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Abstract Background Oocyte maturation defect (OMD) and early embryonic arrest result in female infertility. Previous studies have linked biallelic mutations in the PATL2 gene to OMD, yet the underlying mechanism remains largely unknown. Results This study uncovers three novel mutations (c.1201G > T, c.1284delA and c.1613 + 2_1613 + 3insGT) and three reported mutations (c.1204 C > T, c.1271T > C, c.223 − 14_223-2delCCCTCCTGTTCCA) in the PATL2 gene across five unrelated individuals exhibiting OMD, oocyte death, and early embryonic arrest. RNA sequencing revealed that PATL2 mutations decreased mRNA storage in human germinal vesicle (GV) oocytes and impeded mRNA decay during maturation and in early embryos. We demonstrate that PATL2 interacts with CPEB1 and TUT7 in human oocytes to maintain mRNA homeostasis. Additionally, we observed a reduction in CCNB1 and CCNE1 mRNA levels in PATL2-mutant GV oocytes, which may be linked to GV arrest. Employing both wild-type and mutated PATL2V401F/R402W variants, we characterized the protein interactome of PATL2, identifying disruptions of PATL2V401F/R402W variants predominantly affecting cell cycle-related proteins, including CDC23, APC1 and MAD2L1. PATL2’s interaction with and stabilization of CDC23 in oocytes may elucidate the mechanisms behind the mutation-induced MI arrest. PALT2 is required for the efficient mRNA translation and it maintains the protein level of CDC23, APC1 and MAD2L1 in mouse GV oocyte. Conclusion PATL2 plays a critical role in regulating mRNA accumulation and decay in human oocytes, potentially through interactions with CPEB1 and TUT7, respectively. Mutations in PATL2 lead to oocyte meiosis defects by affecting the mRNA accumulation, mRNA translation, and direct binding to and stabilizing proteins related to cell cycle regulation, such as CCNB1 and CDC23. This study expands the mutational spectrum of PATL2 and provides new insights into the molecular mechanisms underlying PATL2 mutation-associated oocyte maturation disorders.

Abstract Background Acupuncture is an effective complementary therapy for nausea and vomiting during pregnancy (NVP). Nevertheless, the utilization of acupuncture for NVP has been minimally explored in current scholarly research, with a paucity of systematic randomized clinical trials (RCTs) in it. We aim to evaluate the effects of acupuncture on NVP after assisted reproductive techniques (ART) and explore the metabolism-related mechanism of the efficacy. Methods This single-blind, randomized, controlled trial will randomize 68 patients with NVP after ART to a traditional acupuncture (tACP) or a sham acupuncture (sACP) group. The tACP group will receive tACP thrice a week for 2 weeks with a day interval between sessions, while the sACP group will undergo the same number of nonpenetrative acupuncture at non-acupoints for the same period. Pregnancy-specific quantification of emesis will be used to evaluate symptom severity. Routine blood and urine tests, liver and kidney function tests, human chorionic gonadotropin, nuchal translucency thickness, and embryonic development measured using ultrasound will be used to evaluate safety during pregnancy. Non-targeted metabolomic analysis will be performed to explore the association between metabolic changes and clinical symptoms. Discussion This study will elucidate the effects and safety of acupuncture in treating NVP in women undergoing ART. The results of this study will contribute to optimizing acupuncture therapies by combining the body and auricular points and exploring the underlying therapeutic mechanism using a metabolomics approach. Trial registration Chinese Clinical Trial Registry, ChiCTR2300075259.

Abstract Background Transcervical resection of adhesions (TCRA) is the standard treatment for intrauterine adhesion (IUA). Previous studies have shown that postoperative oral estrogen or an intrauterine physical barrier could reduce the recurrence of IUA by promoting the proliferation of the endometrium or inhibiting the reformation of adhesions. Our team designed an intrauterine stent that can release estrogen within the uterine cavity slowly. In this study, we aimed to investigate the efficacy and safety of the estrogen-releasing intrauterine system in preventing the recurrence of moderate to severe IUA. Methods This was a multicenter prospective randomized controlled 2-arm parallel trial that included patients who were diagnosed with moderate to severe IUA and who received TCRA. A total of 250 patients were randomly assigned, at a 1:1 ratio, to receive the intrauterine estrogen-releasing system or a Foley catheter balloon combined with oral estrogen therapy after surgery. The primary outcome was the rate of adhesion reduction in the two groups. The secondary outcomes included endometrial thickness at the ovulation period, menstrual improvement rates, and other reported adverse events during follow-up. Results The average daily drug release amount for all the tested stents was 0.21 mg/day. At 60 days postoperatively, the rate of adhesion reduction was significantly greater in the experimental group than in the control group (93.33% vs. 58.56%, p

Abstract Background The monthly regeneration of human endometrial tissue is maintained by the presence of human endometrial mesenchymal stromal/stem cells (eMSC), a cell population co-expressing the perivascular markers CD140b and CD146. Endometrial regeneration is impaired in the presence of intrauterine adhesions, leading to infertility, recurrent pregnancy loss and placental abnormalities. Several types of somatic stem cells have been used to repair the damaged endometrium in animal models, reporting successful pregnancy. However, the ability of endometrial stem cells to repair the damaged endometrium remains unknown. Methods Electrocoagulation was applied to the left uterine horn of NOD/SCID mice causing endometrial injury. Human eMSC or PBS was then injected into the left injured horn while the right normal horn served as controls. Mice were sacrificed at different timepoints (Day 3, 7 and 14) and the endometrial morphological changes as well as the degree of endometrial injury and repair were observed by histological staining. Gene expression of various inflammatory markers was assessed using qPCR. The functionality of the repaired endometrium was evaluated by fertility test. Results Human eMSC successfully incorporated into the injured uterine horn, which displayed significant morphological restoration. Also, endometrium in the eMSC group showed better cell proliferation and glands formation than the PBS group. Although the number of blood vessels were similar between the two groups, gene expression of VEGF-α significantly increased in the eMSC group. Moreover, eMSC had a positive impact on the regeneration of both stromal and epithelial components of the mouse endometrium, indicated by significantly higher vimentin and CK19 protein expression. Reduced endometrial fibrosis and down-regulation of fibrosis markers were also observed in the eMSC group. The eMSC group had a significantly higher gene expression of anti-inflammatory factor Il-10 and lower mRNA level of pro-inflammatory factors Ifng and Il-2, indicating the role of eMSC in regulation of inflammatory reactions. The eMSC group showed higher implantation sites than the PBS group, suggesting better endometrial receptivity with the presence of newly emerged endometrial lining. Conclusions Our findings suggest eMSC improves regeneration of injured endometrium in mice.

Objective: To compare the reproductive pregnancy outcomes of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) plus hormone replacement therapy (HRT) with HRT-only cycles, and investigate differences between single polypectomy and multiple polypectomies, and between one or two doses of GnRH-a. Materials and methods: This was a retrospective cohort study on patients undergoing polypectomy who underwent frozen–thawed embryo transfer (FET) from March 2018 to May 2019. They were divided into GnRH-a pretreatment and HRT-only groups. Each group was divided into single polypectomy or multiple polypectomies (in a single hysteroscopic session) subgroups. Clinical pregnancy rate and live birth rate (LBR) were the main outcomes. The effect of GnRH-a dosage was further analysed. Results: There were 212 GnRH-a pretreatment cases (45 single and 167 multiple polyps) and 448 HRT-only cases (228 single and 220 multiple polyps). The LBR of the GnRH-a pretreatment group (53.3%) was significantly higher than the HRT group (43.3%; P = 0.016). Logistic regression analysis showed that GnRH-a pretreatment significantly affected the LBR (odds ratio, OR 1.470, 95% confidence interval, Cl 1.046–2.065; P = 0.026). In the multiple polypectomy subgroup, the LBR with GnRH-a pretreatment was higher than with HRT-only (54.5% vs 43.6%; P = 0.034). However, the LBR was not different between the respective single polypectomy subgroups (48.9% vs 43.0%; P = 0.466). For patients with multiple polyps, two GnRH-a pretreatments produced a higher LBR than a single GnRH-a pretreatment (62.7% vs 47.8%), but without significant difference (P = 0.055). Conclusion: GnRH-a pretreatment improved the LBR for FET cycles after hysteroscopic multiple polypectomies, independent of dose.

Abstract Chemotherapy-induced ovarian damage and infertility are significant concerns for women of childbearing age with cancer; however, the underlying mechanisms are still not fully understood. Our study has revealed a close association between epigenetic regulation and cyclophosphamide (CTX)-induced ovarian damage. Specifically, CTX and its active metabolite 4-hydroperoxy cyclophosphamide (4-HC) were found to increase the apoptosis of granulosa cells (GCs) by reducing EZH2 and H3K27me3 levels, both in vivo and in vitro. Furthermore, RNA-seq and CUT&Tag analyses revealed that the loss of H3K27me3 peaks on promoters led to the overactivation of genes associated with transcriptional regulation and apoptosis, indicating that stable H3K27me3 status could help to provide a safeguard against CTX-induced ovarian damage. Administration of the H3K27me3-demethylase inhibitor, GSK-J4, prior to CTX treatment could partially mitigate GC apoptosis by reversing the reduction of H3K27me3 and the aberrant upregulation of specific genes involved in transcriptional regulation and apoptosis. GSK-J4 could thus potentially be a protective agent for female fertility when undergoing chemotherapy. The results provide new insights into the mechanisms for chemotherapy injury and future clinical interventions for fertility preservation.

Abstract To evaluate the association between the number of oocytes retrieved and cumulative live birth rate (CLBR) in different female age strata. 17,931 women undergoing their first IVF/ICSI-ET cycle in the Sir Run Run Shaw Hospital of Zhejiang University were grouped by age (A: ≤ 35 years; B: ≥ 36 years) as well as the number of oocytes retrieved (a: ≤ 5; b:6–9; c:10–14; d: ≥ 15). Multivariate regression analysis was performed to assess the OR of CLBR for the variable ‘age’ and ‘number of oocytes retrieved’. The group ≥ 36 years exhibited lower cumulative pregnancy rates (CPRs) and cumulative live birth rates (CLBRs), which are proportional to the number of oocytes retrieved but opposite to increasing age. Multivariate logistic regression analysis revealed that the age and number of oocytes retrieved remain significant independent predictive factors (P

Due to the physiological alteration during pregnancy, maternal gut microbiota changes following the metabolic processes. Recent studies have revealed that maternal gut microbiota is closely associated with the immune microenvironment in utero during pregnancy and plays a vital role in specific pregnancy complications, including preeclampsia, gestational diabetes, preterm birth and recurrent miscarriages. Some other evidence has also shown that aberrant maternal gut microbiota increases the risk of various diseases in the offspring, such as allergic and neurodevelopmental disorders, through the immune alignment between mother and fetus and the possible intrauterine microbiota. Probiotics and the high-fiber diet are effective inventions to prevent mothers and fetuses from diseases. In this review, we summarize the role of maternal gut microbiota in the development of pregnancy complications and the health condition of future generations from the perspective of immunology, which may provide new therapeutic strategies for the health management of mothers and offspring.

Abstract Defective decidualization of endometrial stromal cells (ESCs) in endometriosis (EM) patients leads to inadequate endometrial receptivity and EM‐associated infertility. Hypoxia is an inevitable pathological process of EM and participates in deficient decidualization of the eutopic secretory endometrium. Enhancer of zeste homology 2 (EZH2) is a methyltransferase which catalyses H3K27Me3, leading to decreased expression levels of target genes. Although EZH2 expression is low under normal decidualization, it is abundantly increased in the eutopic secretory endometrium of EM and is induced by hypoxia. Chromatin immunoprecipitation‐PCR results revealed that decidua marker IGFBP1 is a direct target of EZH2, partially explaining the increased levels of histone methylation modification in defected decidualization of EM. To mechanism controlling this, we examined the effects of hypoxia on EZH2 and decidualization. EZH2 mRNA showed decreased m6A modification and increased expression levels under hypoxia and decidualization combined treatment. Increased EZH2 expression was due to the increased expression of m6A demethylase ALKBH5 and decreased expression of the m6A reader protein YTHDF2. YTHDF2 directly bind to the m6A modification site of EZH2 to promote EZH2 mRNA degradation in ESCs. Moreover, selective Ezh2 depletion in mouse ESCs increased endometrial receptivity and improved mouse fertility by up‐regulating decidua marker IGFBP1 expression. This is the first report showing that YTHDF2 can act as a m6A reader to promote decidualization by decreasing the stability of EZH2 mRNA and further increasing the expression of IGFBP1 in ESCs. Taken together, our findings highlight the critical role of EZH2/H3K27Me3 in decidualization and reveal a novel epigenetic mechanism by which hypoxia can suppress EM decidualization by decreasing the m6A modification of EZH2 mRNA.

The development of the cerebral cortex during the fetal period is a complex yet well-coordinated process. MRI-based morphological brain network provides a powerful tool for describing this process at a network level. Due to the challenges of in-utero MRI acquisition and image processing, the fetal morphological brain network has not been established. In this study, utilizing high-resolution in-utero MRI data, we constructed an individual morphometric similarity network for each fetus based on multiple cortical features. The spatiotemporal development of morphological connections was described at the level of edge, node, and lobe, respectively. Based on graph theoretical method, the topology structure of fetal morphological network was characterized. Edge analysis demonstrated an increase of morphological dissimilarity between hemispheres with gestational age, especially for the parietal cortex. The limbic and parieto-occipital regions exhibited the most drastic changes of morphological connections at both the edge and node levels. Between- and within-lobe analysis illustrated that the limbic lobe became more similar to other lobes, while the parietal and occipital lobes became more dissimilar to other lobes. Graph theoretical analysis indicated that the small-world structure of the fetal morphological network appeared as early as 22 weeks and that the network topology exhibited an enhanced integration and reduced segregation during prenatal development. The findings obtained from the preterm-born neonates agreed well with those of the fetuses. In summary, this study fills a gap in prenatal morphological brain network research and provides a piece of important evidence for understanding the normal development of fetal brain connectome during the second-third trimester.

Endometrium is suspectable to severe injury due to recurrent abortion, curettage or intrauterine infection which could lead to pathological conditions and sabotage women's fertility. Promoting endometrium regeneration is the core of the treatments to uterine related infertility. Patients who received traditional treatments can only expect limited effects, thereby novel therapies are badly in need to promote endometrium regeneration. Here we generated a decellularized extracellular matrix (ECM) from porcine dermis, and composited adipose stem cell derived exosomes (ADSC-exos) on it (ECM@ADSC-exos). In vitro experiments proved that ECM@ADSC-exos exhibited good cytocompatibility and could improve cell proliferation, migration and angiogenesis. We also observed that, when implanted in the uterine cavity of a rat model of endometrium injury, ECM@ADSC-exos improved endometrium regeneration, enhanced local angiogenesis, promoted myometrium repair and finally preserved fertility. Our results proved that ECM@ADSC-exos could be a novel option for endometrium regeneration.

Abstract Background Epigenetic reprogramming is involved in luteinizing hormone (LH)-induced ovulation; however, the underlying mechanisms are largely unknown. Results We here observed a rapid histone deacetylation process between two waves of active transcription mediated by the follicle-stimulating hormone (FSH) and the LH congener human chorionic gonadotropin (hCG), respectively. Analysis of the genome-wide H3K27Ac distribution in hCG-treated granulosa cells revealed that a rapid wave of genome-wide histone deacetylation remodels the chromatin, followed by the establishment of specific histone acetylation for ovulation. HDAC2 phosphorylation activation coincides with histone deacetylation in mouse preovulatory follicles. When HDAC2 was silenced or inhibited, histone acetylation was retained, leading to reduced gene transcription, retarded cumulus expansion, and ovulation defect. HDAC2 phosphorylation was associated with CK2α nuclear translocation, and inhibition of CK2α attenuated HDAC2 phosphorylation, retarded H3K27 deacetylation, and inactivated the ERK1/2 signaling cascade. Conclusions This study demonstrates that the ovulatory signal erases histone acetylation through activation of CK2α-mediated HDAC2 phosphorylation in granulosa cells, which is an essential prerequisite for subsequent successful ovulation.

Rudimentary horn of the uterus is a rare congenital malformation that is characterized by significant anatomic variability. We report two cases involving women who presented with a broadly attached rudimentary horn and large ovarian endometriomas that were innovatively treated by laparoscopic coring-type dissection of the rudimentary horn of the uterus. This novel surgical approach ensured the integrity of the myometrium of the unicornuate uterus and avoided uterine rupture during pregnancy and ipsilateral ovarian function impairment.

Sepsis is a life-threatening condition, especially in very low birth weight (VLBW) infants, and its pathogenesis remains unclear. Effective biomarkers need to be found to diagnose and treat the disease at an early stage. The Gene Expression Omnibus (GEO) database was screened and analyzed for differentially expressed genes (DEGs) in VLBW infants with sepsis. DEGs were then analyzed for functional enrichment. A weighted gene co-expression network analysis (WCGNA) was performed to identify the key modules and genes. The optimal feature genes (OFGs) were created using three machine learning algorithms. The single-sample Gene Set Enrichment Analysis (ssGSEA) scored the degree of immune cell enrichment between septic and control patients, and the correlation between OFGs and immune cells was evaluated. A total of 101 DEGs were identified between the sepsis and control samples. DEGs were mainly associated with immune responses and inflammatory signaling pathways in the enrichment analysis. In the WGCNA analysis, the MEturquoise module was significantly correlated with sepsis in VLBW infants (cor = 0.57, P < 0.001). By intersecting OFGs derived from three machine learning algorithms, two biomarkers were identified: glycogenin 1 (GYG1) and resistin (RETN). The area under the curves of GYG1 and RETN was greater than 0.97 in the testing set. The ssGSEA indicated immune cells infiltration in septic VLBW infants, and GYG1 and RETN revealed close correlations with immune cells. New biomarkers offer promising insights into the diagnosis and treatment of sepsis in VLBW infants.

Objective: This study aims to evaluate the surgical morbidity and obstetric outcomes following in-pregnancy or pre-pregnancy laparoscopic abdominal cerclage (LAC) for patients who were diagnosed with refractory cervical insufficiency or had a short cervix. Methods: A retrospective study was conducted on patients undergoing LAC between May 2017 and May 2019 at the Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital. The patients were diagnosed with refractory cervical insufficiency based upon a previous failed transvaginal cervical cerclage (TVC), or had a short cervix who were considered unsuitable for a TVC after a previous cervical procedure. All patients were followed-up after surgery with transperineal ultrasonography until May 2020. Subsequently, surgical and obstetric data were collected and analyzed. Results: In total, 44 patients underwent LAC, with 8 patients in-pregnancy and 36 pre-pregnancy. For the patient with pre-pregancy LAC, the pregnancy rate was 80.6% (29/36), including 3 patients with first-trimester loss, 1 patient with an ectopic pregnancy, and 25 patients with a delivery. For the remaining 7 patients, 3 did not conceive, and another 4 had no pregnancy plans. All the patients with in-pregnancy LAC had a delivery. The “take-home baby” rate was 89.2% (33/37), with a live-birth rate of 100% and a neonatal survival rate of 100% for both patients with in-pregnancy and pre-pregnancy LAC. For patients with in-pregnancy LAC, 75.0% (6/8) patients delivered at ≥37 wk of gestation, 12.5% (1/8) delivered between 34 and 36+6 wk, and 12.5% (1/8) delivered between 28 and 33+6 wk. For patients with pre-pregnancy LAC, 80.0% (20/25) patients delivered at ≥37 wk of gestation, 16.0% (4/25) delivered between 34 and 36+6 wk, and 4.0% (1/25) delivered between 28 and 33+6 wk. No adverse-event intra-operative or post-operative sequelae were noted. Conclusions: LAC is an effective and safe procedure that results in remarkable obstetric outcomes for women with refractory cervical insufficiency, or with a short cervix who are considered unsuitable for a TVC. The success rate of in-pregnancy or pre-pregnancy LAC depends on a full evaluation of patients, a proper peri-operative management and close follow-up.

BackgroundThis study aims to evaluate the value of the proportion of large platelets (PLCR) and platelet crit (PCT) in predicting necrotizing enterocolitis (NEC) in low birth weight (LBW) neonates.MethodsA total of 155 LBW (

Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions (IUAs). Evidence shows that apoptosis occurs in a majority of grafted stem cells, and apoptotic bodies (ABs) play a critical role in compensatory tissue regeneration. However, the therapeutic potential of AB-based therapy and its mechanism have not been explored in detail. Here, a cell-free therapeutic strategy was developed by incorporating mesenchymal stem cell-derived ABs into a hyaluronic acid (HA) hydrogel to achieve endometrial regeneration and fertility restoration. Specifically, we found that the ABs could induce macrophage immunomodulation, cell proliferation, and angiogenesis in vitro. The HA hydrogel promoted the retention of ABs and facilitated their continuous release. In a murine model of acute endometrial damage and a rat model of IUAs, in situ injection of the AB-laden HA hydrogel could efficiently reduce fibrosis and promote endometrial regeneration, resulting in the fertility restoration. Consequently, ABs show good potential as therapeutic vesicles, and the AB-laden HA hydrogel appears to be a clinically feasible and cell-free alternative for endometrial regeneration and IUA treatment.

Background and Aims: To verify whether endometrial scratch in mid-luteal phase affect the genomic characteristics of peri-implantation endometrium in the following cycle. Method: A Retrospectively self-control cohort study was conducted in a university assisted reproductive unit. A total of eight women with recurrent implantation failure were included. Each participant had endometrial biopsy twice, one biopsy was done on day LH+7 in a natural cycle, and the second biopsy was performed on day LH+7 of the following cycle. R package was used for identifying differentially expressed genes between the first biopsy group and the second biopsy group, and for gene set enrichment analysis. Results: The paired sample showed no significant difference in gene expression profiles of endometrium before and after endometrial scratch. Conclusion: It suggests that endometrial scratch performed during previous mid-luteal phase did not affect the genomic profiles of endometrium on day LH+7 in women with recurrent implantation failure.

Abstract We aimed to investigate the difference in the time to pregnancy (TTP) between women with previous ectopic pregnancy (EP) and control women following in vitro fertilization (IVF) treatment and the association between TTP and the number of oocytes retrieved and embryos available. A retrospective study involving 1097 women, 547 of which had previous EP and 550 were control women whose previous pregnancy were abortion, was conducted. Women in the EP group had significantly longer median TTP than those in the control group (36; range, 12–252 vs 28; range, 12–220; P = 0.019). For women with previous EP, > 48 months TTP was most likely associated with low numbers of oocytes retrieved and embryos available compared to TTP of ≤ 24 months or 25–48 months, and women with younger age had a shorter TTP, higher numbers of oocytes retrieved and embryos available. A Cox proportional hazards model showed that maternal age was significantly related to the pregnancy over the TTP (adjusted hazard ratio, 0.934; P

Placental dysfunction refers to the insufficiency of placental perfusion and chronic hypoxia during early pregnancy, which impairs placental function and causes inadequate supply of oxygen and nutrients to the fetus, affecting fetal development and health. Fetal intrauterine growth restriction, one of the most common outcomes of pregnancy-induced hypertensions, can be caused by placental dysfunction, resulting from deficient trophoblast syncytialization, inadequate trophoblast invasion and impaired vascular remodeling. During placental development, cytotrophoblasts fuse to form a multinucleated syncytia barrier, which supplies oxygen and nutrients to meet the metabolic demands for fetal growth. A reduction in the cell fusion index and the number of nuclei in the syncytiotrophoblast are found in the placentas of pregnancies complicated by IUGR, suggesting that the occurrence of IUGR may be related to inadequate trophoblast syncytialization. During the multiple processes of trophoblasts syncytialization, specific proteins and several signaling pathways are involved in coordinating these events and regulating placental function. In addition, epigenetic modifications, cell metabolism, senescence, and autophagy are also involved. Study findings have indicated several abnormally expressed syncytialization-related proteins and signaling pathways in the placentas of pregnancies complicated by IUGR, suggesting that these elements may play a crucial role in the occurrence of IUGR. In this review, we discuss the regulators of trophoblast syncytialization and their abnormal expression in the placentas of pregnancies complicated by IUGR.

Objective As one of the most common endocrine disorders in women of reproductive age, polycystic ovary syndrome (PCOS) is highly heterogeneous with varied clinical features and diverse gestational complications among individuals. The patients with PCOS have 2-fold higher risk of preterm labor which is associated with substantial infant morbidity and mortality and great socioeconomic cost. The study was designated to identify molecular subtypes and the related hub genes to facilitate the susceptibility assessment of preterm labor in women with PCOS. Methods Four mRNA datasets (GSE84958, GSE5090, GSE43264 and GSE98421) were obtained from Gene Expression Omnibus database. Twenty-eight candidate genes related to preterm labor or labor were yielded from the researches and our unpublished data. Then, we utilized unsupervised clustering to identify molecular subtypes in PCOS based on the expression of above candidate genes. Key modules were generated with weighted gene co-expression network analysis R package, and their hub genes were generated with CytoHubba. The probable biological function and mechanism were explored through Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. In addition, STRING and Cytoscape software were used to identify the protein-protein interaction (PPI) network, and the molecular complex detection (MCODE) was used to identify the hub genes. Then the overlapping hub genes were predicted. Results Two molecular subtypes were found in women with PCOS based on the expression similarity of preterm labor or labor-related genes, in which two modules were highlighted. The key modules and PPI network have five overlapping five hub genes, two of which, GTF2F2 and MYO6 gene, were further confirmed by the comparison between clustering subgroups according to the expression of hub genes. Conclusions Distinct PCOS molecular subtypes were identified with preterm labor or labor-related genes, which might uncover the potential mechanism underlying heterogeneity of clinical pregnancy complications in women with PCOS.

We present the porcine skin ablation using a mid-infrared high-repetition-rate picosecond pulse burst laser. A burst-mode pulse with a repetition rate of 16.32 MHz was generated from a home-built difference frequency generation (DFG) system operating at 3 μm. Within each burst, there were 16 equally spaced 8.5 ps sub-pulses at an intra-burst repetition rate of ∼3.3 GHz. To study the laser-tissue interaction, laser powers of 1 to 2 W, and scanning times from 1 to 10 with spot size of ∼50 μm were applied to irradiate the fresh porcine skin. The results demonstrate that the burst-mode pulse with modest peak power density of MW/cm2 is efficient for tissue ablation. The optimized ablation depth increased with the average power and scanning times, reaching a maximal incision depth of 150 μm. Thanks to the high repetition rate of intra-burst pulse and high absorption of radiation, the ablation width and thermal effect width kept within 50 μm and 25 μm in all control groups. It is believed that as the first demonstration, such mid-infrared burst-mode laser radiation with modest power intensity is of great potential to realize micron penetration depth and low thermal effect in high-precision surgery applications.

Recurrent pregnancy loss (RPL) is a severe complication of pregnancy that is caused by genetic abnormalities, immune dysfunction, aberrant cell biology, and tissue structure destruction. Among which, placental dysfunction is crucial in the pathogenetic progression of RPL. Although some regulatory factors associated with RPL have been reported, the placental changes correlated with RPL still need to be elucidated. Here, we found that a portion of RPL patients presented with low serum and placental S100P expression. Using a human trophoblast stem cell model, we demonstrated that S100P was exclusively expressed in syncytiotrophoblast (ST)-like syncytia (ST(2D)-TSCT) and that loss of S100P expression in ST(2D)-TSCT cells impaired β-hCG secretion, leading to syncytialization failure during early placental development. Moreover, we found that S100P is involved in regulating trophoblast syncytialization by downregulating the protein level of Yes-associated protein 1 (YAP1), which plays a pivotal role in maintaining trophoblast stemness. Together, our findings suggest that S100P plays an essential role in regulating trophoblast syncytialization during early placental development in humans via YAP1. Additionally, lower serum S100P levels may predict poor pregnancy outcomes and represent a potentially useful marker for evaluating placental biological function during early pregnancy.

The disease neonatal sepsis (NS) poses a serious threat to life, and its pathogenesis remains unclear. Using the Gene Expression Omnibus (GEO) database, differentially expressed genes (DEGs) were identified and functional enrichment analyses were conducted. Three machine learning algorithms containing the least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF) were applied to identify the optimal feature genes (OFGs). This study conducted CIBERSORT to present the abundance of immune infiltrates between septic and control neonates and assessed the relationship between OFGs and immune cells. In total, 44 DEGs were discovered between the septic and control newborns. Throughout the enrichment analysis, DEGs were primarily related to inflammatory signaling pathways and immune responses. The OFGs derived from machine learning algorithms were intersected to yield four biomarkers, namely Hexokinase 3 (HK3), Cystatin 7 (CST7), Resistin (RETN), and Glycogenin 1 (GYG1). The potential biomarkers were validated in other datasets and LPS-stimulated HEUVCs. Septic infants showed a higher proportion of neutrophils (p < 0.001), M0 macrophages (p < 0.001), and regulatory T cells (p = 0.004). HK3, CST7, RETN, and GYG1 showed significant correlations with immune cells. Overall, the biomarkers offered promising insights into the molecular mechanisms of immune regulation for the prediction and treatment of NS.

Abstract Accumulating evidences shed light on the important roles of Circular RNAs (circRNAs) acting as competing endogenous RNAs (ceRNAs) in cervical cancer (CC) biology. The present study aimed to identify a novel circRNA-related prognostic signature for CC. The expression data and clinical information of CC were downloaded from the Gene Expression Omnibus (GEO) datasets to identify the differential circRNAs expression. Based on the targeted miRNA prediction, circRNA-related miRNAs were detected in training group and validation group of The Cancer Genome Atlas (TCGA) dataset to construct the novel prognostic signature of CC with least absolute shrinkage and selection operator (LASSO). Moreover, the Kaplan-Meier (K-M) analysis was applied to test the model. In the present study, three differentially expressed circRNAs (hsa_circ_0001498, hsa_circ_0066147, and hsa_circ_0006948) were identified in GSE102686 and GSE107472. Then, with the criteria 25 predicted miRNAs were analyzed in TCGA datasets to calculate the prognostic signature. Furthermore, we developed a six-miRNA signature (hsa-miR-217, hsa-miR-30b-3p, hsa-miR-136-5p, hsa-miR-185-3p, hsa-miR-501-5p and hsa-miR-658) based on their expression level and coefficients. We performed a Pearson correlation analysis to screen 47 mRNAs which are negatively regulated by these six miRNAs. Functional enrichment analysis indicated these mRNAs were mainly enriched in cancer-related biology, such as regulation of transcription, signal transduction, and cell cycle. The present study provides novel insight for better understanding of circRNA-related ceRNA network in CC and facilitates the identification of potential biomarkers for prognosis.

The outcomes of in vitro fertilization (IVF) for endometriotic women are significantly worse than for patients without ovarian endometriosis (OEM), as shown by fewer retrieved oocytes. However, the exact pathophysiological mechanism is still unknown. Thus, we conducted a prospective study that analyzed mRNA and lncRNA transcriptome between granulosa cells (GCs) from patients with fewer retrieved oocytes due to OEM and GCs from controls with male factor (MF) infertility using an RNA sequencing approach. We found a group of significantly differentially expressed genes (DEGs), including NR5A2, MAP3K5, PGRMC2, PRKAR2A, DEPTOR, ITGAV, KPNB1, GPC6, EIF3A, and SMC5, which were validated to be upregulated and negatively correlated with retrieved oocyte numbers in GCs of patients with OEM, while DUSP1 demonstrated the opposite. The molecular functions of these DEGs were mainly enriched in pathways involving mitogen-activated protein kinase (MAPK) signaling, Wnt signaling, steroid hormone response, apoptosis, and cell junction. Furthermore, we performed lncRNA analysis and identified a group of differentially expressed known/novel lncRNAs that were co-expressed with the validated DEGs and correlated with retrieved oocyte numbers. Co-expression networks were constructed between the DEGs and known/novel lncRNAs. These distinctive molecular signatures uncovered in this study are involved in the pathological regulation of ovarian reserve dysfunction in OEM patients.