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• Baicalein can inhibit cisplatin-induced renal tubular epithelial cell inflammation and ferroptosis in acute kidney injury (AKI) both in vivo and in vitro. • 12-Lipoxygenase promotes ferroptosis in cisplatin-induced AKI. • 3. 12-Lipoxygenase is the key molecule of baicalein in inhibiting renal tubular epithelial cell ferroptosis in AKI. In acute kidney injury (AKI), ferroptosis is the main mechanism of cell death in the renal tubular epithelium. Baicalein, a traditional Chinese medicine monomer, plays a protective role in various kidney diseases; however, the effect of baicalein on ferroptosis in AKI still needs further exploration. In this study, we explored the role of baicalein and its specific mechanism in mediating ferroptosis in cisplatin-induced AKI. We used a cisplatin-induced AKI model to study the effects of baicalein on renal tissue and tubular epithelial cell injury. The effects of baicalein on tubular epithelial cell ferroptosis were detected in cisplatin-induced AKI and further verified by folic acid-induced AKI. The Swiss Target Prediction online database was used to predict the possible mechanism by which baicalein regulates ferroptosis, and the specific target proteins were further verified. Molecular docking and SPR were used to further determine the binding potential of baicalein to the target protein. Finally, RNA interference (RNAi) technology and enzymatic inhibition were used to determine whether baicalein regulates ferroptosis through target proteins. Baicalein alleviated cisplatin- and folic acid-induced renal dysfunction and pathological damage and improved cisplatin-induced HK2 cell injury. Mechanistically, baicalein reduced the expression of 12-lipoxygenase (ALOX12), which inhibits phospholipid peroxidation and ferroptosis in AKI. Molecular docking and SPR demonstrated direct binding between baicalein and ALOX12. Finally, we found that silencing ALOX12 had a regulatory effect similar to that of baicalein. Comparable results were also obtained with the ALOX12 inhibitor ML355. This was the first study to confirm that baicalein regulates ferroptosis both in vitro and in vivo in cisplatin-induced AKI and to verify the regulatory effect of baicalein in folic acid-induced AKI. Our results reveal the critical role of ALOX12 in kidney damage and ferroptosis caused by cisplatin and emphasize the regulatory effect of baicalein on renal tubular epithelial cell ferroptosis mediated by ALOX12. Baicalein is an effective drug for treating AKI, and ALOX12 is a potential drug target. [ABSTRACT FROM AUTHOR]

[Display omitted] • The EH of the YRB has slightly improved in the last two decades, but it is still not optimistic. • There is a significant nonlinear correlation between EH and impact factors. • The importance of anthropogenic factors on EH increased significantly, while the intensity of natural factors decreased. • Targeted ecological protection and restoration measures were proposed. Identifying the dominant factors influencing ecosystem health and their optimal thresholds is essential for the management and restoration of ecosystems. Most of the works, however, have less detected the importance level of individual factors, especially their changes over time and scale, and rarely determined their threshold effects on ecosystem health (EH), which seriously hinders the formulation of targeted policies for sustainable ecosystem management. To address these research gaps, we present an innovative visualization approach to reveal importance changes in natural and anthropogenic variables and their nonlinear coupling process with EH in the China's Yellow River Basin (YRB) in the last two decades. Results show that (i) Although the EH in the YRB has improved slightly in the past 20 years, it is still not optimistic and shows distinct spatial heterogeneity. (ii) The impact of human activities on the ecosystem health of the YRB has increased and increasingly plays a decisive role, while that of the natural aspect has decreased recently. Specifically, environmental factors (slope, NDVI, and annual temperature) are the dominant factors affecting the upstream EH. Midstream EH is significantly affected by the synergistic effect of natural and anthropogenic factors, but the importance of the proportion of built-up land is intensified (ranked from 8th to 4th). Anthropogenic factors exert the greatest influence on downstream EH variation, especially for population density whose importance order rising from 7th to 2nd. (iii) By illustrating the nonlinear response curves of EH at multi-scale, the tipping point caused ecosystem deterioration in the YRB is explored and the optimal thresholds of leading factors oriented towards the most effective ecosystem conservation goal are obtained. These results help precisely identify the current health status of YRB's ecosystem, as well as providing a valuable reference for moderate restoration standards and sustainable ecosystem management. [ABSTRACT FROM AUTHOR]

Ferritin, the principal iron storage protein, is essential to iron homeostasis. How iron homeostasis affects the adipose tissue is not well understood. We investigated the role of ferritin heavy chain in adipocytes in energy metabolism. We generated adipocyte-specific ferritin heavy chain (Fth , also known as Fth1) knockout mice, herein referred to as Fth AKO . These mice were analyzed for iron homeostasis, oxidative stress, mitochondrial biogenesis and activity, adaptive thermogenesis, insulin sensitivity, and metabolic measurements. Mouse embryonic fibroblasts and primary mouse adipocytes were used for in vitro experiments. In Fth AKO mice, the adipose iron homeostasis was disrupted, accompanied by elevated expression of adipokines, dramatically induced heme oxygenase 1(Hmox1) expression, and a notable decrease in the mitochondrial ROS level. Cytosolic ROS elevation in the adipose tissue of Fth AKO mice was very mild, and we only observed this in the brown adipose tissue (BAT) but not in the white adipose tissue (WAT). Fth AKO mice presented an altered metabolic profile and showed increased insulin sensitivity, glucose tolerance, and improved adaptive thermogenesis. Interestingly, loss of ferritin resulted in enhanced mitochondrial respiration capacity and a preference for lipid metabolism. These findings indicate that ferritin in adipocytes is indispensable to intracellular iron homeostasis and regulates systemic lipid and glucose metabolism. • Fth deletion reduces total iron but increases labile iron, accompanied by induction of some antioxidant genes. • Adipocyte Fth knockout mice exhibit an altered energy metabolism profile, with a preference for fat metabolism to glucose. • Adipocyte Fth knockout mice significantly excel in insulin sensitivity and glucose tolerance tests. [ABSTRACT FROM AUTHOR]

This study aimed to assess the influence of educational level on the recurrence rate and number of stroke episodes in stroke survivors. For this cross-sectional study, information regarding patient characteristics, medical history, ability to perform activities of daily living, level of disability, number of episodes, and stroke recurrence was collected. Analyses were conducted using the chi-square test, analysis of variance, nonparametric test, Cox regression model, and the Kaplan-Meier method. Of the 696 stroke survivors enrolled in this study, the average stroke recurrence rate was 20.83 %, and the recurrence rates in patients with primary (or lower), secondary, and university (or higher) education were 26.58, 19.54 and 14.29 %, respectively. Patients with primary (or lower) or secondary education had a higher risk for stroke recurrence than those with a university education or higher. We found that the recurrence rate 10 years after an initial stroke was higher than that after 5 years. Moreover, there was a statistically significant difference in the cumulative recurrence rate among the three groups (χ2 = 9.36, P < 0.05). Lastly, the proportions of the number of stroke episodes differed between the various education level groups (P < 0.05). A lower educational level was shown to be a risk factor for stroke recurrence and education levels have an impact on the number of stroke episodes. Our results suggest that is necessary to strengthen post-stroke management and rehabilitation interventions for patients with low educational levels. [ABSTRACT FROM AUTHOR]

Two-stage programming (TSP) is popular in resources planning management, especially for limited and precious resources. Remarkable study has been done to improve the model performance. However, one of the biggest obstacle is lack of objectivity when it comes to penalty quantification derived from recourse behavior. Besides, much attention has been paid in the resources deficiency penalty but little in resources residual, which may lead to wasting. In order to clarify the physical meaning of mathematical equation for recourse penalty from both resources scarcity and surplus, the production frontier was estimated and the technical efficiency and shadow prices of resources were introduced into TSP to characterize the resources deficiency and residual penalty, respectively. Then, an intuitionist fuzzy interval two-stage stochastic programming (IFITSP) was generated integrating the uncertainty of fuzzy membership and traditional TSP. An integrated solving approach was proposed coupling several previous uncertain programming methods and an improved robust interval TSP method. A case study was conducted in an arid area of northwest China to schedule agricultural cultivation scale based on limited water resources. The inefficiencies were [0.26, 0.49], [0.14, 0.37] and [0, 0.03] for GZ, LZ, and GT. The shadow prices of GZ, LZ, and GT in 2015 were 12.94, 2.61, 2.67 Yuan/m3 respectively, indicating the sever water crisis of GZ. The relatively unbiased and abundant decision could be generated by the developed IFITSP to help decision makers with various preferences make tradeoff between benefits and basic crop production requirement as well as balance resources deficiency and surplus. The results also show that the developed model could unveil the uncertainty influence of model inputs on decision strategies and trigger managers to deeply analyze subjective effect and associated risk. By comparison, the proposed methodology can not only clarify the physical meaning of penalty but deal with more complex uncertainty than previous methods. Therefore, the established model can provide reliable and scientific support for resources planning with recourse. • Production frontier was estimated to help clarify the physical meaning of recourse penalty in two-stage programming (TSP). • An intuitionist fuzzy interval TSP was generated involving multiple uncertainties. • An integrated solving approach was proposed including an improved method for interval TSP. • A case study of planning cultivated area based on limited water resources was demonstrated. • The established methodology can be widely applied to resources planning management. [ABSTRACT FROM AUTHOR]

Abstract This study presents an inexact joint-probabilistic double-sided stochastic chance-constrained programming (IJDSCCP) model for sustainable water resources planning and pollution control in water quality management systems under uncertainty. Techniques of interval parameter programming (IPP), joint-probabilistic programming (JPP) and double-sided stochastic chance-constrained programming (DSCCP) are incorporated into a modeling framework. The IJDSCCP can not only address uncertainties presented as interval parameters and double-sided randomness (i.e. both left-hand and right-hand sides) that are characterized as normal distributions, but also examine the reliability level of satisfying the entire system constraints. It further improves upon conventional stochastic chance-constrained programming for handing random uncertainties in the left-hand and right-hand sides of constraints. Moreover, a non-equivalent but sufficient linearization form of the IJDSCCP is presented to solve such a problem. Then, the model is applied to a representative case for water resources planning and pollution control. The results including water resources planning solutions, pollution control plans and system benefits under the combinations of different joint and individual probability levels will be obtained. The solutions are expressed as combinations of deterministic, interval and distributional information, which can facilitate analysis of different forms of uncertainties. After investigating and comparing the variations of results, it is found that an increasing joint probability level can lead to higher system benefits, i.e., [13,841.68, 21,801.81] × 106 Yuan (p = 0.01, p 1 = 0.0033, p 2 = 0.0033 and p 3 = 0.0033), [14,150.26, 22,260.06] × 106 Yuan (p = 0.05, p 1 = 0.0166, p 2 = 0.0166 and p 3 = 0.0166) and [14,280.55, 22,415.52] × 106 Yuan (p = 0.10, p 1 = 0.033, p 2 = 0.033 and p 3 = 0.033). A set of decreased individual probability levels gives rise to the maximum system benefits at the same joint probability level. Furthermore, the results of the IJDSCCP are compared with a general interval-based optimization framework as well. Therefore, the results from the IJDSCCP are valuable for assisting managers in generating and identifying decision alternatives under different scenarios. Graphical abstract Unlabelled Image Highlights • An inexact joint-probabilistic double-sided stochastic chance-constrained programming model is developed. • A non-equivalent but sufficient linearization form of the developed model is presented. • An increasing joint probability level leads to higher system benefits. • A set of decreased individual probability levels results in the maximum system benefits at the same joint probability level. [ABSTRACT FROM AUTHOR]

Battery preheating at low temperatures is essential to ensure the efficient operation of electric vehicles in all climate conditions. Alternating current heating is proposed as an effective preheating method to improve the poor performance of lithium-ion batteries operated at low temperatures. To describe the dynamic voltage behavior accurately, the Butler-Volmer equation has been employed, and then a novel electro-thermal coupled model has been proposed for accurately calculating the thermal behavior of a battery. To obtain the optimal preheating performance, the electro-thermal coupled model-based available heating current computational method has been developed to obtain the optimal echelon preheating strategy. This method has the potential to balance the heat generation rate and degradation on battery lifetime. Finally, the proposed echelon heating strategy has been verified by battery cells and battery packs. Results show that the battery cell can be heated from the temperature of −20.3 °C to 10.02 °C by 13.7 min with an average temperature-rise 2.21 °C/min. And the battery pack can be heated from −20.84 °C to 10 °C by 12.4 min with an average temperature-rise is 2.47 °C/min. [ABSTRACT FROM AUTHOR]