1.19 mg/L during the wet season. Nitrification remained the primary process for nitrogen transformation in both seasons. However, the wet season had a widespread effect on increasing nitrate levels, while denitrification had a limited ability to reduce nitrate. The elevated nitrate concentrations during the flood season were caused by increased release of NO3- from manure & sewage (M&S) and chemical fertilizers (CF). Future endeavors should prioritize enhancing management strategies to improve the utilization efficiency of CF and hinder the direct entry of untreated sewage into the water system.

Lipidomics profile and volatile compounds of squids (Illex argentinus, Ommastrephes Bartram and Dosidicus gigas) in the Argentine, North Pacific Ocean, Equator and Peru by UPLC-triple TOF-MS and HS-SPME-GC-O-MS.

Comprehensive lipid and volatile compound analyses were performed with squids collected from four varied geographical locations to discriminate the regional characteristics. A total of 1442 lipid molecules and 110 volatiles were detected in the squid muscle samples. There were significant differences in the lipid profiles between Argentine squid (Illex argentinus, AGT), North Pacific Ocean squid (Ommastrephes Bartram, NPO), Equatorial squid (Dosidicus gigas, EQ), and Peruvian squid (Dosidicus gigas, PR) muscle. Phosphatidylcholines (14.64%), triacylglycerols (12.42%), and ceramides (10.97%) were the main lipid components. The contents of polyunsaturated fatty acid in phospholipids and in glycerolipids were 30.35-52.05% and 18.11-25.15%, respectively. The volatiles in squids exhibited significant regional variation; 1-pentanol and 1-octanol, 2-ethyl-1-hexanol and terpinen-4-ol, 2,7-ethyl-1-hexanol, 3-methy-1-butanol and 2-propyl-1-pentanol were identified as characteristic flavor compounds in AGT, NPO, EQ, and PR, respectively. Sphingomyelin, phosphatidylserine, phosphatidylethanolamine, and ceramide were strongly correlated with volatiles in squid muscle. Our study is a reference for the lipid nutritional value and flavor compounds of squids.

Familial Resilience in Crisis: Navigating the Mediating Landscape of Depressive Symptoms Between Uncertainty Stress and Suicide Behavior Among Chinese University Students.

Background: Previous findings indicate that stress has a profound influence on suicide behavior, but the potential mediating and moderating mechanisms are unknown between uncertainty stress and suicide behavior. The present study, therefore, examined the relationship between uncertainty stress and suicide behavior, the mediating effect of depressive symptoms, and the moderating effect of family relationship in a sample of university students in China. Methods: 1828 university students were assessed anonymously by using the Uncertainty Stress Scale, Center for Epidemiologic Studies Depression Scale, Brief Suicidal Scale, and Family Relationship Scale between May to June in 2021. SPSS 26.0 was used for descriptive statistics and Spearman correlation analysis. PROCESS 3.5 was used to calculate the significance of the mediating and moderating effects of the variables. Results: Moderated mediation model analyses showed that: (a) depressive symptoms partially mediated the link between uncertainty stress and suicide behavior (indirect effect = 0.14, 95%bootstrap CI = 0.10, 0.19). The indirect effect of the depressive symptoms accounted for 67.12% of the total variance in suicide behavior. (b) The indirect association between uncertainty stress and suicide behavior was moderated by family relationship. Specifically, the paths from uncertainty stress to depressive symptoms (interact effect = -0.06, P<0.001) and depressive symptoms to suicide behavior (interact effect = -0.08, P<0.01) were weakened in the context of higher family relationship. Conclusion: Depressive symptoms play a crucial role in bridging uncertainty stress and suicide behavior, while the family relationship can buffer the mediation impact of depressive symptoms. These findings significantly contribute to the prevention and intervention of suicide in Chinese university students.

Optimizing rice yield, quality and nutrient use efficiency through combined application of nitrogen and potassium.

Reasonable nitrogen (N) and potassium (K) application rates can effectively improve fertilizer use efficiency, rice yield and quality. A two-year field experiment was conducted with combined application of three N rates (135, 180, and 225 kg ha-1, denoted as N1-N3) and four K rates (0, 90, 135, and 180 kg ha-1, denoted as K0-K3) using super indica hybrid rice cultivar Yixiangyou (YXY) 2115 to explore the effects of co-application of N and K on rice growth and development. The results indicated that the combined application of N and K had significantly interactive effects on dry matter (DM) accumulation, nutrients absorption, N harvest index (NHI), K harvest index (KHI), spikelets per panicle and most rice quality indexes. The highest total DM accumulation (17998.17-19432.47 kg ha-1) at maturity stage was obtained under N3K2. The effect of co-application of N and K on nutrients absorption and utilization varied between the two years and within each year. The highest total N and K accumulations at maturity stage were observed under N3K1 and N3K2, respectively, while the highest N recovery efficiency (NRE) and K recovery efficiency (KRE) were observed under N1K3. High expression levels of N and K metabolism-related genes in rice grains were observed under N3K2 or N3K3, consistent with N and K uptake. Co-application of N and K increased rice yield significantly and the highest yield (6745.02-7010.27 kg ha-1) was obtained under N2K2. As more N was gradually applied, rice appearance quality improved but milling, cooking and eating quality decreased. Although appropriate application of K could improve rice milling, cooking and eating quality, it reduced appearance quality. The optimal milling, cooking and eating quality were obtained under N1K2, while the best appearance quality was obtained under N3K0. Overall, a combination of 135-210 kg ha-1 N and 115-137 kg ha-1 K application rates was recommended for achieving relatively higher yield and better quality in rice production.

Responses of Yield and Photosynthetic Characteristics of Rice to Climate Resources under Different Crop Rotation Patterns and Planting Methods.

Climate is the most important environmental factor influencing yield during rice growth and development. To investigate the relationships between climate and yield under different crop rotation patterns and planting methods, three typical rotation patterns (vegetable-rice (V), rape-rice (R), and wheat-rice (W)) and two mechanical planting methods (mechanical transplanting (T1) and mechanical direct seeding (T2)) were established. The results showed that compared to the V rotation pattern, the average daily temperature (ADT) during the sowing to heading stage increased under both R and W rotation patterns, which significantly shortened the growth period. Thus, the effective accumulated temperature (EAT), photosynthetic capacity, effective panicle (EP), and spikelet per panicle (SP) under R and W rotation patterns significantly decreased, leading to reductions in grain yield (GY). VT2 had a higher ratio of productive tillers (RPT), relative chlorophyll content (SPAD), leaf area index (LAI), and net photosynthetic rate (Pn) than those of VT1, which significantly increased panicle dry matter accumulation (DMA), resulting in an increase in GY. Although RT2 and WT2 had a higher RPT than those of RT1 and WT1, the GY of RT1 and WT1 decreased due to the significant reductions in EAT and photosynthetic capacity. Principal component analysis (PCA) showed that the comprehensive score for different rotation patterns followed the order of V > R > T with VT2 ranking first. The structural equation model (SEM) showed that EAT and ADT were the most important climate factors affecting yield, with total effects of 0.520 and -0.446, respectively. In conclusion, mechanical direct seeding under vegetable-rice rotation pattern and mechanical transplanting under rape-rice or wheat-rice rotation pattern were the rice-planting methods that optimized the climate resources in southwest China.

Easily applicable predictive score for MPR based on parameters before neoadjuvant chemoimmunotherapy in operable NSCLC: a single-center, ambispective, observational study.

BACKGROUND: Neoadjuvant chemoimmunotherapy (NACI) is promising for resectable nonsmall cell lung cancer (NSCLC), but predictive biomarkers are still lacking. The authors aimed to develop a model based on pretreatment parameters to predict major pathological response (MPR) for such an approach. METHODS: The authors enrolled operable NSCLC treated with NACI between March 2020 and May 2023 and then collected baseline clinical-pathology data and routine laboratory examinations before treatment. The efficacy and safety data of this cohort was reported and variables were screened by Logistic and Lasso regression and nomogram was developed. In addition, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to assess its power. Finally, internal cross-validation and external validation was performed to assess the power of the model. RESULTS: In total, 206 eligible patients were recruited in this study and 53.4% (110/206) patients achieved MPR. Using multivariate analysis, the predictive model was constructed by seven variables, prothrombin time (PT), neutrophil percentage (NEUT%), large platelet ratio (P-LCR), eosinophil percentage (EOS%), smoking, pathological type, and programmed death ligand-1 (PD-L1) expression finally. The model had good discrimination, with area under the receiver operating characteristic curve (AUC) of 0.775, 0.746, and 0.835 for all datasets, cross-validation, and external validation, respectively. The calibration curves showed good consistency, and decision curve analysis indicated its potential value in clinical practice. CONCLUSION: This real world study revealed favorable efficacy in operable NSCLC treated with NACI. The proposed model based on multiple clinically accessible parameters could effectively predict MPR probability and could be a powerful tool in personalized medication.

Quantifying physiological health efficiency and benefit threshold of greenspace exposure in typical urban landscapes.

Although greenspace exposure has physiological health benefits, there is insufficient research on the threshold effect of health benefits in typical urban landscapes. Here we selected five typical urban landscapes (open greenspace, semi-closed greenspace, closed greenspace, bluespace, grey space) in 15 urban parks in Xiamen, China, and applied the physiological health threshold model to calculate the efficiency threshold and benefit threshold of greenspace exposure by continuously monitoring the changes of two physiological indicators-electroencephalography (EEG) and heart rate (HR). (1) The EEG threshold results show that compared with greenspace exposure, bluespace exposure can reach the physiological health efficiency threshold faster (4-5 min) but does not show an advantage in terms of benefit threshold. The more open the greenspace, the faster it can reach the efficiency threshold (5-6 min), but the higher the canopy density of the (closed) greenspace, the shorter the time to reach the efficiency threshold (8-9 min). (2) The HR threshold shows that bluespace and open greenspace are the fastest to reach the efficiency threshold (1 min), with the remaining greenspace reaching it after 6-7 min. The benefit threshold was reached faster in the bluespace (11 min) than in the greenspace (18-21 min), and the degree of openness of the greenspace has no significant effect on the speed of benefit thresholds. (3) Combining the results of EEG and HR thresholds, it can be seen that bluespace is better at reducing stress, while open greenspace can reach efficiency thresholds more quickly. This study confirms the physiological health threshold model, offering a reference for urban greenspace planning to enhance residents' stress management and health.

Corrigendum: Advances in oncolytic herpes simplex virus and adenovirus therapy for recurrent glioma.

[This corrects the article DOI: 10.3389/fimmu.2023.1285113.].

Mechanisms involved in the cytotoxic effects of berberine on human colon cancer HCT-8 cells

Berberine, a constituent of some traditional Chinese medicinal plants, has been reported to have cytotoxicity effects on different human cancer cell lines. There is no available information about the effects and mechanism of action of berberine on human colon cancer cell line HCT-8. In this paper, the cytotoxicity of berberine on HCT-8 cancer cells was investigated by MTT assay, fluorescence microscopy and flow cytometry analysis. Our data revealed that berberine could significantly inhibit the growth of HCT-8 cells in a dose- and time-dependent manner. Morphology of apoptotic cells was studied with acridine orange/ethidium bromide staining. The concentrations of lactate dehydrogenase and both acid and alkaline phosphatases were significantly increased in cell supernatants after berberine treatment, suggesting cell death. Furthermore, flow cytometry analysis showed that berberine could arrest HCT-8 cells at S phase in a time-dependent manner. To further investigate the apoptotic molecular mechanism, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting methods were used. The up-regulated mRNA and/or protein expressions of Fas, FasL, TNF-a, caspase-3 and down-regulation of pro-caspase-3 suggest that the death receptor pathway may be involved in the apoptotic pathway induced by berberine. Decrease of Bcl-2 and increase of Bax in mRNA and/or protein expressions showed that the Bcl-2 family proteins were involved in berberine-induced apoptosis. We also found that berberine-induced apoptosis was associated with an up-regulated expressions of p53 and prohibitin (PHB), and decreased vimentin expression. These results suggest that berberine can suppress cell growth and reduce cell survival by arresting the cell-cycle and by inducing apoptosis of HCT-8 cells.