Fangchinoline inhibits mouse oocyte meiosis by disturbing MPF activity.

Fangchinoline (FA) is an alkaloid derived from the traditional Chinese medicine Fangji. Numerous studies have shown that FA has a toxic effect on various cancer cells, but little is known about its toxic effects on germ cells, especially oocytes. In this study, we investigated the effects of FA on mouse oocyte maturation and its potential mechanisms. Our results showed that FA did not affect meiosis resumption but inhibited the first polar body extrusion. This inhibition is not due to abnormalities at the organelle level, such as chromosomes and mitochondrial, which was proved by detection of DNA damage and reactive oxygen species Further studies revealed that FA arrested the oocyte at the metaphase I stage, and this arrest was not caused by abnormal kinetochore-microtubule attachment or spindle assembly checkpoint activation. Instead, FA inhibits the activity of anaphase-promoting complexes (APC/C), as evidenced by the inhibition of CCNB1 degeneration. The decreased activity of APC/C may be due to a reduction in CDC25B activity as indicated by the high phosphorylation level of CDC25B (Ser323). This may further enhance Maturation-Promoting Factor (MPF) activity, which plays a critical role in meiosis. In conclusion, our study suggests that the metaphase I arrest caused by FA may be due to abnormalities in MPF and APC/C activity.

[Clinical study of Bushen Culuan Formula in treatment of ovulatory disorder infertility caused by hyperprolactinemia].

This paper aims to study the therapeutic effect and safety of Bushen Culuan Formula in the treatment of patients with infertility caused by hyperprolactinemia. Sixty patients with infertility caused by hyperprolactinemia of kidney deficiency and blood stasis were divided into the treatment group(Bushen Culuan Formula + Bromocriptine Mesylate Tablets placebo) and the control group(Bromocriptine Mesylate Tablets + Bushen Culuan Formula placebo), and ovulation rate, pregnancy rate, serum sex hormones, basal body temperature(BBT), and traditional Chinese medicine(TCM) symptom scores were observed. The results showed the clinical effective rate was 90.00% in the treatment group and 80.00% in the control group. The treatment group was able to significantly reduce the PRL level and increase the pregnancy rate, and it was superior to the control group in increasing the BBT biphasic ratio, improving the TCM symptom scores, and enhancing the ovulation rate. The results show that Bushen Culuan Formula is safe and reliable in treating ovulatory disorder infertility caused by hyperprolactinemia, with remarkable effects.

[Examples of Professor MA Kun's treatment of infertility caused by uterine fibroids using method of tonifying kidney and activating blood].

Uterine fibroids are a prevalent factor that impacts fertility in women of reproductive age. This study discusses the theoretical foundation and formula principles of Professor MA Kun's clinical treatment for infertility caused by uterine fibroids. The kidney stores essence and is responsible for reproduction, while blood serves as a vital material basis for women's physiological functions. Kidney deficiency is the fundamental pathogenesis of infertility, and imbalances in kidney Qi and essence or deficiencies in kidney Yin and Yang can result in blood stasis. Blood stasis plays a significant role throughout this condition by impeding the flow of blood, which is crucial for nourishing Qi. Therefore, both kidney deficiency and blood stasis are key factors contributing to infertility caused by uterine fibroids. Professor MA Kun treats infertility caused by uterine fibroids using an approach that involves tonifying the kidneys and activating blood circulation based on changes in Qi and blood during the menstrual cycle as well as follicular growth processes. By identifying stage-specific evidence, appropriate treatments can be applied accordingly. During menstruation when the uterus opens and menstrual blood flows out, promoting follicular development through nourishing kidney Yin and activating blood circulation becomes essential. In later stages of menstruation, additional measures are taken to remove blood stasis, alleviate symptoms, disperse knots, attack pathogens while simultaneously replenishing vital energy. During intermenstrual periods when Yin holds greater importance than Yang, tonifying the kidneys and activating blood circulation helps facilitate smooth discharge of eggs by promoting transformation between Yin and Yang energies. Premenstrual period to warm kidney Yang to promote pregnant egg implantation, and at the same time to dredge the liver and regulate Qi, Qi elimination stagnation, complementary in the line, with the symptoms of additional subtractions. Clinical effect is remarkable, for the reference of colleagues.

[Study on mechanism of regulation of sex hormones in treatment of hyperprolactinemia-induced ovulatory disorder infertility with Bushen Culuan Formula].

Transcriptomics was used to investigate the mechanism of action of Bushen Culuan Formula in the treatment of infertility caused by hyperprolactinemia(HPRL), and animal experiments were carried out to verify the results. After establishing an animal model of HPRL-induced infertility, the mice were divided into normal group, model group, Bushen Culuan Formula groups with high-, medium-, and low-doses, and bromocriptine group, and they were observed in terms of the estrous cycle, gonadal index, serum sex hormones, morphology of ovary and mammary gland, follicle count, and fertility. The results showed that the Bushen Culuan Formula could effectively restore the estrous cycle, down-regulate the levels of prolactin(PRL), follicle-stimulating hormone(FSH), and luteinizing hormone(LH), up-regulate the level of estradiol(E_2), increase the number of primordial follicles and sinus follicles, and improve the ovulation rate and fertility of mice. Through RNA sequencing combined with biosignature analysis, Bushen Culuan Formula may regulate the metabolism of lipids, antioxidant enzymes, and other substances in the cells of the ovary and pituitary gland through the signaling pathways of cAMP-PKA, Kiss-1/GPR54, and Hippo and exert therapeutic effects. The results of animal experiments showed that Bushen Culuan Formula could up-regulate serum dopamine(DA) level and pituitary DRD2 expression, down-regulate hypothalamus and ovary cAMP levels, as well as protein expressions of the pituitary gland and ovary PKA, CREB, and p-CREB, and treat HPRL-induced infertility by regulating the cAMP-PKA signaling pathway.

[Bushen Culuan Formula in treatment of infertility caused by polycystic ovary syndrome].

This study aims to observe the efficacy and safety of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS) and to explore the mechanism using metabolomics. Ninety-four patients with infertility caused by PCOS with the syndrome of kidney deficiency and blood stasis were selected and assigned into treatment and control groups(n=47). The basal body temperature(BBT) was measured, and B-ultrasonography was employed to monitor follicles, ovarian volume, endometrium, ovulation, and pregnancy. The serum levels of sex hormones including follicle-stimulating hormone(FSH), luteinizing hormone(LH), prolactin(PRL), estradiol(E_2), progestin(P), testosterone(T), free testosterone(FT), androstenedione(A2), inhibin B(INHB), and anti-Müllerian hormone(AMH) were measured. The coagulation function, traditional Chinese medicine(TCM) symptom scores, blood and urine routine, liver and kidney functions and other safety indicators were determined. Metabolomics was employed to comparatively analyze the serum metabolites of 26 patients(13 patients in each group) in the clinical study. The results showed that the total response rate and pregnancy rate of the treatment group were higher than those of the control group(P<0.001), suggesting that Bushen Culuan Formula regulated the sex hormones and ovarian function. Specifically, it reduced the levels of LH, T, FT, A2, and INHB(P<0.05 or P<0.01) and the LH/FSH ratio(P<0.05), elevated the level of P(P<0.05), promoted ovulation, increased endothelial thickness, and lowered TCM symptom scores without causing adverse reactions. A total of 24 differential metabolites were screened by metabolomics, and there were correlations between sex hormones and differential metabolites in the PCOS-induced infertility patients with kidney deficiency and blood stasis. In conclusion, Bushen Culuan Formula may regulate hormone levels through lipid and amino acid metabolism.

Regulation of FSP1 myristoylation by NADPH: A novel mechanism for ferroptosis inhibition.

Excitotoxicity is a prevalent pathological event in neurodegenerative diseases. The involvement of ferroptosis in the pathogenesis of excitotoxicity remains elusive. Transcriptome analysis has revealed that cytoplasmic reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels are associated with susceptibility to ferroptosis-inducing compounds. Here we show that exogenous NADPH, besides being reductant, interacts with N-myristoyltransferase 2 (NMT2) and upregulates the N-myristoylated ferroptosis suppressor protein 1 (FSP1). NADPH increases membrane-localized FSP1 and strengthens resistance to ferroptosis. Arg-291 of NMT2 is critical for the NADPH-NMT2-FSP1 axis-mediated suppression of ferroptosis. This study suggests that NMT2 plays a pivotal role by bridging NADPH levels and neuronal susceptibility to ferroptosis. We propose a mechanism by which the NADPH regulates N-myristoylation, which has important implications for ferroptosis and disease treatment.

Electroacupuncture improves apoptosis of nucleus pulposus cells via the IL-22/JAK2-STAT3 signaling pathway in a rat model of cervical intervertebral disk degeneration.

BACKGROUND: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). METHODS: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). RESULTS: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1ß, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. CONCLUSION: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.

One-step hydrothermal synthesis of vanadium dioxide/carbon core-shell composite with improved ammonium ion storage for aqueous ammonium-ion battery.

Aqueous nonmetallic ion batteries have garnered significant interest due to their cost-effectiveness, environmental sustainability, and inherent safety features. Specifically, ammonium ion (NH4+) as a charge carrier has garnered more and more attention recently. However, one of the persistent challenges is enhancing the electrochemical properties of vanadium dioxide (VO2) with a tunnel structure, which serves as a highly efficient NH4+ (de)intercalation host material. Herein, a novel architecture, wherein carbon-coated VO2 nanobelts (VO2@C) with a core-shell structure are engineered to augment NH4+ storage capabilities of VO2. In detail, VO2@C is synthesized via the glucose reduction of vanadium pentoxide under hydrothermal conditions. Experimental results manifest that the introduction of the carbon layer on VO2 nanobelts can enhance mass transfer, ion transport and electrochemical kinetics, thereby culminating in the improved NH4+ storage efficiency. VO2@C core-shell composite exhibits a remarkable specific capacity of ∼300 mAh/g at 0.1 A/g, which is superior to that of VO2 (∼238 mAh/g) and various other electrode materials used for NH4+ storage. The NH4+ storage mechanism can be elucidated by the reversible NH4+ (de)intercalation within the tunnel of VO2, facilitated by the dynamic formation and dissociation of hydrogen bonds. Furthermore, when integrated into a full battery with polyaniline (PANI) cathode, the VO2@C//PANI full battery demonstrates robust electrochemical performances, including a specific capacity of ∼185 mAh·g-1 at 0.2 A·g-1, remarkable durability of 93 % retention after 1500 cycles, as well as high energy density of 58 Wh·kg-1 at 5354 W·kg-1. This work provides a pioneering approach to design and explore composite materials for efficient NH4+ storage, offering significant implications for future battery technology enhancements.

Nitrogen migration and transformation during re-suspension and photo-induction in landscape water replenished by reclaimed water.

Sediment re-suspension plays a crucial role in releasing endogenous nitrogen and greenhouse gases in shallow urban waters. However, the impacts of repeated re-suspension and photo-induced processes on migration and transformation from endogenous nitrogen, as well as the emission of greenhouse gases, remain unclear. This study simulated three conditions: re-suspension (Rs), re-suspension combined with ultravioletirradiation (Rs + UV), and ultraviolet irradiation (UV). The findings revealed that both repeated sediment re-suspension and exposure to UV light altered the characteristics of surface sediments. Decrease of convertible nitrogen in sediments, leading to the release of ion-exchangeable nitrogen (IEF-N) into NH4+-N and NO3--N, influenced greenhouse gas production differently under various conditions. The study observed the highest concentration of dissolved N2O in under UV irradiation, positively correlated with NO2--N and NO3--N. Re-suspension increased the turbidity of the overlying water and accelerated nitrification, resulting in the highest NO3--N concentration and the lowest dissolved N2O concentration. Additionally, in the Rs + UV dissolved N2O maintained the higher concentrations than in Rs, with greatest amount of N conversion in surface sediments, and a 59.45% reduction in IEF-N. The production of N2O during re-suspension was mainly positively correlated with NH4+-N in the overlying water. Therefore, this study suggest that repeated re-suspension and light exposure significantly influence nitrogen migration and transformation processes in sediment, providing a theoretical explanation for the eutrophication of water and greenhouse gas emissions.

Multidirectional Intervention of Chinese Herbal Medicine in the Prevention and Treatment of Atherosclerosis: From Endothelial Protection to Immunomodulation.

Atherosclerosis is a significant risk factor for developing cardiovascular disease and a leading cause of death worldwide. The occurrence of atherosclerosis is closely related to factors such as endothelial injury, lipid deposition, immunity, and inflammation. Conventional statins, currently used in atherosclerosis treatment, have numerous adverse side effects that limit their clinical utility, prompting the urgent need to identify safer and more effective therapeutic alternatives. Growing evidence indicates the significant potential of Chinese herbs in atherosclerosis treatment. Herbal monomer components, such as natural flavonoid compounds extracted from herbs like Coptis chinensis and Panax notoginseng, have been utilized for their lipid-lowering and inflammation-inhibiting effects in atherosclerosis treatment. These herbs can be used as single components in treating diseases and with other Chinese medicines to form herbal combinations. This approach targets the disease mechanism in multiple ways, enhancing the therapeutic effects. Thus, this review examines the roles of Chinese herbal medicine monomers and Chinese herbal compounds in inhibiting atherosclerosis, including regulating lipids, improving endothelial function, reducing oxidative stress, regulating inflammation and the immune response, and apoptosis. By highlighting these roles, our study offers new perspectives on atherosclerosis treatment with Chinese herbs and is anticipated to contribute to advancements in related research fields.

Respiratory oscillometry with CT image analysis in idiopathic pulmonary fibrosis following single lung transplant.

Oscillometry is an emerging pulmonary function testing tool that is conducted during tidal breaths with minimal patient effort. It is highly sensitive to changes in lung mechanics. Oscillometry was recently shown to be highly associated with disease severity in idiopathic pulmonary fibrosis (IPF). The usefulness of oscillometry after single lung transplant in IPF patients is not well understood. Our study demonstrated that oscillometry can detect changes in the graft despite presence of a native fibrotic lung to provide useful information to complement spirometry.

HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis.

Background: BRCA2 plays a key role in homologous recombination. However, information regarding its mutations in Chinese patients with breast cancer remains limited. Objectives: This study aimed to assess the clinicopathological characteristics of BRCA2 mutation breast cancer and explore the mutation's effect on hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer survival in China. Design: This hospital-based cohort study prospectively included 629 women with breast cancer diagnosed from 2008 to 2023 at Zhejiang Cancer Hospital in China. Methods: We compared the clinicopathological characteristics and metastatic patterns and analysed the invasive disease-free survival (iDFS), distant relapse-free survival (DRFS) and first-line progression-free survival (PFS1) of patients with HR-positive/HER2-negative breast cancer according to BRCA2 mutations. Results: Among the 629 patients, 78 had BRCA2 mutations (12.4%) and 551 did not (87.6%). The mean age at diagnosis was lower in the BRCA2 mutation breast cancer group than in the non-mutation breast cancer group (38.91 versus 41.94 years, p = 0.016). BRCA2 mutation breast cancers were more likely to be lymph node-positive than non-mutation breast cancers (73.0% versus 56.6%, p = 0.037). The pathological grade was higher in 47.1% of BRCA2 mutation breast cancers than in 29.6% of non-mutation breast cancers (p = 0.014). The proportions of patients with BRCA2 mutations who developed contralateral breast cancer (19.2% versus 8.8%, p = 0.004), breast cancer in the family (53.8% versus 38.3%, p = 0.009) and ovarian cancer in the family (7.6% versus 2.4%, p = 0.022) were higher than those of patients without the mutation. The median follow-up time was 92.78 months. Multivariate analysis showed that BRCA2 mutation was not associated with poorer iDFS [hazard ratio = 0.9, 95% confidence interval (CI) = 0.64-1.27, p = 0.56] and poorer distant relapse-free survival (DRFS) (hazard ratio = 1.09, 95% CI = 0.61-1.93, p = 0.76). There was no significant difference between the two groups with regard to metastatic patterns in the advanced disease setting. In the first-line metastatic breast cancer setting, PFS1 expression was broadly similar between the two groups irrespective of chemotherapy or endocrine therapy. Conclusion: HR-positive/HER2-negative breast cancer with BRCA2 mutations differs from those without mutations in clinical behaviour and reflects more aggressive tumour behaviour. Our results indicate that BRCA2 mutations have no significant effect on the survival of Chinese women with HR-positive/HER2-negative breast cancer.

Substance P in the medial amygdala regulates aggressive behaviors in male mice.

Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeATac1 neurons) are activated during aggressive behaviors in male mice. We identified MeATac1 neurons as a key mediator of aggression and found that MeATac1→ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits.

Improving water quality and mitigating CH4 and N2O production in urban landscape water simultaneously by optimizing calcium peroxide dosage.

Recent studies show that greenhouse gas (GHG) emissions from urban landscape water are significant and cannot be overlooked, underscoring the need to develop effective strategies for mitigating GHG production from global freshwater systems. Calcium peroxide (CaO2) is commonly used as an eco-friendly reagent for controlling eutrophication in water bodies, but whether CaO2 can reduce GHG emissions remains unclear. This study investigated the effects of CaO2 dosage on the production of methane (CH4) and nitrous oxide (N2O) in urban landscape water under anoxic conditions during summer. The findings reveal that CaO2 addition not only improved the physicochemical and organoleptic properties of simulated urban landscape water but also reduced N2O production by inhibiting the activity of denitrifying bacteria across various dosages. Moreover, CaO2 exhibited selective effects on methanogens. Specifically, the abundance of acetoclastic methanogen Methanosaeta and methylotrophic methanogen Candidatus_Methanofastidiosum increased whereas the abundance of the hydrogenotrophic methanogen Methanoregula decreased at low, medium, and high dosages, leading to higher CH4 production at increased CaO2 dosage. A comprehensive multi-objective evaluation indicated that an optimal dosage of 60 g CaO2/m2 achieved 41.21 % and 84.40 % reductions in CH4 and N2O production, respectively, over a 50-day period compared to the control. This paper not only introduces a novel approach for controlling the production of GHGs, such as CH4 and N2O, from urban landscape water but also suggests a methodology for optimizing CaO2 dosage, providing valuable insights for its practical application.

The transgenerational effects of maternal low-protein diet during lactation on offspring.

Environmental factors such as diet and lifestyle can influence the health of both mothers and offspring. However, its transgenerational transmission and underlying mechanisms remain largely unknown. Here, using a maternal lactation-period low-protein diet (LPD) mouse model, we show that maternal LPD during lactation causes decreased survival and stunted growth, significantly reduces ovulation and litter size, and alters the gut microbiome in the female LPD-F1 offspring. The transcriptome of LPD-F1 metaphase II (MII) oocytes shows that differentially expressed genes are enriched in female pregnancy and multiple metabolic processes. Moreover, maternal LPD causes early stunted growth and impairs metabolic health, which is transmitted over two generations. The methylome alteration of LPD-F1 oocytes can be partly transmitted to the F2 oocytes. Together, our results reveal that LPD during lactation transgenerationally affects offspring health, probably via oocyte epigenetic changes.

Latent profiles of academic resilience in undergraduate nursing students and their association with resilience and self-efficacy.

AIM: This study aimed to investigate the heterogeneity of academic resilience among nursing students using latent profile analysis and its associated influencing factors. BACKGROUND: Nursing students experience higher levels of stress compared to their peers in other professions, and the cultivation of academic resilience plays a pivotal role in their ability to effectively cope with this stress. Academic resilience not only facilitates success in the face of academic adversity but also contributes to the promotion of mental well-being among nursing students. However, the current research on the academic resilience of nursing students has predominantly focused on a scale-centered total score approach, disregarding individual variability, and hindering the development to inform personalized interventions for enhancing academic resilience. DESIGN: A cross-sectional study. METHODS: A convenience sampling method was used to collect a total of 644 nursing students from two medical schools in Guangzhou City. The participants were recruited through an online survey conducted from January to March 2023. The questionnaires consisted of a general information form, the Chinese version of the Academic Resilience Scale-30 (C-ARS-30), the 10-item Connor Davidson Resilience Scale (CD-RISC-10), and the General Self-Efficacy Scale (GSES). Latent profile analysis was used to identify distinct categories of academic resilience among nursing students, and influencing factors were examined through ordinal logistic regression analysis. RESULTS: The academic resilience levels of nursing students can be divided into three potential categories: 'low academic resilience' (13.0%), 'moderate academic resilience' (70.0%), and 'high academic resilience' (17.0%). Level of grade, GPA, self-reported physical health level, resilience and self-efficacy were significantly influenced the different categories of academic resilience of nursing students (P<0.05). CONCLUSIONS: The majority of undergraduate nursing students were placed in the moderate academic resilience group, however, educational institutions should pay special attention to nursing students demonstrating low levels. Regular assessments of academic resilience are recommended, and personalized interventions should be tailored to address specific academic resilience characteristics across different grades of nursing students. Strategies aimed at enhancing academic resilience among nursing students may include improvements in GPA performance, attention to physical health, and the reinforcement of resilience and self-efficacy.

Hydrogen Source Tuned Regiodivergent Asymmetric Hydroalkylations of 2-Substituted 1,3-Dienes with Aldehydes by Cobalt-Catalysis.

Catalytic methods allowing for the reliable prediction and control of diverse regioselectivity along with the control of enantioselectivity to access different regio- and enantiomers by switching the least reaction parameters are one of the most attractive ways in organic synthesis, which provide access to diverse enantioenriched architectures from identical starting materials. Herein, a Co-catalyzed regiodivergent and enantioselective reductive hydroalkylation of 1,3-dienes with aldehydes has been achieved, furnishing different enantioenriched homoallylic alcohol architectures in good levels of enantioselectivity. The reaction features the switch of regioselectivity tuned by the selection of proton source. The use of an acid as proton source provided asymmetric 1,2-hydroalkylation products under reductive conditions, yet asymmetric 4,3-hydroalkylation products were obtained with silane as hydride source. This catalytic protocol allows for the access of homoallylic alcohols with two continuous saturated carbon centers in good levels of regio-, diastereo-, and enantioselectivity.

Loss of UBE2S causes meiosis I arrest with normal spindle assembly checkpoint dynamics in mouse oocytes.

The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.

Bioinformatics identification of potential biomarkers and therapeutic targets for ischemic stroke and vascular dementia.

Ischemic stroke and vascular dementia, as common cerebrovascular diseases, with the former causing irreversible neurological damage and the latter causing cognitive and memory impairment, are closely related and have long received widespread attention. Currently, the potential causative genes of these two diseases have yet to be investigated, and effective early diagnostic tools for the diseases have not yet emerged. In this study, we screened new potential biomarkers and analyzed new therapeutic targets for both diseases from the perspective of immune infiltration. Two gene expression profiles on ischemic stroke and vascular dementia were obtained from the NCBI GEO database, and key genes were identified by LASSO regression and SVM-RFE algorithms, and key genes were analyzed by GO and KEGG enrichment. The CIBERSORT algorithm was applied to the gene expression profile species of the two diseases to quantify the 24 subpopulations of immune cells. Moreover, logistic regression modeling analysis was applied to illustrate the stability of the key genes in the diagnosis. Finally, the key genes were validated using RT-PCR assay. A total of 105 intersecting DEGs genes were obtained in the 2 sets of GEO datasets, and bioinformatics functional analysis of the intersecting DEGs genes showed that GO was mainly involved in the purine ribonucleoside triphosphate metabolic process，respiratory chain complex，DNA-binding transcription factor binding and active transmembrane transporter activity. KEGG is mainly involved in the Oxidative phosphorylation, cAMP signaling pathway. The LASSO regression algorithm and SVM-RFE algorithm finally obtained three genes, GAS2L1, ARHGEF40 and PFKFB3, and the logistic regression prediction model determined that the three genes, GAS2L1 (AUC: 0.882), ARHGEF40 (AUC: 0.867) and PFKFB3 (AUC: 0.869), had good diagnostic performance. Meanwhile, the two disease core genes and immune infiltration were closely related, GAS2L1 and PFKFB3 had the highest positive correlation with macrophage M1 (p < 0.001) and the highest negative correlation with mast cell activation (p = 0.0017); ARHGEF40 had the highest positive correlation with macrophage M1 and B cells naive (p < 0.001), the highest negative correlation with B cell memory highest correlation (p = 0.0047). RT-PCR results showed that the relative mRNA expression levels of GAS2L1, ARHGEF40, and PFKFB3 were significantly elevated in the populations of both disease groups (p < 0.05). Immune infiltration-based models can be used to predict the diagnosis of patients with ischemic stroke and vascular dementia and provide a new perspective on the early diagnosis and treatment of both diseases.