Activation of the p62-Keap1-Nrf2 pathway protects against oxidative stress and excessive autophagy in ovarian granulosa cells to attenuate DEHP-induced ovarian impairment in mice.

Di-(2-ethylhexyl) phthalate (DEHP) is widely used in various plastics but has been demonstrated to cause female reproductive toxicity. However, the exact mechanism underlying the ovarian damage induced by DEHP remains unclear. In this study, DEHP was administered orally to 5-week-old female mice for 30 days at doses of 0, 250, 500, and 1000 mg/kg/day. The findings demonstrated that DEHP exposure disrupted ovarian function and follicular development as well as induced oxidative stress and autophagy in ovarian granulosa cells (GCs). Further, 200 µM mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP in vivo, induced autophagy in both human ovarian granulosa cells line (KGN) and mouse primary GCs within 24 h in vitro. However, it did not affect the p62-dependent autophagy flux. Furthermore, MEHP-induced autophagy was inhibited by the autophagy inhibitor 3-MA and exacerbated by the autophagy activator rapamycin, indicating that MEHP induces excessive autophagy in GCs. Subsequently, we found that MEHP-induced autophagic cell death was primarily attributed to oxidative damage from elevated intracellular ROS levels. Meanwhile, MEHP exposure induced nuclear translocation of erythroid-derived factor 2-related factor (Nrf2), a key regulator of antioxidant activity resulting in activating antioxidant effects. Interestingly, we also found that MEHP-induced increase in p62 competitively binds Keap1, thereby facilitating nuclear translocation of Nrf2 and establishing a positive feedback loop in antioxidant regulation. Therefore, this study demonstrated that inhibition of Nrf2 could aggravate oxidative damage and enhance excessive autophagy caused by MEHP, while activation of Nrf2 could reverse the trend. These findings have also been reinforced in studies of cultured ovaries in vitro. Our study suggests that the p62-Keap1-Nrf2 pathway may serve as a potential protective mechanism against DEHP-induced oxidative stress and excessive autophagy in mouse GCs.

Research on Lateral Resistance Performance of Prestressed Cross-Laminated Timber-Concrete Composite Structures under Reciprocating Loads.

Cross-Laminated Timber (CLT) and concrete composite structures represent an architectural system that integrates the strengths of both materials. In this innovative configuration, the CLT and concrete collaborate synergistically, harnessing their individual merits to achieve enhanced structural performance and functionality. Specifically, the CLT offers a lightweight design, superior bending resistance, and immense engineering plasticity, while concrete boasts exceptional compressive strength and durability. This study investigates the mechanical performance of CLT-concrete composite structures through quasi-static reciprocating loading tests in three full-scale CLT shear wall samples. Designed with varying initial prestressing forces and dimensions of the CLT panel, the prestressed CLT-concrete structures demonstrated a reduced dependence on the steel nodes, resulting in an increase in yield load, yield displacement, and maximum load-carrying capacity. Maximum capacity increased by 39.8% and 33.7% under initial prestressing forces of 23 kN and 46 kN on steel strands. Failure occurred due to localized compressive failure on prestressed steel strands and anchor plates. ABAQUS finite element analysis established three refined models, revealing that the increased initial prestressing force moderately enhanced stiffness but reduced ductility under similar cross-sectional dimensions. Furthermore, under consistent CLT material, dimensions, prestressing force, and loading conditions, prestressed CLT-concrete structures exhibited a higher maximum load-bearing capacity than prestressed CLT-steel composite structures. This study proposes structural design recommendations based on experimental and simulation results, incorporating specific assumptions.

Molecular basis for insecticide-enhanced thermotolerance in the brown planthopper Nilaparvata lugens Stål (Hemiptera:Delphacidae).

Climate change is likely to have marked ecological effects on terrestrial ecosystems, including the activities of insect pests. Most attention has focused on the increasing geographical ranges of pests; however, if extrinsic factors enhance their thermotolerance, populations may express increased voltinism and longer daily and annual activity periods. These changes in pest populations have the potential for severe consequences, including increased crop losses and decreased food security at the global level. The brown planthopper (BPH) Nilaparvata lugens Stål (Hemiptera: Delphacidae) is a serious pest of rice crops in temperate and tropical regions of Asia. It is often present in rice microclimates at temperatures close to its maximum thermotolerance. Recent BPH outbreaks in tropical Asia are considered to be associated with excess use of pesticides and increasing temperature. This study tested whether exposure to sublethal concentrations of triazophos (tzp), an insecticide widely used in Asian rice production, enhances thermotolerance of BPH. Tzp exposure (40 ppm at 40 °C) significantly decreased mortality (from 94% in controls to 50% at 48 h post-treatment) and increased lethal mean time (LT50 ) of adults by 17.2 h. To investigate the underlying molecular mechanism of this tzp-enhanced thermotolerance, we selected Hsp70 and Arginine kinase (Argk) for detailed study. Transcripts encoding both proteins in third-instar nymphs and brachypterous adult females were up-regulated, compared with controls, after exposure to tzp. RNAi silencing of both genes demonstrated that Hsp70 and Argk are essential for survival and tzp-increased thermotolerance. We propose that tzp induces thermotolerance in BPHs by increasing the expression of genes that act in cell protection mechanisms. The significance of our proposal relates to the importance of understanding the influence of sublethal concentrations of insecticides on pest biology. In addition to its influence on thermotolerance, tzp also enhances BPH reproduction. We infer that exposure to a pesticide stressor can produce cross-tolerance, that is, increased tolerance to one stressor also increases tolerance to other stressors, including temperature. Aside from needing a better understanding of these effects in nature and in other pest/cropping systems, we suggest that pest management programmes can be improved with better understanding of the influences of stressors, including increased environmental temperatures and sublethal concentrations of insecticides, on pest biology.

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) alleviate excessive autophagy of ovarian granular cells through VEGFA/PI3K/AKT/mTOR pathway in premature ovarian failure rat model.

BACKGROUND: Premature ovarian failure (POF) is one of the leading causes of female infertility and is accompanied by abnormal endocrine, seriously affecting female quality of life. Previous studies have demonstrated that mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for POF. However, the mechanism remains obscure. This study aims to investigate the therapeutic effect of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on ovarian function in the POF rat model and explore the underlying mechanisms. METHODS: The ovarian function was evaluated by ovarian morphology, histology, estrous cycle, hormone levels (AMH, E2, FSH, and LH), and fertility ability to investigate the effect of hUC-MSCs on the POF rats model. The cytokines levels were assayed in serum using protein array to explore the mechanisms of hUC-MSCs therapy for POF. The excessive autophagy levels were evaluated using a co-culture system of 3D MSCs spheroids with human ovarian granulosa cell line (KGN) or primary ovarian granulosa cells (GCs) to understand the paracrine effect of hUC-MSCs on GCs. The related proteins expression of autophagy and PI3K/AKT/mTOR pathway was detected using Western Blotting and/or in various inhibitors supplement to further demonstrate that vascular endothelial growth factor A (VEGFA) secreted by hUC-MSCs can alleviate excessive autophagy of ovarian GCs via PI3K/AKT/mTOR signaling pathway. The ovarian culture model in vitro was applied to confirm the mechanism. RESULTS: The ovarian function of POF and the excessive autophagy of ovarian GCs were restored after hUC-MSCs transplantation. The protein array result demonstrated that VEGF and PI3K/AKT might improve ovarian function. in vitro experiments demonstrated that VEGFA secreted by hUC-MSCs could decrease oxidative stress and inhibit excessive autophagy of ovarian GCs via PI3K/AKT/mTOR pathway. The ovarian culture model results confirmed this mechanism in vitro. CONCLUSION: The hUC-MSCs can alleviate excessive autophagy of ovarian GCs via paracrine VEGFA and regulate the PI3K/AKT/mTOR signaling pathway, thereby improving the ovarian function of POF.

Sputtering of Molybdenum as a Promising Back Electrode Candidate for Superstrate Structured Sb2 S3 Solar Cells.

Sb2 S3 is rapidly developed as light absorber material for solar cells due to its excellent photoelectric properties. However, the use of the organic hole transport layer of Spiro-OMeTAD and gold (Au) in Sb2 S3 solar cells imposes serious problems in stability and cost. In this work, low-cost molybdenum (Mo) prepared by magnetron sputtering is demonstrated to serve as a back electrode in superstrate structured Sb2 S3 solar cells for the first time. And a multifunctional layer of Se is inserted between Sb2 S3 /Mo interface by evaporation, which plays vital roles as: i) soft loading of high-energy Mo particles with the help of cottonlike-Se layer; ii) formation of surficial Sb2 Se3 on Sb2 S3 layer, and then reducing hole transportation barrier. To further alleviate the roll-over effect, a pre-selenide Mo target and consequentially form a MoSe2 is skillfully sputtered, which is expected to manipulate the band alignment and render an enhanced holes extraction. Impressively, the device with an optimized Mo electrode achieves an efficiency of 5.1%, which is one of the highest values among non-noble metal electrode based Sb2 S3 solar cells. This work sheds light on the potential development of low-cost metal electrodes for superstrate Sb2 S3 devices by carefully designing the back contact interface.

Cultivar and insecticide applications affect the physiological development of the brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae).

Nilaparvata lugens (Stål) (Hemiptera:Delphacidae) is a serious migratory pest of rice in Asia. Pest resurgence often occurs because of insecticide overuse. Using both susceptible (TN1) and moderately resistant (Xieyou 963) cultivars, we studied the effect of foliar insecticides on the percentage of brachypterous adults, female reproductive rate, and crude fat and soluble sugar contents in third- and fifth-instar nymphs and adults. The percentage of brachypterous adults and reproductive rate of adult females developed from nymphs that fed on insecticide-treated plants varied significantly with rice cultivar, type of insecticide, and its concentration. Feeding on susceptible plants increased the percentage of brachypterous adults and reproductive rate of adult females. Also, deltamethrin increased brachypterous production relative to imidacloprid and triazophos. The highest reproductive rate was on plants treated with triazophos. All insecticide treatments in both cultivars resulted in increase of soluble sugar contents in third- and fifth-instar nymphs and adults developed from nymphs feeding on insecticide-treated rice plants. This effect was stronger on the susceptible cultivar. Changes of crude fat content after N. lugens feeding on insecticide-treated plants were related to its feeding duration. Crude fat content in adult developed from nymphs feeding on treated plants was significantly higher that on control plants. These studies showed that plant and insecticide influences on physiological ecology of this planthopper will influence its population dynamics under commercial production of rice in Asia.

Changes in levels of juvenile hormone and molting hormone in larvae and adult females of Chilo suppressalis (Lepidoptera: Pyralidae) after imidacloprid applications to rice.

Insect hormones regulate growth and development and fecundity of insects. The current study investigated changes in juvenile hormone (JH) and molting hormone (MH) levels in fourth instars and adult females of Chilo suppressalis (Walker) (Lepidoptera: Pyralidae) after imidacloprid application to rice, Oryza sativa L. The results showed that JH level in fourth instars that developed feeding on Fengyouxiangzhan rice plants sprayed with 15, 30, and 60 ppm imidacloprid was significantly higher than that of larvae that developed on control plants, increasing by 5.04, 6.39, and 4.89 times, respectively. The relationships between JH level and imidacloprid concentrations showed a significant negative correlation. In contrast, molting hormone (MH) level in larvae fed on control plants was significantly higher than that on treated plants. JH:MH values in fourth instars developed from larvae feeding on rice plants treated with 15, 30, 60, 80, and 100 ppm imidacloprid increased by 49.17, 39.43, 13.48, 15.80, and 0.2 times, respectively, compared with control. JH and JH:MH ratio in larvae fed on Wujing 15 plants treated with imidacloprid were significantly lower than those fed on Fengyouxiangzhan under the same treatments. JH level in adult females that developed from larvae feeding on rice plants sprayed with imidacloprid significantly decreased with increase in imidacloprid concentration, but it increased compared with control. JH level in adult females was associated with times of imidacloprid application. JH level in adult females developed from larvae feeding on rice plants after double spray with 30 ppm imidacloprid was significantly higher than control, increasing by 61.6 and 116.5%, respectively, compared with a single spray and the control. Moreover, hormone levels in the larvae were related to the application method of imidacloprid. JH level in fourth instars after root application and topical application of imidacloprid was significantly lower than in control. Thus, the dynamics of JH and MH in insects after insecticide applications are an extremely interesting problem, because hormones are related to insect growth and development.

Driving Pest Insect Populations: Agricultural Chemicals Lead to an Adaptive Syndrome in Nilaparvata Lugens Stål (Hemiptera: Delphacidae).

The brown planthopper (BPH) is a devastating pest of rice throughout Asia. In this paper we document the BPH biogeographic range expansion in China over the 20-year period, 1992 to 2012. We posed the hypothesis that the range expansion is due to a syndrome of adaptations to the continuous presence of agricultural chemicals (insecticides and a fungicide) over the last 40 years. With respect to biogeography, BPH ranges have expanded by 13% from 1992 to 1997 and by another 3% from 1997 to 2012. In our view, such expansions may follow primarily from the enhancing effects of JGM, among other agricultural chemicals, and from global warming. JGM treatments led to increased thermotolerance, recorded as decreased mortality under heat stress at 40 ± 1 °C (down from 80% to 55%) and increased fecundity (by 49%) at 34 °C. At the molecular level, JGM treatments led to increased abundances of mRNA encoding Acetyl Co-A carboxylase (Acc) (up 25%) and Hsp70 (up 32%) in experimental BPH. RNAi silencing of Hsp70 and Acc eliminated the JGM effects on fecundity and silencing Hsp70 reduced JGM-induced thermotolerance. Integrated with global climate change scenarios, such syndromes in pest insect species have potential for regional- and global-scale agricultural disasters.