Influence of repeated mastitis on the milk production and metabolic status in the subsequent lactation period of dairy cattle.

Recurrent mastitis poses a common challenge on dairy farms. While the impact of repeated mastitis within the same lactation has been investigated, the difference from one lactation to the next, particularly concerning the change of milk and blood metabolites, remains unclear. This study aimed to examine the difference in milk yield, milk composition, and metabolic status in the subsequent lactation between healthy and repeated mastitis in the previous lactation. The study population comprised 50 cows chosen from 400 cows, with 25 having no history of mastitis and 25 experiencing mastitis more than three times during the last lactation. Following dry-off and calving, all cows initiated a new lactation, during which no mastitis was diagnosed until the sample collection period. In the group exposed to repeated mastitis, a significant decrease in milk fat levels was observed in the subsequent lactation, while no change was observed in milk somatic cell count (SCC). Milk collected from cows that had experienced repeated mastitis in the previous lactation exhibited significant increases in the levels of free amino acids, namely valine, proline, and alanine. However, no difference in plasma levels of these amino acids was noted. These results indicate that individuals exposed to repeated mastitis have persistent milk quality changes even after dry-off. Biomarker analysis suggested that the milk valine and proline showed a moderate biomarker potential on Kappa coefficients to characterize cows that have experienced repeated mastitis. Furthermore, the results of biomarker combinations for valine and proline provided the highest specificity (100 %), positive likelihood ratio (infinity), and substantial biomarker potential on kappa coefficients (0.68). These findings significantly enhance our understanding of the pathobiology and etiology of recurrent mastitis and provide a biomarker to characterize cows that have experienced repeated mastitis in the past.

Zinc hybrid polyester barrier membrane accelerates guided tissue regeneration.

Barrier membranes play a pivotal role in the success of guided periodontal tissue regeneration. The biodegradable barriers predominantly used in clinical practice often lack sufficient barrier strength, antibacterial properties, and bioactivity, frequently leading to suboptimal regeneration outcomes. Although with advantages in mechanical strength, biodegradability and plasticity, bioinert aliphatic polyesters as barrier materials are usually polymerized via toxic catalysts, hard to be functionalized and lack of antibacterial properties. To address these challenges, we propose a new concept that controlled release of bioactive substance on the whole degradation course can give a bioinert aliphatic polyester bioactivity. Thus, a Zn-based catalytic system for polycondensation of dicarboxylic acids and diols is created to prepare zinc covalent hybrid polyester (PBS/ZnO). The atomically-dispersed Zn2+ ions entering main chain of polyester molecules endow PBS/ZnO barrier with antibacterial properties, barrier strength, excellent biocompatibility and histocompatibility. Further studies reveal that relying on long-term controlled release of Zn2+ ions, the PBS/ZnO membrane greatly expedites osteogenetic effect in guided tissue regeneration (GTR) by enhancing the mitochondrial function of macrophages to induce M2 polarization. These findings show a novel preparation strategy of bioactive polyester biomaterials based on long term controlled release of bioactive substance that integrates catalysis, material structures and function customization.

Evolutionary characteristics of global offshore carbon emissions network and responsibility allocation of emissions reduction.

Offshore carbon emissions from the international shipping trade are significant contributors to climate change. Based on the complex shipping trade networks, offshore carbon emissions are correlated rather than independent, and allocating responsibility for reducing emissions does not depend solely on the amount but on linkages. We use the global container shipping data covering more than 98% of routes from 2015 to 2020 to calculate the offshore carbon emissions from shipping. Subsequently, we construct an offshore carbon emissions network based on the shipping routes and emissions to identify the evolutionary tendency of network and clarify emissions reduction responsibilities by considering equity and efficiency. We discover that global offshore carbon emissions present a complicated network structure dominated by developed countries and large economies. Countries on the same continent or within the same economic organizations have closer and more frequent carbon correlations. Greater responsibilities should be allocated to countries who are at the center of the network.

Influence of Dentist-Related Risk Factors on Implant Survival Provided by Dentists Without Structured Training: Results of a Retrospective Cross-Sectional Study.

PURPOSE: To evaluate the cumulative survival rate (CSR) of implants placed by Chinese dentists who lacked structured training and to identify the dentist-related risk factors associated with implant failure. MATERIALS AND METHODS: Data from 2,036 patients who underwent implant-supported restoration at a university-affiliated stomatology hospital were collected. CSR was regarded as the dependent variable. Patient-related characteristics (age, sex, insertion site, and surgical complexity) and dentist-related factors (experience, number of implant brands used, education level, sex, and specialty) were collected as independent variables. The chi-square test was used to identify dentist-related factors for implant failure after addressing patient-related potential confounders using propensity score matching (PSM). Dentist- and patient-related risk factors were further analyzed using multivariable logistic regression within the subgroups. RESULTS: The CSRs were 98.48% for patients (with single or multiple implants) and 98.86% for implants after 48 to 60 months of observation. Dentists with < 5 years of experience and specialists in implant dentistry were significantly associated with implant failure after addressing potential patient-related confounders. Within the group of dentists with < 5 years of experience, complicated cases were the major risk factor. For the group of specialists in implant dentistry, < 5 years of experience and male patient were the major risk factors. CONCLUSION: New dentists (< 5 years of experience) and specialists in implant dentistry are considered to be dentist-related risk factors for implant failure. This confirms that a learning curve exists for new specialists to reach the level of proficiency and expertise. Int J Oral Maxillofac Implants 2023;38:553-561. doi: 10.11607/jomi.9969.

Efficacy of Scalp Acupuncture with the Long-Stay Method on Motor Dysfunction in Patients with Acute Ischemic Stroke: A Randomized Controlled Trial.

Background: In China, acupuncture has been widely used in treating cerebrovascular diseases since time immemorial. Scalp acupuncture using the long-stay method is a traditional acupuncture treatment. However, previous studies have concluded that the clinical efficacy of scalp acupuncture for the treatment of stroke remains uncertain. In addition, no randomized controlled trials have been conducted on scalp acupuncture using the long-stay method. This study aimed to evaluate the efficacy and safety of the long-stay method of scalp acupuncture for limb movement dysfunction in patients after acute ischemic stroke (AIS). Methods: Seventy-two patients with acute strokes were randomly divided into treatment and control groups. The control group received conventional acupuncture with a half-hour needle stay each time, whereas the treatment group underwent scalp needling using a long retention method, with each retention of needles lasting 24 hours. Both groups received acupuncture treatment for 2 weeks and were followed up for 6 months. Cerebrovascular reserve (CVR), breath-holding index (BHI), pulsatility index (PI), Fugl-Meyer, and Barthel index (BI) were assessed at baseline, week 1, week 2, and during follow-up. Results: Compared with the baseline, both groups showed a significant improvement in CVR, Fugl-Meyer, BI, PI, and BHI (P < 0.05). Compared with the control group, the treatment group showed more significant improvements in Fugl-Meyer scores, BI, CVR, PI, and BHI (P < 0.05). Correlation analysis showed that Fugl-Meyer and BI scores increased significantly with CVR recovery over the course of treatment. Conclusion: Scalp acupuncture with the long-stay method can improve neurological deficits and the ability to perform daily activities among AIS patients, which may be related to the improvement of CVR function in patients.

Click-based injectable bioactive PEG-hydrogels guide rapid craniomaxillofacial bone regeneration by the spatiotemporal delivery of rhBMP-2.

Craniomaxillofacial bone defects result in physical and psychological dual injuries making the promotion or acceleration of bone regeneration imperative. In this work, a fully biodegradable hydrogel is facilely prepared via thiol-ene "click" reactions under human physiological conditions using multifunctional poly(ethylene glycol) (PEG) derivatives as precursors. This hydrogel shows excellent biological compatibility, enough mechanical strength, a low swelling rate and an appropriate degradation rate. Rat bone marrow mesenchymal stem cells (rBMSCs) can survive and proliferate on/in the PEG hydrogel and differentiate into osteogenic cells. The PEG hydrogel can also effectively load rhBMP-2 through the above "click" reaction. Under the physical barrier of the chemically crosslinked hydrogel network, the spatiotemporal release of rhBMP-2 effectively promotes the proliferation and osteogenic differentiation of rBMSCs at a loading concentration of 1 µg ml-1. Finally, based on a rat calvarial critical-size defect model, the rhBMP-2 immobilized hydrogel loaded with rBMSCs basically accomplishes the repair and regeneration within 4 weeks featured by remarkably enhanced osteogenesis and angiogenesis. The click-based injectable bioactive PEG hydrogel developed in the present study is a new type of bone substitute with great expectations in future clinical applications.

Kunling Wan improves oocyte quality by regulating the PKC/Keap1/Nrf2 pathway to inhibit oxidative damage caused by repeated controlled ovarian hyperstimulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Kunling Wan (KW) is a traditional Chinese medicine that is principally used for kidney deficiency, qi stagnation, and blood stasis, which are basic syndromes of infertility in China. KW can improve ovarian follicular development, ovarian function, and endometrial receptivity, which lead to improving pregnancy outcomes. Repeated controlled ovarian hyperstimulation (COH) reduces oocyte quality and results in a lower pregnancy rate. Whether KW has the potential to improve oocyte quality reduced by repeated COH has yet to be determined. AIMS OF THE STUDY: The aim of this study wwas to evaluate the effect of KW on oocyte quality after damage due to repeated COH, and to investigate the mechanism(s) underlying the antioxidative protection of oocytes by mitochondria. MATERIALS AND METHODS: Female Kunming mice were randomly divided into four groups: normal group, model (repeated COH) group, KW group, and N-acetylcysteine (NAC) group. We observed the morphology and quality of mitochondria, level of reactive oxygen species (ROS), and antioxidant enzymes activity of each group. Oocytes were treated with H2O2 and KW-containing serum, and we determined the antioxidant effects of KW on H2O2-treated oocytes and the mechanism involved in the regulation of Nrf2 in reducing oxidative damage. RESULTS: Our results revealed that repeated COH caused oxidative damage and impaired oocyte mitochondrial function and structure, resulting in poor oocyte quality. KW pretreatment reduced oxidative damage by inhibiting ROS production and improving mitochondrial structure and function, thereby enhancing overall oocyte quality. In response to H2O2, KW activated the PKC/Keap1/Nrf2-signaling pathway and promoted the translocation of Nrf2 from the cytoplasm to the nucleus, which activated the expression of SOD and GSH-Px, and removed the excess ROS that caused the initial mitochondrial damage. CONCLUSIONS: KW improved oocyte quality perturbed by repeated COH via reducing oxidative effects and improving mitochondrial function. The mechanism may be related to regulation of the PKC/Keap1/Nrf2 pathway in removing excess ROS.

Erratum: GCN5 participates in KLF4-VEGFA feedback to promote endometrial angiogenesis.

[This corrects the article DOI: 10.1016/j.isci.2022.104509.].

Morroniside Protects Human Granulosa Cells against H2O2-Induced Oxidative Damage by Regulating the Nrf2 and MAPK Signaling Pathways.

Morroniside is the main ingredient of Cornus officinalis and has a variety of biological activities including antioxidative effects. Ovarian granulosa cells (GCs) are responsible for regulating the development and atresia of follicles, which are susceptible to oxidative stress. In this study, we determined whether morroniside can inhibit the oxidative stress of GCs induced by hydrogen peroxide (H2O2), leading to improved oocyte quality. The oxidative damage and apoptosis of ovarian GCs cultured in vitro were induced by the addition of H2O2. After pretreatment with morroniside, the levels of ROS, MDA, and 8-OHdG in ovarian GCs were significantly decreased. Morroniside significantly upregulated p-Nrf2 and promoted the nuclear translocation of Nrf2, which transcriptionally activated antioxidant SOD and NQO1. In addition, morroniside significantly regulated the levels of apoptosis-related proteins Bax, Bcl-2, cleaved caspase-9, and cleaved caspase-3 via the p38 and JNK pathways. These results suggest that morroniside can reduce the oxidative damage and apoptosis of ovarian GCs induced by H2O2.

Difficult and complicated oral ulceration: an expert consensus guideline for diagnosis.

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.

GCN5 participates in KLF4-VEGFA feedback to promote endometrial angiogenesis.

Endometrial angiogenesis is necessary for good endometrial receptivity. Krüppel-like factor 4 (KLF4) is a transcription factor that is essential for regulating angiogenesis. Here we found that vascular endothelial growth factor A (VEGFA) can form a positive feedback loop with KLF4 to promote the proliferation and migration of human endometrial microvascular endothelial cells (HEMECs) and inhibit cell apoptosis. General control non-derepressible 5 (GCN5) is also time-dependent on VEGFA and participates in the KLF4-VEGFA loop. In addition, we found that GCN5 is a succinyltransferase that modulates the succinylation of histones and nonhistones. GCN5 interacts with KLF4 and is recruited to the KLF4-binding site of the VEGFA promoter to succinylate H3K79, which initiates gene transcription epigenetically. For nonhistones, GCN5 succinylates KLF4 that is activated by ERK signaling in HEMECs treated with VEGFA to increase its transcription activity. These results demonstrate KLF4-VEGFA positive feedback loop is regulated by epigenetics, which contributes to endometrial angiogenesis.

N-Acetylcysteine improves oocyte quality through modulating the Nrf2 signaling pathway to ameliorate oxidative stress caused by repeated controlled ovarian hyperstimulation.

CONTEXT: N -acetyl-cysteine (NAC) is a potent antioxidant that can be used for many gynecological diseases such as polycystic ovary syndrome and endometriosis. Controlled ovarian hyperstimulation (COH) is a critical step in infertility treatment. Our previous clinical studies have shown that repeated COH led to oxidative stress in follicle fluid and ovarian granulosa cells. AIMS: In this study, we investigated whether NAC could inhibit oxidative stress in mice caused by repeated COH and improve the mitochondrial function of oocytes. METHODS: Female Institute of Cancer Research (ICR) mice were randomly assigned into three groups: normal group, model (repeated COH) group, NAC group. We examined the morphology, number and quality of mitochondria. The mechanism of regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) by NAC to ameliorate oxidative stress was also investigated. KEY RESULTS: Repeated COH caused oxidative damage in ovaries and oocytes and decreased oocyte quality, while NAC prevented oxidative damage and increased oocyte mitochondrial function. In in vitro experiments, it was verified that NAC can promote the nuclear translocation of Nrf2, which transcriptionally activates the expression of superoxide dismutase and glutathione peroxidase, which removed excessive reactive oxygen species that causes mitochondria damage. CONCLUSIONS: The results suggest that NAC raises mitochondrial function in oocytes and improves oocyte quality through decreasing oxidative stress in mice with repeated COH. The underlying mechanism is related to the regulation of the Nrf2 signaling pathway. IMPLICATION: This study provides a meaningful foundation for the future clinical application of NAC during repeated COH.

Effects of multicycle gonadotropin-releasing hormone antagonist protocols on oxidative stress of follicular fluid and ovarian granulosa cells.

The effect of repeated multicycle gonadotropin-releasing hormone antagonist (GnRH-ant) protocols on oxidative stress (OS) in follicular fluid (FF) and ovarian granulosa cells (GCs) remains unclear. This study investigated the effects of repeated multicycle GnRH-ant protocols on OS markers of FF and ovarian GCs. A total of 145 patients were enrolled and divided into four groups: 1 cycle group (n = 42), 2 cycles group (n = 37), 3 cycles group (n = 45), and 4-5 cycles group (n = 21). The FF and ovarian GCs of the patients were collected on the day of last oocyte retrieval and the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were tested by ELISA. The results showed that the serum estradiol levels on hCG injection day in the 3 and 4-5 cycles were significantly (P < 0.05) lower than in the 1 and 2 cycles. The number of retrieved oocytes (12.1 ± 3.3 in cycle 1, 11.7 ± 3.1 in cycle 2, 10.4 ± 2.4 in cycle 3, and 9.4 ± 2.4 in cycles 4-5), embryos with two pronuclei (7.6 ± 3.0 in cycle 1, 7.0 ± 2.5 in cycle 2, 6.2 ± 2.6 in cycle 3, and 5.5 ± 2.1 in cycles 4-5), and the rates of high-quality embryos (52.2% in cycle 1, 47.9% in cycle 2, 38.6% in cycle 3, and 36.5% in cycles 4-5), implantation (35.4% in cycle 1, 32.4% in cycle 2, 23.8% in cycle 3, and 22.9% in cycles 4-5) and clinical pregnancy (50.0% in cycle 1, 43.2% in cycle 2, 33.3% in cycle 3, and 23.8% in cycles 4-5) in cycles 3 and 4-5 were significantly (P < 0.05) lower than those in cycles 1 and 2. Compared with 1 and 2 cycles, the 8-OHdG and SOD were significantly increased in the 3-5 cycles, while the CAT and GSH-Px levels were significantly decreased. Together, this study reveals repeated COS with the use of GnRH-ant protocols results in OS and changes the follicle microenvironment of FF and GCs, possibly leading to poor IVF outcomes in patients with 3-5 cycles of COS.

Osteogenic effects of antihypertensive drug benidipine on mouse MC3T3-E1 cells in vitro.

Hypertension is a prevalent systemic disease in the elderly, who can suffer from several pathological skeletal conditions simultaneously, including osteoporosis. Benidipine (BD), which is widely used to treat hypertension, has been proved to have a beneficial effect on bone metabolism. In order to confirm the osteogenic effects of BD, we investigated its osteogenic function using mouse MC3T3-E1 preosteoblast cells in vitro. The proliferative ability of MC3T3-E1 cells was significantly associated with the concentration of BD, as measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell cycle assay. With BD treatment, the osteogenic differentiation and maturation of MC3T3-E1 cells were increased, as established by the alkaline phosphatase (ALP) activity test, matrix mineralized nodules formation, osteogenic genetic test, and protein expression analyses. Moreover, our data showed that the BMP2/Smad pathway could be the partial mechanism for the promotion of osteogenesis by BD, while BD might suppress the possible function of osteoclasts through the OPG/RANKL/RANK (receptor activator of nuclear factor-κB (NF-κB)) pathway. The hypothesis that BD bears a considerable potential in further research on its dual therapeutic effect on hypertensive patients with poor skeletal conditions was proved within the limitations of the present study.

Estrogen Regulates Endoplasmic Reticulum Stress-Mediated Apoptosis by ERK-p65 Pathway to Promote Endometrial Angiogenesis.

Estrogen (17ß-oestradiol, E2) plays an essential role in endometrial receptivity and has been shown to stimulate angiogenesis via E2-ERα (estrogen receptor)-mediated upregulation of VEGF transcription. In this study, we have tried to decipher the mechanism of E2-promoting angiogenesis. We pre-incubated human endometrial microvascular endothelial cells (HEMECs) with E2 and performed western blotting, qRT-PCR, and cellular immunofluorescence experiments. We observed that E2 treatment of HEMECs increased ERα expression and reduced the expression of GRP78, which led to reduction of Caspase 3 expression by the CHOP pathway. In addition, E2 not only activated ERK signaling pathway but also inhibited p65 phosphorylation along with its translocation from nucleus to the cytoplasm, and subsequently inhibiting GRP78 expression, which led to inhibition of cell apoptosis. Together, these findings highlight the novel mechanism underlying E2-mediated improvement in endometrial angiogenesis through the ERK-p65 signaling pathway.

Preparation and biological evaluations of a collagen-like hierarchical Ti surface with superior osteogenic capabilities.

The construction of multiscale Ti surfaces of high osteogenic ability has always attracted significant attention in the fields of oral implantology and implantable biomaterials. However, to date, the absence of a solid understanding of the correlation between the multiscale surface structure and the biological properties is the main obstacle in the development of these multiscale implants. In this study, a series of novel multiscale Ti surfaces were prepared via a three-step subtractive method. Moreover, based on the grayscale analysis of SEM images, we developed multiscale surface topography analysis methods. The typical topography characteristics at each scale of a multiscale complex surface can be analyzed according to the corresponding magnified SEM images. Thus, the evolution rule of the surface topography from a simple surface to multiscale complex surfaces can be mathematically described. Based on this, the correlation between multiscale surface structures and the corresponding biological properties was established. For the multiscale surface of superior osteogenic capacity, strict inherent regularity was found among the structures at multiple scales (i.e., multiscale order), that is, there was a balance between the construction of the 3D collagen-like network nanostructure and the preservation of the typical topographical features of the pre-existing macro- and micro-structures of the classic micro-roughened surface. Moreover, it was further found that the multiscale-ordered hierarchical Ti surface structure could modulate ROS production and enhance macrophage M2 polarization to create an osteogenesis-favorable immuno-inflammatory microenvironment and synergistically exhibit superior biological capability. Consequently, an optimized collagen-like hierarchical surface with superior osteogenic abilities was achieved.

Toward Efficient Action Recognition: Principal Backpropagation for Training Two-Stream Networks.

In this paper, we propose the novel principal backpropagation networks (PBNets) to revisit the backpropagation algorithms commonly used in training two-stream networks for video action recognition. We content that existing approaches always take all the frames/snippets for the backpropagation not optimal for video recognition since the desired actions only occur in a short period within a video. To remedy these drawbacks, we design a watch-and-choose mechanism. In particular, the watching stage exploits a dense snippet-wise temporal pooling strategy to discover the global characteristic for each input video, while the choosing phase only backpropagates a small number of representative snippets that are selected with two novel strategies, i.e., Max-rule and KL-rule. We prove that with the proposed selection strategies, performing the backpropagation on the selected subset is capable of decreasing the loss of the whole snippets as well. The proposed PBNets are evaluated on two standard video action recognition benchmarks UCF101 and HMDB51, where it surpasses the state of the arts consistently, but requiring less memory and computation to achieve high performance.

Transcriptomic Analysis of Flower Bud Differentiation in Magnolia sinostellata.

Magnolias are widely cultivated for their beautiful flowers, but despite their popularity, the molecular mechanisms regulating flower bud differentiation have not been elucidated. Here, we used paraffin sections and RNA-seq to study the process of flower bud differentiation in Magnolia sinostellata. Flower bud development occurred between 28 April and 30 May 2017 and was divided into five stages: undifferentiated, early flower bud differentiation, petal primordium differentiation, stamen primordium differentiation, and pistil primordium differentiation. A total of 52,441 expressed genes were identified, of which 11,592 were significantly differentially expressed in the five bud development stages. Of these, 82 genes were involved in the flowering. In addition, MADS-box and AP2 family genes play critical roles in the formation of flower organs and 20 differentially expressed genes associated with flower bud differentiation were identified in M. sinostellata. A qRT-PCR analysis verified that the MADS-box and AP2 family genes were expressed at high levels during flower bud differentiation. Consequently, this study provides a theoretical basis for the genetic regulation of flowering in M. sinostellata, which lays a foundation for further research into flowering genes and may facilitate the development of new cultivars.

In vitro influence of selenium on the proliferation of and steroidogenesis in goat luteinized granulosa cells.

In this study, we investigated the effects of Selenium (Se) on the proliferation of and steroidogenesis in goat luteinized granulosa cells (LGCs) and elucidated the mechanisms underlying these effects. Our results showed that proliferating cell nuclear antigen (PCNA), Akt, and phosphoinositide 3-kinase (PI3K) were expressed mainly in ovarian oocytes and granulosa cells (GCs). We observed that 5 ng/mL Se significantly stimulated LGC proliferation, which could be attributed to increases in PCNA, cyclin-dependent kinase 1 (CDK1), phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK; Thr172), and phosphorylated Akt (p-Akt; Ser473) and decreases in p21 (P < 0.05). Se treatment also significantly increased estradiol (E2) production, which could be, at least partially, due to increased levels of 3ß-hydroxysteroid dehydrogenase(3ß-HSD), steroidogenic acute regulatory protein (StAR), p-Akt (Ser473), and cyclic adenosine monophosphate (cAMP) (P < 0.05); however, follicle-stimulating hormone (FSH) significantly enhanced the production of E2, progesterone (P4) and cAMP (P < 0.05). Moreover, Se treatment stimulated proliferation and the synthesis of E2 and cAMP in the presence of FSH (P < 0.05). Additionally, the expression of antioxidant-related genes [glutathione peroxidase (GSH-Px) and superoxide dismutase 2 (SOD2)] and the activity of GSH-Px and SOD were progressively elevated by Se treatment (P < 0.05). These data suggested that Se plays an important role in the proliferation of and steroidogenesis in LGC by activating the PI3K/Akt and AMPK pathways, thereby increasing the expression of its downstream cell-cycle- and steroid-synthesis-related genes, as well as regulating cellular oxidative stress.