Tetracycline degradation by dual-frequency ultrasound combined with peroxymonosulfate.

Tetracycline has received a great deal of interest for the harmful effects of substance abuse on ecosystems and humanity. The effects of different processes on the degradation of tetracycline were compared, with dual-frequency ultrasound (DFUS) in combination with peroxymonosulfate (PMS) being the most effective for the tetracycline degradation. Free radical scavenging experiments showed that O2∙-,SO4∙- and •OH were the main reactive radicals in the degradation of tetracycline. According to the major intermediates of tetracycline degradation identified, three possible degradation pathways were proposed, which are of significance for translational studies of tetracycline degradation. Notably, these intermediates were found to be significantly less toxicity. The number of active bubbles in the degradation vessel was calculated using a semi-empirical formula, and a higher value of 1.44 × 108 L-1s-1 of bubbles was obtained when using dual-frequency ultrasound at 20 kHz (210 W/L) and 80 kHz (85.4 W/L). Therefore, compared to 20 kHz, although the yield of strong oxidizing substances from individual active bubbles decreased slightly, a significant increment of the number of active bubbles still resulted in a higher synergistic effect, and the combination of DFUS and PMS should be effective in promoting the generation of reactive free radicals and mass transfer processes within the degradation vessel, which provides a method for efficient removal of tetracycline from wastewater.

Oncogene-driven non-small cell lung cancers in patients with a history of smoking lack smoking-induced mutations.

Non-small cell lung cancers (NSCLCs) in non-smokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in non-smokers, alterations in these "non-smoking-related oncogenes" (NSROs) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared to typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and non-smokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC datasets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to regulation of the cell cycle. These findings suggest that, while the genomic landscape is similar between NSRO-driven NSCLC in smokers and non-smokers, smoking still affects the tumor phenotype independently of genomic alterations.

N4-Allylcytidine: a new nucleoside analogue for RNA labelling and chemical sequencing.

RNA labelling has become indispensable in studying RNA biology. Nucleoside analogues with a chemical sequencing power represent desirable RNA labelling molecules because precise labelling information at base resolution can be obtained. Here, we report a new nucleoside analogue, N4-allylcytidine (a4C), which is able to tag RNA through both in vitro and in vivo pathways and further specifically reacts with iodine to form 3, N4-cyclized cytidine (cyc-C) in a catalyst-free, fast and complete manner. Full spectroscopic characterization concluded that cyc-C consisted of paired diastereoisomers with opposite chiral carbon centers in the fused 3, N4-five-membered ring. During RNA reverse transcription into complementary DNA, cyc-C induces base misincorporation due to the disruption of canonical hydrogen bonding by the cyclized structure and thus can be accurately identified by sequencing at single base resolution. With the chemical sequencing rationale of a4C, successful applications have been performed including pinpointing N4-methylcytidine methyltransferases' substrate modification sites, metabolically labelling mammalian cellular RNAs, and mapping active cellular RNA polymerase locations with the chromatin run-on RNA sequencing technique. Collectively, our work demonstrates that a4C is a promising molecule for RNA labelling and chemical sequencing and expands the toolkit for studying sophisticated RNA biology.

Thermal and Magnetic Dual-Responsive Catheter-Assisted Shape Memory Microrobots for Multistage Vascular Embolization.

Catheters navigating through complex vessels, such as sharp turns or multiple U-turns, remain challenging for vascular embolization. Here, we propose a novel multistage vascular embolization strategy for hard-to-reach vessels that releases untethered swimming shape-memory magnetic microrobots (SMMs) from the prior catheter to the vessel bifurcation. SMMs, made of organo-gel with magnetic particles, ensure biocompatibility, radiopacity, thrombosis, and fast thermal and magnetic responses. An SMM is initially a linear shape with a 0.5-mm diameter at 20 °C inserted in a catheter. It transforms into a predetermined helix within 2 s at 38 °C blood temperature after being pushed out of the catheter into the blood. SMMs enable agile swimming in confined and tortuous vessels and can swim upstream using helical propulsion with rotating magnetic fields. Moreover, we validated this multistage vascular embolization in living rabbits, completing 100-cm travel and renal artery embolization in 2 min. After 4 weeks, the SMMs maintained the embolic position, and the kidney volume decreased by 36%.

The relationship between duration of infertility and clinical outcomes of intrauterine insemination for younger women: a retrospective clinical study.

BACKGROUND: The objective of this research was to elucidate the association between the length of infertility and the outcomes of intrauterine insemination (IUI) in women of varying ages - a topic that has been the subject of investigation for numerous years, yet lacks a definitive consensus. METHODS: A retrospective cohort investigation involving 5268 IUI cycles was undertaken at the Reproductive Medicine Center of Nanjing Drum Tower Hospital from 2016 to 2022. Utilizing the smooth fitting curve along with threshold and saturation effect analysis, the correlation between infertility duration and IUI clinical pregnancy rates was discerned. Moreover, patients were bifurcated into two cohorts based on their respective infertility durations. A secondary examination was also performed employing propensity-score matching to mitigate the impact of confounding variables. Subsequent threshold and saturation effect analysis was carried out across various subgroups, segmented on the basis of age differentiation. RESULTS: When the duration of infertility was more than 5 years, the clinical pregnancy rate decreased with the increase of infertility duration (aOR: 0.894, 95%CI: 0.817-0.991, p = 0.043). The multivariate regression analysis suggested that longer duration of infertility (≥ 5 years) was significantly correlated with the lower clinical pregnancy rate (aOR: 0.782, 95% CI: 0.643-0.950, p = 0.01). After the propensity-score matching, the clinical pregnancy rate of women with longer infertility duration were also higher. When the duration of infertility was more than 5 years, the clinical pregnancy rate of women younger than 35 years old decreased with the increase of infertility duration (aOR: 0.906, 95%CI: 0.800-0.998, p = 0.043). CONCLUSIONS: The clinical pregnancy rate and live birth rate of IUI in young women (< 35 years old) who have been infertile for more than 5 years significantly decrease with the prolongation of infertility time. Therefore, for young women who have been infertile for more than 5 years, IUI may not be the best choice.

Effectiveness and safety of afatinib, gefitinib, and erlotinib for treatment-naïve elderly patients with epidermal growth factor receptor-mutated advanced non-small-cell lung cancer: a multi-institute retrospective study.

BACKGROUND: In real-world practice, most patients with lung cancer are diagnosed when they are aged ≥65 years. However, clinical trials tend to lack data for the elderly population. Therefore, we aimed to describe the effectiveness and safety of afatinib, gefitinib, and erlotinib for elderly patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC). METHODS: Treatment-naïve patients with EGFR-mutated advanced NSCLC were enrolled at many hospitals in Taiwan. Patient characteristics and the effectiveness and safety of afatinib, gefitinib, and erlotinib were compared. RESULTS: This study enrolled 1,343 treatment-naïve patients with EGFR-mutated advanced NSCLC, of whom 554 were aged <65 years, 383 were aged 65-74 years, 323 were aged 75-84 years, and 83 were aged ≥85 years. For elderly patients, afatinib was more effective, with a median progression-free survival (PFS) of 14.7 months and overall survival (OS) of 22.2 months, than gefitinib (9.9 months and 17.7 months, respectively) and erlotinib (10.8 months and 18.5 months, respectively; PFS: p = 0.003; OS: p = 0.026). However, grade ≥3 adverse events, including skin toxicities, paronychia, mucositis, and diarrhea, were more frequently experienced by patients receiving afatinib than those receiving gefitinib or erlotinib. CONCLUSIONS: This large retrospective study provides real-world evidence of the effectiveness and safety of EGFR-TKIs for elderly patients with EGFR-mutated advanced NSCLC, a population that is often underrepresented in clinical trials and real-world evidence. Afatinib was more effective as a first-line treatment than gefitinib or erlotinib for elderly patients with EGFR-mutated advanced NSCLC.

An RNA Methylation-Sensitive AIEgen-Aptamer Reporting System for Quantitatively Evaluating m6A Methylase and Demethylase Activities.

N6-Methyladenosine (m6A) chemical modification determines the fate of the mammalian cellular mRNA to modulate crucial physiological and pathological processes. Dysregulations of m6A methylase and demethylase have been linked to cancer diseases. Therefore, evaluations of enzyme mutants' activities and related inhibitors for discovery of targeted therapeutic strategies are very necessary. Here, we report an RNA methylation-sensitive fluorescent aptamer reporting assay to measure the catalytic activities of m6A enzymes under various conditions. The rationale is that when an RNA aptamer, named A-Pepper, is methylated at a specific adenosine position to generate m6A-Pepper, the latter displays stronger fluorescence than the former upon binding the ligand, which is an aggregation-induced emission-active luminogen. The fluorescence signal enhancement is linearly proportional to the RNA methylation extent, which is equivalent to the methylase activity. On the contrary, the m6A demethylase activity is measured through calculating the fluorescence signal decrease caused by the switching from m6A-Pepper to A-Pepper. The assay has been successfully applied to quantitatively evaluate the mutation and inhibitor effects on the activities of m6A methylases METTL3/METTL14 and demethylase FTO, and the obtained results are well-consistent with those quantified by the expensive and time-consuming golden standard LC-MS/MS. Our work provides a simple tool capable of detecting m6A enzymes' activities and screening their inhibitors in a rapid, quantitative, cost-effective, and high-throughput manner.

Effect of Elevated Progesterone Levels on hCG Trigger Day on Clinical Pregnancy Outcome in Short-Acting GnRHa Downregulated Cycles.

Background: Previous studies suggested higher serum progesterone (P) levels were strongly associated with a lower clinical pregnancy rate (CPR) for in vitro fertilization-embryo transfer (IVF-ET). However, the effect of increased serum P levels on the day of human chorionic gonadotropin (hCG) administration on clinical outcomes in short-acting gonadotropin-releasing hormone agonist (GnRHa) downregulated IVF-ET cycles remains unclear. Methods: We conducted a retrospective cohort study from January 2017 to December 2021, which included a total of 1664 patients receiving their first short-acting GnRHa IVF-ET cycles at our reproductive medicine centre of Nanjing Drum Tower Hospital. The smooth curve fitting and interaction analysis were employed to analyse the association between the CPR and the serum P levels with different embryo types (cleavage-stage embryo or blastocyst). In addition, total cycles were grouped according to different P levels on the trigger day of hCG administration for further analysis. Results: The CPR of patients with increased serum P level (higher than 1.5 ng/mL) on the hCG day did not decrease. A smoothing curve fitting showed that the CPR did not change obviously with the increase in serum P levels. Subgroup analysis of different types of embryos transferred showed that no correlation was observed between the CPR and serum P levels on the day of hCG administration in cleavage-stage embryo transfer cycles. However, the CPR of patients receiving blastocyst transfer showed a downward trend with the increase in serum P levels. At the same time, an interaction analysis also confirmed that the CPR of blastocyst transfer was more likely to be affected by elevated serum P levels on the hCG day. Conclusion: In the luteal phase short-acting GnRHa downregulated IVF-ET cycles, the elevated serum P levels on the hCG day did not affect the CPR of cleavage-stage embryo transfer but reduced the CPR of blastocyst transfer.

Preshaped 4D Photocurable Ultratough Organogel Microcoils for Personalized Endovascular Embolization.

Endovascular embolization using microcoils can be an effective technique to treat artery aneurysms. However, microcoils with fixed designs are difficult to adapt to all aneurysm types. In this paper, a photocurable ultratough shape memory organogel with a curing time of only 2 s and megapascal-level mechanical properties is proposed. Then, it is used to manufacture the personalized 4D microcoil with a wire diameter of only 0.3 mm. The improved mechanical modulus (511.63 MPa) can reduce the possibility of microcoils' fracture during embolization. Besides, the fast body-temperature-triggering shape memory ability makes the 4D microcoil applicable in vivo. These 4D microcoils are finally delivered into the rabbit, and successfully blocked the blood flow inside different aneurysms, with neoendothelial cells and collagen fibers growing on the microcoil surface snugly, indicating full aneurysm recovery. This 4D organogel microcoil can potentially be used in personalized clinical translation on human beings.

Vincristine exposure impairs mouse oocyte quality by inducing spindle defects and early apoptosis.

Vincristine (VCR) is a microtubule-destabilizing chemotherapeutic agent commonly administered for the treatment of cancers in patients, which can induce severe side effects including neurotoxicity. In context of the effects on female fertility, ovarian toxicity has been found in patients and mice model after VCR exposure. However, the influence of VCR exposure on oocyte quality has not been elucidated. We established VCR exposure in vitro and in vivo model. The results indicated in vitro VCR exposure contributed to failure of oocyte maturation through inducing defects in spindle assembly, activation of SAC, oxidative stress, mitochondrial dysfunction, and early apoptosis, which were confirmed by using in vivo exposure model. Moreover, in vivo VCR exposure caused aneuploidy, reduced oocyte-sperm binding ability, and the number of cortical granules in mouse oocyte cortex. Taken together, this study demonstrated that VCR could cause meiotic arrest and poor quality of mouse oocyte.

Generation and validation of a predictive model for estimating survival among patients with EGFR-mutant non-small cell lung cancer.

Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become the standard therapy for patients with EGFR-mutant non-small cell lung cancer (NSCLC), treatment outcomes vary significantly. Previous studies have indicated that concurrent mutations may compromise the effectiveness of first-line EGFR-TKIs. However, given the high cost of next-generation sequencing, this information is often inaccessible in routine clinical practice. A prediction model based on pre-treatment clinical characteristics may thus offer a more practical solution. This study established a nomogram based on pretreatment clinical characteristics to stratify patients according to optimal treatment strategies. We retrospectively reviewed 761 patients with EGFR-mutant NSCLC who received first- or second-generation EGFR-TKIs at a tertiary referral center between 2010 and 2019. The pretreatment clinical characteristics and progression-free survival data were collected. Using COX proportional hazard regression analysis, we constructed a nomogram based on seven clinically significant prognostic factors: sex, Eastern Cooperative Oncology Group performance status, histology subtype, mutation subtype, stage, and metastasis to the liver and brain. Our nomogram could stratify patients into three groups with different risks for disease progression and was validated in a patient cohort from other hospitals. This risk stratification can provide additional information for determining the optimal first-line treatment strategy for patients with EGFR-mutant NSCLC.

Nasopharyngeal carcinoma patient-derived xenograft mouse models reveal potential drugs targeting cell cycle, mTOR, and autophagy pathways.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) infection. To test preclinical NPC drugs, we established two patient-derived xenograft (PDX) mouse models, EBV-positive PDX-B13 and EBV-negative PDX-Li41, for drug screening. METHODS: Based on next generation sequencing (NGS) studies, PDX-B13 had CCND1 copy number (CN) gain but CDKN2A CN loss, whereas PDX-Li41 had CDKN2A and RB1 CN loss, TSC1 (negative regulator of mTOR) frameshift deletion mutation, and increased activation of mTOR, a serine/threonine kinase that governs metabolism, autophagy, and apoptosis. Increased mTOR was also associated with poor NPC prognosis. RESULTS: Everolimus, an mTOR inhibitor, suppressed tumor growth in the two PDX NPC models and had an additive antitumor effect with palbociclib, a CDK4/6 inhibitor. PDX tumors treated with various drugs or untreated were subjected to RNA sequencing, transcriptome profile analysis, and selective Western blotting to understand the interactions between these drugs and gene expression profiles. Palbociclib also suppressed EB viral nuclear antigen (EBNA1) expression in PDX-B13. Everolimus together with autophagy inhibitor, hydroxychloroquine, had additive anti-tumor effect on PDX-B13 tumor. Immunohistochemistry revealed that high mTOR levels were correlated with poor overall survival in patients with metastatic NPC (N = 90). CONCLUSIONS: High mTOR levels are a poor prognostic factor in NPC, and cell cycle, mTOR and autophagy pathways may serve as therapeutic targets in NPC. In addition, PDX models can be used for efficiently testing potential NPC drugs.

Identification of a Novel, Potent, and Orally Bioavailable Guanidine-Based SHP2 Allosteric Inhibitor from Virtual Screening and Rational Structural Optimization for the Treatment of KRAS Mutant Cancers.

Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) is a highly attractive therapeutic target for treating Kirsten rat sarcoma viral oncogene (KRAS) mutant cancers. In this work, a series of guanidine-based SHP2 allosteric inhibitors were discovered via virtual screening and rational structural optimization. Notably, lead compound 23 with potent SHP2 inhibitory activity (IC50 = 17.7 nM) effectively inhibited the proliferation, migration, and invasion of MIA PaCa-2 pancreatic cancer cells. Furthermore, compound 23 featured great in vivo pharmacokinetic properties (AUCpo = 4320 nM·h; F = 66.3%) and exhibited significant antitumor efficacy in the MIA PaCa-2 xenograft mouse model. This demonstrates that compound 23 is a potential lead compound for the development of SHP2 allosteric inhibitors to treat KRAS mutant cancers. Moreover, these guanidine-based scaffolds may provide an opportunity to mitigate the potential safety risks of the alkyl amine motif predominately incorporated in current SHP2 allosteric inhibitors.

Comprehensive assessment of pretreatment sarcopenia impacts on patients with EGFR-mutated NSCLC treated with afatinib.

BACKGROUND: This study aimed to comprehensively evaluate the efficacy and toxicity of afatinib in patients with sarcopenia, an important prognostic factor for treatment efficacy and toxicity in patients with cancer. METHODS: The clinical features of patients with advanced NSCLC treated with frontline afatinib between 2014 and 2018 at a medical center in Taiwan were retrospectively reviewed. Sarcopenia was evaluated based on the total cross-sectional area of skeletal muscles assessed by computed tomography (CT) imaging at the L3 level. Baseline characteristics, response rates, survival rates, and adverse events (AEs) were compared between sarcopenic and nonsarcopenic patients. RESULTS: A total of 176 patients evaluated for sarcopenia by CT and treated with afatinib were enrolled in the current study. Sarcopenia was significantly associated with good performance status, low body mass index (BMI), low body surface area (BSA), and low total mass area (TMA). Sarcopenia did not influence the response rate (69.2% vs. 72.0%, p = 0.299), progression-free survival (median 15.9 vs. 14.9 months, p = 0.791), or overall survival (median 26.5 vs. 27.2 months, p = 0.441). However, BSA ≤ 1.7 and the 40 mg afatinib dose were associated with dose reduction. TMA was the only independent factor for afatinib discontinuation due to AEs. CONCLUSION: Sarcopenia was not associated with treatment efficacy or toxicity among patients with NSCLC harboring common mutations treated with afatinib, indicating sarcopenic patients should not be excluded from afatinib treatment. Other factors, such as BSA and TMA, were associated with dose reduction and afatinib discontinuation, respectively, which may require additional evaluations in future studies.

Corrigendum: milR20 negatively regulates the development of fruit bodies in Pleurotus cornucopiae.

[This corrects the article DOI: 10.3389/fmicb.2023.1177820.].

Electrical Stability Modeling Based on Surface Potential for a-InGaZnO TFTs under Positive-Bias Stress and Light Illumination.

In this work, an electrical stability model based on surface potential is presented for amorphous In-Ga-Zn-O (a-IGZO) thin film transistors (TFTs) under positive-gate-bias stress (PBS) and light stress. In this model, the sub-gap density of states (DOSs) are depicted by exponential band tails and Gaussian deep states within the band gap of a-IGZO. Meanwhile, the surface potential solution is developed with the stretched exponential distribution relationship between the created defects and PBS time, and the Boltzmann distribution relationship between the generated traps and incident photon energy, respectively. The proposed model is verified using both the calculation results and experimental data of a-IGZO TFTs with various distribution of DOSs, and a consistent and accurate expression of the evolution of transfer curves is achieved under PBS and light illumination.

Cavitation bubble structures below a soft boundary in an ultrasonic field.

We studied the layer structure of bubbles just below water/air and water/EPE (Expand aple poly ephylene) interfaces using high-speed photography. The layer structure was generated by floating spherical clusters, the source bubbles of which were identified to come from the attachment of bubble nuclei at the interface, the floating of bubbles in the bulk liquid, or bubbles generated on the surface of the ultrasonic transducer. The boundary shape affected the layer structure, which assumed a similar profile below the water/EPE interface. We developed a simplified model composed of a bubble column and bubble chain to describe interface impacts and the interaction of bubbles in a typical branching structure. We found that the resonant frequency of the bubbles is smaller than that of an isolated single bubble. Moreover, the primary acoustic field plays an important role in the generation of the structure. A higher acoustic frequency and pressure were found to shorten the distance between the structure and the interface. A hat-like layer structure of bubbles was more likely to exist in the low-frequency (28 and 40 kHz) intense inertial cavitation field, in which bubbles oscillate violently. By contrast, structures composed of discrete spherical clusters were more likely to form in the relatively weak cavitation field at 80 kHz, in which stable and inertial cavitation coexisted. The theoretical predictions were in good agreement with the experimental observations.

The relationship between dominant follicle development and clinical outcomes of hormone replacement therapy-frozen embryo transfer: a retrospective clinical study.

Research question: Hormone replacement therapy (HRT) is one of the most used endometrial preparation protocols for frozen embryo transfer (FET) due to the convenience of its administration and stability of pregnancy outcomes. There are several HRT cycles accompanied by the development of dominant follicles. However, the relationship between dominant follicle development and clinical outcomes in HRT-FET cycles remains unclear. Design: We carried out a retrospective cohort study of 13251 cycles at our reproductive medicine center from 2012 to 2019. Total cycles were divided into two groups according to whether there was dominant follicular development. In addition, we conducted a secondary analysis that used propensity-score matching to reduce confounding variables. A univariate and multivariable logistic regression model was further employed to analyze the effect of dominant follicle development in HRT cycles on clinical pregnancy outcomes. Results: There was no significant correlation between dominant follicle development in HRT-FET cycles and the clinical pregnancy rate (adjusted OR = 1.162, 95% CI: 0.737-1.832, P = 0.52). In addition, there was a positive correlation between the basic follicle-stimulating hormone (FSH) level and the development of dominant follicles, while there was a negative correlation between antral follicle count (AFC), menstrual cycle length and the development of dominant follicles in HRT cycles. Conclusions: The development of dominant follicles in HRT-FET cycles does not affect the clinical pregnancy rate, early miscarriage rate and live birth rate. Therefore, it is not necessary to immediately cancel the FET cycle immediately when dominant follicle development is monitored in the HRT-FET cycle.

PGC7 regulates H3K27me3 modification by inhibiting the interaction of YY1 with PRC2.

Primordial germ cell 7 (PGC7)(Dppa3 or Stella) is a small inherently disordered protein that is mainly expressed in oocytes and plays a vital role in the regulation of DNA methylation reprogramming in imprinted loci through interaction with other proteins. Most of PGC7-deficient zygotes are blocked at two-cell stage with an increased tri-methylation at lysine 27 of histone H3 (H3K27me3) level in the nucleus. Our previous work has indicated that PGC7 interacts with yin-yang1 (YY1) that is essential for the recruitment of enhancer of zeste homolog 2 (EZH2)-containing Polycomb repressive complex 2 (PRC2) to H3K27me3 modification sites. Here, we found that the presence of PGC7 weakened the interaction between YY1 and PRC2 without disrupting the assembly of core subunits of the PRC2 complex. In addition, PGC7 promoted AKT to phosphorylate serine 21 of EZH2, resulting in inhibition of EZH2 activity and the dissociation of EZH2 from YY1, thereby decreasing H3K27me3 level. In zygotes, the PGC7-deficient and AKT inhibitor MK2206 both promoted EZH2 to enter the pronuclei but without disturbing the subcellular localization of YY1 and caused an increase in the level of H3K27me3 in the pronuclei, as well as inhibition of the expression of zygote-activating genes regulated by H3K27me3 in two-cell embryos. In summary, PGC7 could affect zygotic genome activation during early embryonic development by regulating the level of H3K27me3 through regulation of PRC2 recruitment, EZH2 activity, and subcellular localization.NEW & NOTEWORTHY PGC7 and YY1 interaction inhibits recruitment of PRC2 by YY1. PGC7 promotes AKT and EZH2 interaction to increase pEZH2-S21 level, which weakens YY1 and EZH2 interaction, thereby decreasing H3K27me3 level. In zygotes, the PGC7-deficient and AKT inhibitor MK2206 promote EZH2 to enter the pronuclei, and increase H3K27me3 level in the pronuclei, as well as inhibition of the expression of zygote-activating genes regulated by H3K27me3 in two-cell embryos, which ultimately affects early embryo development.