Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice. / Nrf2ä»‹å¯¼çš„ç”Ÿç²¾ç»†èƒžé“æ­»äº¡å‚ä¸Žäº†èšè‹¯ä¹™çƒ¯çº³ç±³å¡‘æ–™å¯¼è‡´çš„å°é¼ é›„æ€§ç”Ÿæ®–æ¯’æ€§.

Microplastics (MPs) and nanoplastics (NPs) have become hazardous materials due to the massive amount of plastic waste and disposable masks, but their specific health effects remain uncertain. In this study, fluorescence-labeled polystyrene NPs (PS-NPs) were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo. Interestingly, whole-body imaging found that PS-NPs accumulated in the testes of mice. Therefore, the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice, and their mechanisms, were investigated. After oral exposure to PS-NPs, their spermatogenesis was affected and the spermatogenic cells were damaged. The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing (RNA-seq) to determine the toxic mechanisms; a ferroptosis pathway was found after PS-NP exposure. The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1 (Fer-1), and it was also found that nuclear factor erythroid 2-related factor 2 (Nrf2) played an important role in spermatogenic cell ferroptosis induced by PS-NPs. Finally, it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity. This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

A novel perspective on di-hexyl phthalate (2-ethylhexyl)-induced reproductive toxicity in females: Lipopolysaccharide synergizes with mono-2-ethylhexyl ester to cause inflammatory apoptosis rather than autophagy in ovarian granulosa cells.

Di-hexyl phthalate (2-ethylhexyl) (DEHP) has been confirmed to cause female reproductive toxicity in humans and model animals by affecting the survival of ovarian granulosa cells (GCs), but the interrelationships between DEHP's on autophagy, apoptosis, and inflammation in GCs are not clear. Our previous study demonstrated that DEHP exposure resulted in the disturbance of intestinal flora associated with serum LPS release, which in turn led to impaired ovarian function. LPS has also been shown to determine cell fate by modulating cellular autophagy, apoptosis, and inflammation. Therefore, this study investigated the role and link between LPS and autophagy, apoptosis, and inflammation of GCs in DEHP-induced ovarian injury. Here, we constructed an in vivo injury model by continuous gavage of 0-1500 mg/kg of DEHP in female mice for 30 days and an in vitro injury model by treatment of human ovarian granulosa cells (KGN) cells with mono-2- ethylhexyl ester (MEHP, an active metabolite of DEHP in vivo). In addition, the expression of relevant pathway molecules was detected by immunohistochemistry, immunofluorescence, qRT-PCR, and Western blotting after the addition of the autophagy inhibitor 3-methyladenine (3-MA), the apoptosis inhibitor Z-VAD- FMK and the NF-κB inhibitor BAY11-7082. The current study found that autophagy and apoptosis were significantly activated in GCs of DEHP-induced atretic follicles in vivo and found that MEHP-induced KGN cells autophagy and apoptosis were independent and potentially cytotoxic of each other in vitro. Further studies confirmed that DEHP exposure resulted in LPS release from the intestinal tract and entering the ovary, thereby participating in DEHP-induced inflammation of GCs. In addition, we found that exogenous LPS synergized with MEHP could activate the NF-κB signaling pathway to induce inflammation and apoptosis of GCs in a relatively prolonged exposure condition. Meanwhile, inhibition of inflammatory activation could rescue apoptosis and estrogen secretion function of GCs induced by MEHP combined with LPS. These results indicated that the increased LPS influenced by DEHP might cooperate with MEHP to induce inflammatory apoptosis of GCs, an important cause of ovarian injury in mice.

Comprehensive effects of microplastics on algae-laden surface water treatment by coagulation-ultrafiltration combined process: Algae cultivation, coagulation performance and membrane fouling development.

In coastal areas, the surface water has been simultaneously exposed to the algae blooms caused by eutrophication and the microplastics (MPs) pollution originating from active human activities. As a practical alternative to address these issues in drinking water plant, coagulation-ultrafiltration combined process is still confronted with the limited understanding about the comprehensive effects of MPs on algae-laden surface water (ASW) treatment. Considering the migration of MPs in nature environment and drinking water treatment process, this study first aims to systematically investigate the influence of MPs on algae cultivation, coagulation performance and membrane fouling development. The results of algae cultivation indicate that MPs stimulated the algae activity by 58 % and then constantly suppressed the secretion of protein-like, humic-like and polysaccharide-like metabolites. The variation of particle size distribution and zeta potential confirm that MPs acted as nuclei to facilitate the development of large coagulation flocs with an increasing average size from 82.6 µm to 107.6 µm, during which the negatively charged pollutants were neutralized and removed from ASW. According to the SEM images, MPs could destroy the structure of fouling layer on 50 kDa membranes during the filtration of ASW coagulation effluent. Its synergistic effect with the enhanced coagulation performance and the suppressed EOM secretion contributed to the alleviation of membrane fouling caused by overlapped large-sized foulants. However, the interaction between the enriched organic foulants by MPs and the deposited coagulants on 300 kDa membranes facilitated the development of cake layer, leading to the deterioration of membrane permeability. This study emphasizes the importance in concerning the existence of MPs during the treatment of ASW by coagulation-ultrafiltration combined process and their exact influence in water purification efficiency.

[Lead Removal from Water by Calcium-containing Biochar with Saturated Phosphate].

Calcium-containing biochar （ES-BC） was prepared by pyrolyzing eggshell and kitchen wastes， and the ES-BC composite was used to remove phosphate （marked as ES-BC/P）. Based on the high affinity of phosphate and carbonate to lead， the ES-BC/P was then used to remove lead from the water. The results showed that， in the appropriate dosage， ES-BC/P could remove lead efficiently at different initial concentrations （1-100 mg·L-1）， and the removal efficiency could reach to 99%. Meanwhile， the release of phosphorus could be ignored after the reaction. As ES-BC/P was alkaline， and the lead-containing solution was weakly acidic， the addition of ES-BC/P could adjust the pH of the system automatically. The reaction kinetics and isotherm experiments showed that the lead removal by ES-BC/P was mainly monolayer chemisorption with a maximum adsorption capacity of 493.12 mg·g-1 （318 K）. The characterization results showed that lead was mainly removed through the ion exchanges of Pb2+ in the solution with Ca2+ in ES-BC/P. Then， the Pb2+ combined with CO32- and PO42- to form many precipitates， including Pb5（PO4）3OH， Pb10（PO4）6（OH）2， PbCO3， and Pb3（CO3）2（OH）2. In summary， the ES-BC/P material could achieve the efficient removal of lead from the water， thereby realizing the resource utilization of the wastes.

Electrocoagulation enhanced gravity driven membrane bioreactor for advanced treatment of rural sewage.

The daily discharge of rural sewage in China occupies 30 % of the national wastewater discharge, and developing an energy-efficient, easy to operate, and decentralized rural sewage treatment technology becomes an important task. In this work, a novel rural sewage treatment technology, Electrocoagulation enhanced Gravity-Driven Membrane Bioreactor (EC-GDMBR) was exploited for the rural sewage treatment under long-term operation (160 days). Two EC-GDMBRs with various module structures of ceramic membrane (horizontal module and side module) not only displayed the desirable effluent quality, but also sustained the stable flux (8-13 LMH). The electrocoagulation, electrooxidation, biodegradation, and separation in EC-GDMBRs were able to synergistically remove the particle matter, organic (CODCr effluent <11.6 ± 1.2 mg/L) and nutrients (NH3-N effluent <0.1 mg/L, TN effluent <8.5 mg/L, TP effluent <0.05 mg/L). Besides, the high permeability of ceramic membrane and large porosity of biofilm on its surface improved the sustainability of stable flux during the long-term operation. Moreover, by analyzing bacterial abundance, Extracellular Polymeric Substances, Adenosine Tri-Phosphate and Confocal Laser Scanning Microscopy, a large number of microorganisms grew and accumulated on the carrier, as well as formed the biofilm (23.46-659.9 µm), while Nitrobacteria (1.6-4.1 %) and Nitrate (0.01-0.06 %) exited in the carrier biofilms, promoting the nitrogen removal. Compared with EC-GDMBR with side module of ceramic membrane, EC-GDMBR with horizontal module of ceramic membrane has advantages in flux behavior, organic/nutrient removal, microbial abundance/activity, abundance of nitrogen removal functional bacteria and water permeability of biofilm, because the ceramic membrane of horizontal module can promote the uniform growth of biofilm and improve the uniformity of flow penetration distribution. In general, the findings of this work verify the reliability of EC-GDMBR for the sustainable operation of wastewater treatment and improve its application value of rural sewage treatment.

Enhanced electrooxidation/electrocoagulation-ultrafiltration membrane process with S2O42- for saline algae-containing surface water treatment: Purification and membrane performance.

The surface water in coastal areas involving algae, is often affected by saline and emerging contaminants caused by saltwater intrusion, and expanding aquaculture industry. Therefore, it is necessary to conduct studies to address the issues that affect ecological safety and health of aquatic environments. This study presents the development of an enhanced electrooxidation/electrocoagulation-ultrafiltration (EO/EC-UF) membrane process using S2O42- (DTN@EO/EC-UF) for the treatment of saline water containing algae. Our results have shown that significant removal of NH3-N (95.1 %), UV254 (89.4 %) and algae (75.7 %) was achieved with the addition of S2O42- (DTN). Additionally, an optimal DTN dosage of 40 mg/L was used in the DTN@EO/EC process to enhance water purification, utilizing reactive species such as SO4·- and ·OH. After coupling with the ultrafiltration (UF) process, optimal operating conditions (DTN: 40 mg/L, current density: 4.65 mA/cm2, electrolysis: 60 s) were applied to treat the saline algae-containing surface water. The generated free chlorine, including NHCl2, accounted for approximately 22 % (0.14 mg/L). In addition, DTN significantly improved the ceramic membrane's permeability and anti-fouling characteristics, with a maximum increasing specific flux from 0.76 to 0.93, mainly attributing to the reduced the irreversible fouling resistance. Furthermore, we discovered that common membrane cleaning using acid or base enhanced the DTN@EO/EC-UF process. In conclusion, this study established an innovative DTN@EO/EC-UF process with excellent performance in terms of water purification and membrane self-cleaning. The results provided a promising alternative for treating saline algae-containing surface water.

Performance analysis of OSSK-UWOC systems considering pointing errors and channel estimation errors.

In this paper, we present the bit error rate (BER) performance of the underwater wireless optical communication (UWOC) systems using the optical space shift keying (OSSK) on the gamma-gamma turbulent fading channel, which also considers pointing errors and channel estimation errors. Firstly, we develop the new expressions for the probability density function (PDF) based on the Gamma-Gamma distribution with error factors. Subsequently, we analyze the statistical characteristic of the difference in attenuation coefficients between two channels in the OSSK system, by which we provide analytical results for evaluating the average BER performance. The results show that the effective improvement of spectral efficiency (SE) and BER performance is achieved by rationally allocating the number of lasers and detectors in the system. The OSSK-UWOC system performs better when a narrow beam waist is used. Furthermore, the presence of channel estimation error brings the BER performance advantage to the system, and the system with a high channel estimation error (ρ = 0.7) shows a 4 dB improvement in signal-to-noise ratio (SNR) gain compared to the system with a low channel estimation error (ρ = 0.95). The findings in this paper can be used for the UWOC system design.

Transmission characteristics of Gaussian array beams in seawater-to-air propagating incorporating turbulence media and foam layer.

This paper investigates the propagation of Gaussian array beams (GABs) through seawater-to-air in the presence of oceanic turbulence, atmospheric turbulence, and wave foams. Specifically, we focus on the intensity distribution of diverse typical GAB structures (ring, multi-ring, and rectangle). Then, an innovative intensity analysis model to calculate the average intensity in each medium is proposed. Moreover, we experimentally verify the proposed method by examining the intensity fading characteristic of Gaussian beams in the seawater-to-air path. Our results show that the peak intensity is primarily affected by the refraction in the ocean and foam layer, rather than air layer. The difference of theoretical and experimental values are less than 0.13 for the peak intensity. Moreover, the intensity distributions are more significantly affected by ocean turbulence but less influenced by wind speed.

Farnesoid X Receptor Protects Murine Lung Against IL-6-promoted Ferroptosis Induced by Poly(I:C).

Various infections trigger a storm of pro-inflammatory cytokines, in which IL-6 acts as a major contributor and leads to diffuse alveolar damage in patients. However, the metabolic regulatory mechanisms of IL-6 in lung injury remain unclear. Polyriboinosinic-polyribocytidylic acid (poly(I:C)) activates pattern recognition receptors involved in viral sensing and is widely used in alternative animal model of the RNA virus-infected lung injury. In this study, a intratracheal instillation of poly(I:C) with or without IL-6 neutralizing antibody model combined with metabonomics, transcriptomics and so on to explore the underlying molecular mechanisms of IL-6-exacerbated lung injury. We found that poly(I:C) increased IL-6 level, and the up-regulated IL-6 further induced lung ferroptosis, especially in AT2 cells. Meanwhile, the lung regeneration was impaired. Mechanistically, metabolomics analysis showed that poly(I:C) significantly decreased glycolytic metabolites and increased bile acid intermediate metabolites that inhibited the bile acid nuclear receptor farnesoid X receptor (FXR), which could be reversed by IL-6 neutralizing antibody. In ferroptosis microenvironment, IL-6 receptor monoclonal antibody, tocilizumab increased FXR expression, and subsequently increased Yes-associated protein (YAP) level by enhancing PKM2 in A549 cells. FXR agonist GW4064 and liquiritin, a potential natural herbal ingredient as FXR regulator, significantly attenuated lung tissue inflammation and ferroptosis while promoting pulmonary regeneration. Together, present study provides the evidence that IL-6 promotes ferroptosis and impairs regeneration of AT2 cells during poly(I:C)-induced murine lung injury by regulating the FXR-PKM2-YAP axis. Targeting FXR represents a promising therapeutic strategy for IL-6-associated inflammatory lung injury.

Photo-Assisted Li-N2 Batteries with Enhanced Nitrogen Fixation and Energy Conversion.

Li-N2 batteries have received widespread attention for their potential to integrate N2 fixation, energy storage, and conversion. However, because of the low activity and poor stability of cathode catalysts, the electrochemical performance of Li-N2 batteries is suboptimal, and their electrochemical reversibility has rarely been proven. In this study, a novel bifunctional photo-assisted Li-N2 battery system was established by employing a plasmonic Au nanoparticles (NPs)-modified defective carbon nitride (Au-Nv -C3 N4 ) photocathode. The Au-Nv -C3 N4 exhibits strong light-harvesting, N2 adsorption, and N2 activation abilities, and the photogenerated electrons and hot electrons are remarkably beneficial for accelerating the discharge and charge reaction kinetics. These advantages enable the photo-assisted Li-N2 battery to achieve a low overpotential of 1.32 V, which is the lowest overpotential reported to date, as well as superior rate capability and prolonged cycle stability (≈500 h). Remarkably, a combination of theoretical and experimental results demonstrates the high reversibility of the photo-assisted Li-N2 battery. The proposed novel strategy for developing efficient cathode catalysts and fabricating photo-assisted battery systems breaks through the overpotential bottleneck of Li-N2 batteries, providing important insights into the mechanism underlying N2 fixation and storage.

From stability to reliability: Unveiling the un-biased reference genes in porcine ovarian granulosa cells under different conditions.

Selection of optimal reference genes (RGs) is fundamental for functional genomics studies and gene expression analysis, which are two main approaches to identify functional genes and their expression patterns. However, no systematic study has identified the suitable RGs in porcine ovarian granulosa cells (GCs) which are essential for follicle fate and sow fertility. In this study, the expression profiles of 12 widely-used RGs (GAPDH, RPLP0, ACTB, TUBA1B, EIF3K, PPIA, ATP5F1, B2M, HPRT1, UBC, RPS3, and EEF1A1) in porcine GCs during follicular development and under different abiotic stresses were systematically investigated. Expression stability of the candidate RGs were comprehensively accessed by five statistical algorithms including ΔCt, NormFinder, BestKeeper, geNorm, and RefFinder, indicating that RPS3 and PPIA are the optimal RGs during follicular development, EEF1A1 and RPLP0 are most stable under oxidative stress and inflammation, while ATP5F1, B2M, and RPS3 have higher stability under starvation and heat stress. Notably, the most commonly used RGs (ACTB, GAPDH, and TUBA1B) exhibited low stability in GCs. Reliability of stable RGs was verified by RT-qPCR and showed that selection of the stable RGs significantly improved the detection accuracy of qPCR, which confirms once again that the stability of RGs should not be taken for granted. Our findings identified optimal RG sets in porcine GCs under different conditions, which is helpful in future studies to accurately identify the key regulators and their expression patterns during follicular development in sows.

miR-423 sponged by lncRNA NORHA inhibits granulosa cell apoptosis.

BACKGROUND: Atresia and degeneration, a follicular developmental fate that reduces female fertility and is triggered by granulosa cell (GC) apoptosis, have been induced by dozens of miRNAs. Here, we report a miRNA, miR-423, that inhibits the initiation of follicular atresia (FA), and early apoptosis of GCs. RESULTS: We showed that miR-423 was down-regulated during sow FA, and its levels in follicles were negatively correlated with the GC density and the P4/E2 ratio in the follicular fluid in vivo. The in vitro gain-of-function experiments revealed that miR-423 suppresses cell apoptosis, especially early apoptosis in GCs. Mechanically speaking, the miR-423 targets and interacts with the 3'-UTR of the porcine SMAD7 gene, which encodes an apoptosis-inducing factor in GCs, and represses its expression and pro-apoptotic function. Interestingly, FA and the GC apoptosis-related lncRNA NORHA was demonstrated as a ceRNA of miR-423. Additionally, we showed that a single base deletion/insertion in the miR-423 promoter is significantly associated with the number of stillbirths (NSB) trait of sows. CONCLUSION: These results demonstrate that miR-423 is a small molecule for inhibiting FA initiation and GC early apoptosis, suggesting that treating with miR-423 may be a novel approach for inhibiting FA initiation and improving female fertility.

Upregulation of CELSR1 expression promotes ovarian cancer cell proliferation, migration, and invasion.

Cadherin epidermal growth factor and laminin-G seven-pass G-type receptor 1 (CELSR1) is a planar cell polarity protein involved in the transmission of directional cues to align either individual cells within an epithelial sheet or multicellular clusters. CELSR1 has been suggested to play a role in glioma, breast cancer, and chronic lymphocytic leukemia development; however, whether it has a role in the pathogenesis of ovarian cancer remains unknown. The aim of this study was to determine the role of CELSR1 in ovarian cancer and elucidate its underlying molecular mechanisms. By analyzing gene expression data downloaded from the Cancer Genome Atlas database, we found that CELSR1 expression was upregulated in ovarian cancer tissues compared to that in normal ovarian tissues. High CELSR1 expression levels were associated with poor prognosis in patients with ovarian cancer. Cell proliferation, scratch, and transwell assays revealed that CELSR1 promoted the proliferation, migration, and invasion of ovarian cancer cells in vitro. In addition, transcriptome sequencing analysis revealed that CELSR1 knockdown in T29H cells resulted in the dysregulation of the expression of 1320 genes. Further analysis revealed that genes involved in proliferation- and migration-associated signaling pathways were regulated by CELSR1. Our study demonstrates that CELSR1 is highly expressed in ovarian cancer cells and regulates their proliferation and migration, suggesting its potential as a diagnostic marker and therapeutic target.

The role of non-canonical Hippo pathway in regulating immune homeostasis.

The Hippo pathway is a crucial signaling pathway that is highly conserved throughout evolution for the regulation of organ size and maintenance of tissue homeostasis. Initial studies have primarily focused on the canonical Hippo pathway, which governs organ development, tissue regeneration, and tumorigenesis. In recent years, extensive research has revealed that the non-canonical Hippo pathway, centered around Mst1/2 as its core molecule, plays a pivotal role in immune response and function by synergistically interacting with other signal transduction pathways. Consequently, the non-canonical Hippo pathway assumes significant importance in maintaining immune system homeostasis. This review concentrates on the research progress of the non-canonical Hippo pathway in regulating innate immune cell anti-infection responses, maintaining redox homeostasis, responding to microenvironmental stiffness, and T-cell differentiation.

Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339.

BACKGROUND: Functioning as a competing endogenous RNA (ceRNA) is the main action mechanism of most cytoplasmic lncRNAs. However, it is not known whether this mechanism of action also exists in the nucleus. RESULTS: We identified four nuclear lncRNAs that are presented in granulosa cells (GCs) and were differentially expressed during sow follicular atresia. Notably, similar to cytoplasmic lncRNAs, these nuclear lncRNAs also sponge miRNAs in the nucleus of GCs through direct interactions. Furthermore, NORSF (non-coding RNA involved in sow fertility), one of the nuclear lncRNA acts as a ceRNA of miR-339. Thereby, it relieves the regulatory effect of miR-339 on CYP19A1 encoding P450arom, a rate-limiting enzyme for E2 synthesis in GCs. Interestingly, miR-339 acts as a saRNA that activates CYP19A1 transcription and enhances E2 release by GCs through altering histone modifications in the promoter by directly binding to the CYP19A1 promoter. Functionally, NORSF inhibited E2 release by GCs via the miR-339 and CYP19A1 axis. CONCLUSIONS: Our findings highlight an unappreciated mechanism of nuclear lncRNAs and show it acts as a ceRNA, which may be a common lncRNA function in the cytoplasm and nucleus. We also identified a potential endogenous saRNA for improving female fertility and treating female infertility.

Feeding Spodoptera exigua larvae with gut-derived Escherichia sp. increases larval juvenile hormone levels inhibiting cannibalism.

Feed quality influences insect cannibalistic behavior and gut microbial communities. In the present study, Spodoptera exigua larvae were fed six different artificial diets, and one of these diets (Diet 3) delayed larval cannibalistic behavior and reduced the cannibalism ratio after ingestion. Diet 3-fed larvae had the highest gut bacterial load (1.396 ± 0.556 × 1014 bacteria/mg gut), whereas Diet 2-fed larvae had the lowest gut bacterial load (3.076 ± 1.368 × 1012 bacteria/mg gut). The gut bacterial composition and diversity of different diet-fed S. exigua larvae varied according to the 16S rRNA gene sequence analysis. Enterobacteriaceae was specific to the Diet 3-fed larval gut. Fifteen culturable bacterial isolates were obtained from the midgut of Diet 3-fed larvae. Of these, ten belonged to Escherichia sp. After administration with Diet 1- or 2-fed S. exigua larvae, two bacterial isolates (SePC-12 and -37) delayed cannibalistic behavior in both tested larval groups. Diet 2-fed larvae had the lowest Juvenile hormone (JH) concentration and were more aggressive against intraspecific predation. However, SePC-12 loading increased the JH hormone levels in Diet 2-fed larvae and inhibited their cannibalism. Bacteria in the larval midgut are involved in the stabilization of JH levels, thereby regulating host larval cannibalistic behavior.

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.

Intrinsic Stress-strain in Barium Titanate Piezocatalysts Enabling Lithium-Oxygen Batteries with Low Overpotential and Long Life.

Rechargeable lithium-oxygen (Li-O2 ) batteries with high theoretical energy density are considered as promising candidates for portable electronic devices and electric vehicles, whereas their commercial application is hindered due to poor cyclic stability caused by the sluggish kinetics and cathode passivation. Herein, the intrinsic stress originated from the growth and decomposition of the discharge product (lithium peroxide, Li2 O2 ) is employed as a microscopic pressure resource to induce the built-in electric field, further improving the reaction kinetics and interfacial Lithium ion (Li+ ) transport during cycling. Piezopotential caused by the intrinsic stress-strain of solid Li2 O2 is capable of providing the driving force for the separation and transport of carriers, enhancing the Li+ transfer, and thus improving the redox reaction kinetics of Li-O2 batteries. Combined with a variety of in situ characterizations, the catalytic mechanism of barium titanate (BTO), a typical piezoelectric material, was systematically investigated, and the effect of stress-strain transformation on the electrochemical reaction kinetics and Li+ interface transport for the Li-O2 batteries is clearly established. The findings provide deep insight into the surface coupling strategy between intrinsic stress and electric fields to regulate the electrochemical reaction kinetics behavior and enhance the interfacial Li+ transport for battery system.

Permeameter and solenoid measurements of Epstein strips of electrical steels.

The dc and ac flux density vs magnetic field B(H) loops of Epstein electrical strips are measured in an IEC type-A permeameter with a high-quality electrical strip wound double yokes of inside length l0 = 0.2 m and inside height h0 = 0.1 m and in a long solenoid. The relevant demagnetizing and eddy-current effects are analyzed, modeled, and discussed. It is concluded that demagnetizing corrected solenoid measurement developed for determining dc B(H) loops of the material cannot be used for the ac case, owing to complicated eddy-current demagnetizing effects. Permeameter-measured ac B(H) loops with H detected by a flat H-coil of length less than l0/2 touching the strip's middle surface may be considered representative of the actual material because H is very uniform along the strip within 3l0/4. Strips with ac B(H) loops thus determined should be used to calibrate the effective magnetic path length lm of Epstein measurements, where a very nonuniform field is applied to the strips.

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.