Centrosymmetry-Breaking Morphotropic Phase Boundary: A Pathway to Highly Sensitive and Strong Pressure-Responsive Nonlinear Optical Switches.

The quest for high-performance piezoelectric materials has been synonymous with the pursuit of the morphotropic phase boundary (MPB), yet the full potential of MPBs remains largely untapped outside of the realm of ferroelectrics. In this study, we reveal a new class of MPB by creating continuous molecular-based solid solutions between centro- and noncentrosymmetric compounds, exemplified by (tert-butylammonium)1-x(tert-amylammonium)xFeCl4 (0 ≤ x ≤ 1), where the MPB is formed due to disorder of molecular cations. Near the MPB, we discovered an exceptionally sensitive nonlinear optical material in the centrosymmetric phase, capable of activation at pressures as low as 0.12-0.27 GPa, and producing tunable second-harmonic generation (SHG) signals from zero to 18.8 times that of KH2PO4 (KDP). Meanwhile, synchrotron diffraction experiments have unveiled a third competing phase (P212121) appearing at low pressure, forming a triple-phase point near the MPB, thereby providing insight into the mechanism underpinning the nonlinear optical (NLO) switch behavior. These findings highlight the opportunity to harness exceptional physical properties in symmetry-breaking solid solution systems by strategically designing novel MPBs.

LncRNA SNHG12 promotes cell proliferation and inhibits apoptosis of granulosa cells in polycystic ovarian syndrome by sponging miR-129 and miR-125b.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is the most common endocrine disease in women of childbearing age which is often associated with abnormal proliferation or apoptosis of granulosa cells (GCs). Studies proved that long non-coding RNA SNHG12 (lncRNA SNHG12) is significantly increased in ovarian cancer and cervical cancer patients and cells. The inhibition of lncRNA SNHG12 restrains the proliferation, migration, and invasion in tumor cells. OBJECTIVE: This study explores the role of lncRNA SNHG12 in the apoptosis of GCs in PCOS and the underlying regulated mechanism. METHODS: In this study, the injection of dehydroepiandrosterone (DHEA) successfully induced the PCOS model in SD rats. The human granulosa-like tumor cell line KGN was incubated with insulin to assess the effects of lncRNA SNHG12 on GC proliferation and apoptosis. RESULTS: Overexpression of lncRNA SNHG12 influenced the body weight, ovary weight, gonadal hormone, and pathological changes, restrained the expressions of microRNA (miR)-129 and miR-125b, while downregulation of lncRNA SNHG12 exerted the opposite effects in PCOS rats. After silencing lncRNA SNHG12 in cells, the cell viability and proliferation were lessened whereas apoptosis of cells was increased. A loss-of-functions test was implemented by co-transfecting miR-129 and miR-125b inhibitors into lncRNA SNHG12-knocking down cells to analyze the effects on cell viability and apoptosis. Next, the existence of binding sites of SNHG12 and miR-129/miR-125b was proved based on the pull-down assay. CONCLUSION: lncRNA SNHG12 might be a potential regulatory factor for the development of PCOS by sponging miR-129 and miR-125b in GCs.

Tailoring competitive adsorption sites of hydroxide ion to enhance urea oxidation-assisted hydrogen production.

Alloys with bimetallic electron modulation effect are promising catalysts for the electrooxidation of urea. However, the side reaction oxygen evolution reaction (OER) originating from the competitive adsorption of OH- and urea severely limited the urea oxidation reaction (UOR) activity on the alloy catalysts. This work successfully constructs the defect-rich NiCo alloy with lattice strain (PMo-NiCo/NF) by rapid pyrolysis and co-doping. By taking advantage of the compressive strain, the d-band center of NiCo is shifted downward, inhibiting OH- from adsorbing on the NiCo site and avoiding the detrimental OER. Meanwhile, the oxygenophilic P/Mo tailored specific adsorption sites to adsorb OH- preferentially, which further released the NiCo sites to ensure the enriched adsorption of urea, thus improving the UOR efficiency. As a result, PMo-NiCo/NF only requires 1.27 V and -57 mV to drive a current density of ±10 mA cm-2 for UOR and hydrogen evolution reaction (HER), respectively. With the guidance of this work, reactant competing adsorption sites could be tailored for effective electrocatalytic performance.

CPEB1 induces autophagy and promotes apoptosis in ovarian granulosa cells of polycystic ovary syndrome.

Inflammatory damage in ovarian granulosa cells (GCs) is a key mechanism in polycystic ovary syndrome (PCOS), cytoplasmic polyadenylation element binding protein-1 (CPEB1) is important in inflammatory regulation, however, its role in PCOS is unclear. We aim to research the mechanism of CPEB1 in ovarian GCs in PCOS using dehydroepiandrosterone (DHEA)-induced PCOS rat models and testosterone-incubated GC models. The pathophysiology in PCOS rats was analyzed. Quantitative-realtime-PCR, TUNEL, immunohistochemistry, and Western blot were applied for quantification. Additionally, cell counting kit-8, flow cytometry, immunofluorescence, Western blot, and Monodansylcadaverine staining were performed. We found that PCOS rat models exhibited a disrupted estrus cycle, elevated serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), increased LH/FSH ratio, and heightened ovarian index. Furthermore, reduced corpus luteum and increased follicular cysts were observed in ovarian tissue. In ovarian tissue, autophagy and apoptosis were activated and CPEB1 was overexpressed. In vitro, CPEB1 overexpression inhibited cell viability and sirtuin-1 (SIRT1), activated tumor necrosis factor-α, and interleukin-6 levels, as well as apoptosis and autophagy; however, CPEB1 knockdown had the opposite effect. In conclusion, overexpression of CPEB1 activated autophagy and apoptosis of ovarian GCs in PCOS.

OAS Deep Q-Learning-Based Fast and Smooth Control Method for Traffic Signal Transition in Urban Arterial Tidal Lanes.

To address traffic flow fluctuations caused by changes in traffic signal control schemes on tidal lanes and maintain smooth traffic operations, this paper proposes a method for controlling traffic signal transitions on tidal lanes. Firstly, the proposed method includes designing an intersection overlap phase scheme based on the traffic flow conflict matrix in the tidal lane scenario and a fast and smooth transition method for key intersections based on the flow ratio. The aim of the control is to equalize average queue lengths and minimize average vehicle delays for different flow directions at the intersection. This study also analyses various tidal lane scenarios based on the different opening states of the tidal lanes at related intersections. The transitions of phase offsets are emphasized after a comprehensive analysis of transition time and smoothing characteristics. In addition, this paper proposes a coordinated method for tidal lanes to optimize the phase offset at arterial intersections for smooth and rapid transitions. The method uses Deep Q-Learning, a reinforcement learning algorithm for optimal action selection (OSA), to develop an adaptive traffic signal transition control and enhance its efficiency. Finally, a simulation experiment using a traffic control interface is presented to validate the proposed approach. This study shows that this method leads to smoother and faster traffic signal transitions across different tidal lane scenarios compared to the conventional method. Implementing this solution can benefit intersection groups by reducing traffic delays, improving traffic efficiency, and decreasing air pollution caused by congestion.

Gut microbiota and its metabolic products in acute respiratory distress syndrome.

The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed.

Superstructured Optoionic Heterojunctions for Promoting Ion Pumping Inspired by Photoreceptor Cells.

Photoreceptor cells of vertebrates feature ultrastructural membranes interspersed with abundant photosensitive ion pumps to boost signal generation and realize high gain in dim light. In light of this, superstructured optoionic heterojunctions (SSOHs) with cation-selective nanochannels are developed for manipulating photo-driven ion pumping. A template-directed bottom-up strategy is adopted to sequentially assemble graphene oxide (GO) and PEDOT:PSS into heterogeneous membranes with sculptured superstructures, which feature programmable variation in membrane topography and contain a donor-acceptor interface capable of maintaining electron-hole separation upon photoillumination. Such elaborate design endows SSOHs with a much higher magnitude of photo-driven ion flux against a concentration gradient in contrast to conventional optoionic membranes with planar configuration. This can be ascribed to the buildup of an enhanced transmembrane potential owing to the effective separation of photogenerated carriers at the heterojunction interface and the increase of energy input from photoillumination due to a synergistic effect of reflection reduction, broad-angle absorption, and wide-waveband absorption. This work unlocks the significance of membrane topographies in photo-driven transmembrane transportation and proposes such a universal prototype that could be extended to other optoionic membranes to develop high-performance artificial ion pumps for energy conversion and sensing.

Agglomeration inhibition engineering of nickel-cobalt alloys by a sacrificial template for efficient urea electrolysis.

Designing efficient non-precious metal-based catalysts for urea oxidation reaction (UOR) is essential for achieving energy-saving hydrogen production and the treatment of wastewater containing ammonia. In this study, sodium dodecyl sulfate (SDS) is employed as a sacrificial template to synthesize NiCo alloy nanowires (NiCo(SDS)/CC), and the instinct formation mechanism is investigated. It is found that SDS can inhibit the Ostwald ripening during hydrothermal and calcination processes, which could release abundant active cobalt, thereby modulating the electronic structure to promote the catalytic reaction. Moreover, SDS as a sacrificial template can induce the deposition of metal atoms and increase the specific surface area of the catalyst, providing abundant active sites to accelerate the reaction kinetics. As expected, the NiCo(SDS)/CC exhibits good activity for both UOR and hydrogen evolution reactions (HER) and it requires only 1.31 V and -86 mV to obtain a current density of ±10 mA cm-2, respectively. This work provides a new strategy for reducing the agglomeration of transition metals to design high-performance composite catalysts for urea oxidation.

YAP represses intestinal inflammation through epigenetic silencing of JMJD3.

BACKGROUND: Epigenetics plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Some studies have reported that YAP is involved in inflammatory response and can regulate target genes through epigenetic modifications. JMJD3, a histone H3K27me3 demethylase, is associated with some inflammatory diseases. In this study, we investigated the role of YAP in the development of IBD and the underlying epigenetic mechanisms. RESULTS: YAP expression was significantly increased in both in vitro and in vivo colitis models as well as in patients with IBD. Epithelial-specific knockout of YAP aggravates disease progression in dextran sodium sulfate (DSS)-induced murine colitis. In the TNF-α-activated cellular inflammation model, YAP knockdown significantly increased JMJD3 expression. Coimmunoprecipitation experiments showed that YAP and EZH2 bind to each other, and chromatin immunoprecipitation-PCR (ChIP-PCR) assay indicated that silencing of YAP or EZH2 decreases H3K27me3 enrichment on the promoter of JMJD3. Finally, administration of the JMJD3 pharmacological inhibitor GSK-J4 alleviated the progression of DSS-induced murine colitis. CONCLUSION: Our findings elucidate an epigenetic mechanism by which YAP inhibits the inflammatory response in colitis through epigenetic silencing of JMJD3 by recruiting EZH2.

Prediction Model of Adverse Pregnancy Outcome in Pre-Eclampsia Based on Logistic Regression and Random Forest Algorithm.

Aim: To construct a prediction model for adverse pregnancy outcomes of preeclampsia (PE). Thus assisting clinicians to identify high-risk patients. Provide guidance for treatment intervention. Methods: A retrospective study was conducted on 319 PE patients admitted to the Huzhou Maternal and Child Health Hospital from April 2021 to December 2022, The patients were divided into an adverse group (93 cases) and a non-adverse group (226 cases) based on whether they had adverse pregnancy outcomes after admission. Collect clinical data from patients, using a single factor analysis to screen statistically significant indicators as input variables, the outcome of the analysis is dependent on the incidence of PE adverse pregnancy outcomes. Divide patients into training and testing sets in a 7:3 ratio, Logistic regression model and random forest model were constructed respectively. Evaluate the predictive performance of two statistical models. Results: Among the 319 PE patients included 93 had adverse pregnancy outcomes after admission. Among them, Age (OR: 1.702, 95%CI: 1.069~2.710), small gestational age (OR: 0.757,95%CI: 0.607~0.945), more clinical symptoms (OR: 3.618, 95%CI: 1.682~7.783), high 24 h proteinuria (OR: 2.532, 95%CI: 1.290~4.968), low PLT index (OR: 0.616, 95%CI: 0.419~0.906), high AST index (OR: 1.554, 95%CI: 1.012~2.387), high D-Dimer index (OR:1.966, 95%CI: 1.183~3.267) were the influencing factors of adverse pregnancy outcomes in PE patients. The test set found that the random forest model was superior to the Logistic regression model in predicting the risk of adverse pregnancy outcomes in PE patients. Conclusions: The random forest model has good stability in predicting the risk of adverse pregnancy outcomes in PE, and its prediction efficiency is better than the Logistic regression model.

High, Multiple, and Nonvolatile Polarizations in Organic-Inorganic Hybrid [(CH3)3(CH2CH2Cl)N]2InCl5·H2O for Memcapacitor.

Dielectrics with high, nonvolatile, and multiple polarizations are required for fabricating memcapacitors that enable high parallelism and low energy consumption in artificial neuromorphic computing systems as artificial synapses. Conventional ferroelectric materials based on displacive and order-disorder types generally have difficulty meeting these requirements due to their low polarization values (∼150 µC/cm2) and persistent electrical hysteresis loops. In this study, we report a novel organic-inorganic hybrid (CETM)2InCl5·H2O (CETM = (CH3)3(CH2CH2Cl)N) exhibiting an intriguing polarization vs electric field (charge vs voltage) "hysteresis loop" and a record-high nonvolatile polarization over 30 000 µC/cm2 at room temperature. The polarization is highly dependent on the period and amplitude of the ac voltage, showing multiple nonvolatile states. Electrochemical impedance spectroscopy, time-dependent current behavior, disparate resistor response in the dehydrated derivative (CETM)2InCl5, and the negative temperature dependence of ionic conductance support that the memcapacitor behavior of (CETM)2InCl5·H2O stems from irreversible long-range migration of protons. First-principles calculations further confirm this and clarify the microscale mechanism of anisotropic polarization response. Our findings may open up a new avenue for developing memcapacitors by harnessing the benefits of ion migration in organic-inorganic hybrids.

LIPUS combined with TFSC alleviates premature ovarian failure by promoting autophagy and inhibiting apoptosis.

OBJECTIVE: Premature ovarian failure (POF), also known as primary ovarian insufficiency, is a major cause of infertility in female worldwide. Excessive apoptosis and impaired autophagy in ovarian granulosa cells are the main pathological mechanisms of POF. The total flavonoids from semen cuscutae (TFSC) are often used in the treatment of gynecological endocrine disorders. In addition, low intensity pulsed ultrasound (LIPUS) is report as an effective method to improve ovarian function. This study aims to investigate the protective effect of POF by the combined use of TFSC and LIPUS. METHODS: POF rats model and granulosa cell model were successfully induced by tripterygium glycosides and cyclophosphamide, respectively. After that, model rats and cells received TFSC plus LIPUS administration. Then ovarian histomorphology, senescence, estrus cycle, and serum sex hormone levels were detected in rats. Ovarian tissue and granulosa cells autophagy and apoptosis levels were also assessed. RESULTS: Disturbed sex hormone levels, atrophied and senescent ovaries, and abnormal estrous cycle were found in POF rats. Meanwhile, cell autophagy was inhibited and cell apoptosis was activated in POF ovarian tissue and granulosa cells. However, TFSC combined with LIPUS improved these changes, and this combination treatment exhibited synergistic effects. The abnormal expression of the cell apoptosis-, autophagy-, and PI3K/AKT/mTOR signaling pathway-related proteins were also improved by combination treatment. CONCLUSION: The study found that the combination of TFSC and LIPUS can alleviate POF by modulating cell autophagy and apoptosis. The findings may provide a viable scientific basis for POF treatment.

The ameliorating effects of Guizhi Fuling Wan combined with rosiglitazone in a rat ovarian model of polycystic ovary syndrome by the PI3K/AKT/NF-κB and Nrf2/HO-1 pathways.

OBJECTIVE: GuizhiFulingWan (GFW) has been reported to be effective against polycystic ovary syndrome (PCOS) by possessing oxidative stress and inflammation which related to PI3K/AKT/NF-κB, Nrf2/HO-1 pathway. This study aims to probe the effects and mechanisms of GFW combined with rosiglitazone on PCOS via PI3K/AKT/NF-κB and Nrf2/HO-1 pathways. METHODS: A rat PCOS model established by dehydroepiandrosterone (DHEA) injection. The experiment was allocated to control, DHEA, GFW, rosiglitazone, GFW + rosiglitazone groups. Treatment for 30 days, we monitored weight and ovarian weight of rats. Fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), lipid metabolism indexes, estrous cycle and sex hormone-, inflammation-, oxidative stress-related factors were examined. Hematoxylin&eosin staining assessed ovarian tissue pathological changes. Western blot determined PI3K/AKT/NF-κB, Nrf2/HO-1 pathways-related markers. RESULTS: GFW and rosiglitazone treatment suppressed body weight and ovarian weight in PCOS rats. They also decreased FBG, FINS, HOMA-IR while inhibited total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and enhanced high-density lipoprotein (HDL). They ameliorated estrous cycle, ovarian histological changes and follicular development. They restrained testosterone (T), luteinizing hormone (LH) and accelerated estradiol (E2), progesterone (P), follicle stimulating hormone (FSH). They inhibited glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD) in serum while increased GSH-Px, SOD and decrease MDA in ovarian tissues. They reduced C-reactive protein, interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), IL-6, IL-1ß levels. GFW and rosiglitazone co-intervention regulated PI3K/AKT/NF-κB and Nrf2/HO-1 pathways in PCOS rats. CONCLUSION: GFW alleviated ovarian dysfunction in PCOS rats, which may be related to the PI3K/AKT/NF-κB, Nrf2/HO-1 pathways.

A hypernetwork-based urn model for explaining collective dynamics.

The topological characterization of complex systems has significantly contributed to our understanding of the principles of collective dynamics. However, the representation of general complex networks is not enough for explaining certain problems, such as collective actions. Considering the effectiveness of hypernetworks on modeling real-world complex networks, in this paper, we proposed a hypernetwork-based Pólya urn model that considers the effect of group identity. The mathematical deduction and simulation experiments show that social influence provides a strong imitation environment for individuals, which can prevent the dynamics from being self-correcting. Additionally, the unpredictability of the social system increases with growing social influence, and the effect of group identity can moderate market inequality caused by individual preference and social influence. The present work provides a modeling basis for a better understanding of the logic of collective dynamics.

Suppression of beta oscillations by delayed feedback in a cortex-basal ganglia-thalamus-pedunculopontine nucleus neural loop model.

Excessive neural synchronization of neural populations in the beta (ß) frequency range (12-35 Hz) is intimately related to the symptoms of hypokinesia in Parkinson's disease (PD). Studies have shown that delayed feedback stimulation strategies can interrupt excessive neural synchronization and effectively alleviate symptoms associated with PD dyskinesia. Work on optimizing delayed feedback algorithms continues to progress, yet it remains challenging to further improve the inhibitory effect with reduced energy expenditure. Therefore, we first established a neural mass model of the cortex-basal ganglia-thalamus-pedunculopontine nucleus (CBGTh-PPN) closed-loop system, which can reflect the internal properties of cortical and basal ganglia neurons and their intrinsic connections with thalamic and pedunculopontine nucleus neurons. Second, the inhibitory effects of three delayed feedback schemes based on the external globus pallidum (GPe) on ß oscillations were investigated separately and compared with those based on the subthalamic nucleus (STN) only. Our results show that all four delayed feedback schemes achieve effective suppression of pathological ß oscillations when using the linear delayed feedback algorithm. The comparison revealed that the three GPe-based delayed feedback stimulation strategies were able to have a greater range of oscillation suppression with reduced energy consumption, thus improving control performance effectively, suggesting that they may be more effective for the relief of Parkinson's motor symptoms in practical applications.

Genome-Wide Analysis of Family I84 Protease Inhibitor Genes in Three Bivalves Reveals Important Information About the Protein Family's Evolution.

Family I84 serine protease inhibitors are believed to be mollusk specific proteins involved in host defense. The molecular evolution of the family, however, remains to be understood. In this study, the genes of Family I84 protease inhibitors in 3 bivalves, Crassostrea gigas, Crassostrea virginica and Tegillarca granosa, were analyzed at the genomic level. A total of 66 Family I84 genes (22 in C. gigas, 28 in C. virginica and 16 in T. granosa) were identified from the 3 species. They distributed unevenly in the genomes involving 4 chromosomes in C. gigas and 5 chromosomes in C. virginica and T. granosa and some genes were tandemly duplicated. Most genes had 3 exons with 12 genes having 4 exons and 1 gene having 2 exons. All genes but 1 from C. gigas and 1 from T. granosa encoded peptides with a signal sequence at the N-terminus, and the properties of the predicted mature molecules were similar. Four conserved motifs were identified in the 66 amino acid sequences. Collinear analysis revealed higher collinearity between the 2 oyster species in general genes and in Family I84 genes. Phylogenetic analysis of the 66 genes with those previously reported from 3 other bivalves and 1 gastropod showed that Family I84 protease inhibitor genes from the same species tended to be grouped together in terminal branches of the constructed Maximum likelihood tree, but most internal nodes were poorly supported by the bootstrap values. In addition, differences in expression patterns between the genes of a same species were observed in the developmental stages and tissues of C. gigas and T. granosa. Moreover, the co-expression of genes within Family I84 and Family I84 genes with non-Family I84 were also detected in C. gigas and T. granosa. These results suggested that Family I84 protease inhibitor genes evolved by active duplications and structural and functional diversifications after the speciation of related mollusks, and the diversified protease inhibitor family was likely multifunctional.

Improved control effect of pathological oscillations by using delayed feedback stimulation in neural mass model with pedunculopontine nucleus.

BACKGROUND: The role of delayed feedback stimulation in the discussion of Parkinson's disease (PD) has recently received increasing attention. Stimulation of pedunculopontine nucleus (PPN) is an emerging treatment for PD. However, the effect of PPN in regulating PD is ignored, and the delayed feedback stimulation algorithm is facing some problems in parameter selection. METHODS: On the basis of a neural mass model, we established a new network for PPN. Four types of delayed feedback stimulation schemes were designed, such as stimulating subthalamic nucleus (STN) with the local field potentials (LFPs) of STN nucleus, globus pallidus (GPe) with the LFPs of Gpe nucleus, PPN with the LFPs of Gpe nucleus, and STN with the LFPs of PPN nucleus. RESULTS: In this study, we found that all four kinds of delayed feedback schemes are effective, suggesting that the algorithm is simple and more effective in experiments. More specifically, the other three control schemes improved the control performance and reduced the stimulation energy expenditure compared with traditional stimulating STN itself only. CONCLUSION: PPN stimulation can affect the new network and help to suppress pathological oscillations for each neuron. We hope that our results can gain an insight into the future clinical treatment.

MicroRNA-646 inhibits the proliferation of ovarian granulosa cells via insulin-like growth factor 1 (IGF-1) in polycystic ovarian syndrome (PCOS).

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is a common endocrinopathy in women. MicroRNAs (miRNAs) have been proven to play a crucial role in balancing the proliferation and apoptosis of granulosa cells (GCs) in PCOS. MATERIAL AND METHODS: The miRNA of PCOS was screened by bioinformatics analysis, and microRNA 646 (miR-646) was found to be involved in insulin-related pathways by enrichment analysis. The cell counting kit-8 (CCK-8), cell colony formation, and the 5-ethynyl-2'-deoxyuridine (EdU) assays were used to explore the effect of miR-646 on proliferation of GCs, flow cytometry was used to measure the cell cycle and apoptosis, and Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to explore the biological mechanism of miR-646. The human ovarian granulosa cells KGN were selected by measuring the miR-646 and via insulin-like growth factor 1 (IGF-1) levels and used for cell transfection. RESULTS: Overexpressed miR-646 inhibited KGN cell proliferation, and silenced miR-646 advanced it. Most cells were arrested in the S phase of cell cycle with overexpressed-miR-646, while after silencing miR-646, cells were arrested in the G2/M phase. And the miR-646 mimic raised apoptosis in KGN cells. Also, a dual-luciferase reporter proved the regulation effect of miR-646 on IGF-1, miR-646 mimic inhibited IGF-1, and miR-646 inhibitor advanced IGF-1. The cyclin D1, cyclin-dependent kinase 2 (CDK2), and B-cell CLL/lymphoma 2 (Bcl-2) levels were inhibited with overexpressed-miR-646, while silenced-miR-646 promoted their expression, and the bcl-2-like protein 4 (Bax) level was the opposite. This study found that silenced-IGF1 antagonized the promotive effect of the miR-646 inhibitor on cell proliferation. CONCLUSIONS: MiR-646 inhibitor treatment can promote the proliferation of GCs by regulating the cell cycle and inhibiting apoptosis, while silenced-IGF-1 antagonizes it.

The effect of sitagliptin combined with rosiglitazone on autophagy and inflammation in polycystic ovary syndrome by regulating PI3K/AKT/mTOR and TLR4/NF-κB pathway.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder. Sitagliptin (Sit) and rosiglitazone (Ros) are widely used to treat PCOS, but the mechanism is unclear. This study explored the mechanism that Sit and Ros inhibited autophagy and inflammation in PCOS. In this study, 50 female SD rats were divided into 5 groups (n = 10): control, PCOS, Sit, Ros, and Sit+Ros group. The body weight and ovarian weight were measured 2 h after the last administration, and fasting blood glucose, insulin levels were determined. Lipid metabolism and pathological changes were detected by an automatic biochemical analyzer and HE staining. Sex hormone, oxidative stress and inflammatory levels were detected by ELISA. PCR detected IL-18, TNF-α, IL-6, IL-1ß, ATG3, and ATG12 mRNA. The PI3K/AKT/mTOR, TLR4/NF-κB pathway and autophagy-related proteins were detected by western blot. Finally, the number of autophagolysosomes was detected by transmission electron microscopy. Sit or Ros alone reduced body weight, ovarian weight, fasting blood glucose, and insulin levels in PCOS rats. It also improved lipid metabolism, sex hormone levels, oxidative stress and pathological changes, restored the estrous cycle, and corpus luteum quantity. In addition, it could reduce the levels of IL-18, TNF-α, IL-6, IL-1ß, ATG3, and ATG12 mRNA, inhibit the expression of Beclin1, LC3, PI3K/AKT/mTOR, and TLR4/NF-κB pathway proteins. The Sit+Ros group was more effective than single administration. In conclusion, Sit+Ros inhibited the PI3K/AKT/mTOR, TLR4/NF-κB pathways, thereby inhibiting the autophagy and inflammation of PCOS rats, which will provide a theoretical basis for PCOS.