Novel Splicing Variants in the ARR3 Gene Cause the Female-Limited Early-Onset High Myopia.

Purpose: Variants in the ARR3 gene have been linked to early-onset high myopia (eoHM) with a unique X-linked female-limited inheritance. However, the clinical validity of this gene-disease association has not been systematically evaluated. Methods: We identified two Chinese families with novel ARR3 splicing variants associated with eoHM. Minigene constructs were generated to assess the effects of the variants on splicing. We integrated previous evidence to curate the clinical validity of ARR3 and eoHM using the ClinGen framework. Results: The variants c.39+1G>A and c.100+4A>G were identified in the two families. Minigene analysis showed both variants resulted in abnormal splicing and introduction of premature termination codons. Based on genetic and experimental evidence, the ARR3-eoHM relationship was classified as "definitive." Conclusions: Our study identified two novel splicing variants of the ARR3 gene linked to eoHM and confirmed their functional validity via minigene assay. This research expanded the mutational spectrum of ARR3 and confirmed the minigene assay technique as an effective tool for understanding variant effects on splicing mechanisms.

The involvement of RNA N6-methyladenosine and histone methylation modification in decidualization and endometriosis-associated infertility.

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 m6 A modification and increased expression levels under hypoxia and decidualization combined treatment. Increased EZH2 expression was due to the increased expression of m6 A demethylase ALKBH5 and decreased expression of the m6 A reader protein YTHDF2. YTHDF2 directly bind to the m6 A 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 m6 A 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 m6 A modification of EZH2 mRNA.

ADSC-derived exosomes-coupled decellularized matrix for endometrial regeneration and fertility restoration.

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.

Damage Model of Steel Fiber-Reinforced Coal Gangue Concrete under Freeze-Thaw Cycles Based on Weibull Distribution.

In order to improve the utilization rate of coal gangue and expand the application range of coal gangue concrete (CGC), a certain proportion of steel fiber was added to the concrete, and the freeze-thaw cycles (FTCs) and flexural tests were used to explore the effects of different mass replacement rates of coal gangue (0%, 25%, 50%, 75%, and 100%) and different proportions of the volumetric blending of the steel fiber (0%, 0.8%, 1.0%, and 1.2%) on the frost resistance of steel fiber-reinforced CGC (SCGC). The governing laws of mass loss rate, relative dynamic elastic modulus and load-midspan deflection curve were obtained on the base of the analysis of testing results. The damage mechanisms of the SCGC under the FTCs were analyzed using the results of scanning electron microscopy (SEM). Based on the Lemaitre's strain equivalence principle and Krajcinovic's vector damage theory, a damage evolution model of the SCGC under the FTCs was established by introducing the damage variable of the SCGC satisfying Weibull distribution. The results show an increasing mass loss rate of the SCGC and a decreasing relative dynamic elastic modulus with an increasing mass replacement rate of coal gangue. The proper content of the steel fiber can reduce the mass loss rate of concrete by 10~40% and the relative loss rate of dynamic elastic modulus of concrete by 2~8%, thus significantly improving the ductility and toughness of the concrete. The established damage evolution model is well validated by the experimental results, which further help to improve the modelling accuracy. This study provides key experimental data and a theoretical basis for a wider range of proper utilization of coal gangue in cold regions.

A construct of adipose-derived mesenchymal stem cells-laden collagen scaffold for fertility restoration by inhibiting fibrosis in a rat model of endometrial injury.

Severe endometrium damage causes pathological conditions such as thin endometrium and intrauterine adhesion, resulting in uterine factor infertility. Mesenchymal stem cell (MSC) therapy is a promising strategy in endometrial repair; yet, exogenous MSCs still raise concerns for safety and ethical issues. Human adipose-derived mesenchymal stem cells (ADMSCs) residing in adipose tissue have high translational potentials due to their autologous origin. To harness the high translation potentials of ADMSC in clinical endometrium regeneration, here we constructed an ADMSCs composited porous scaffold (CS/ADMSC) and evaluated its effectiveness on endometrial regeneration in a rat endometrium-injury model. We found that CS/ADMSC intrauterine implantation (i) promoted endometrial thickness and gland number, (ii) enhanced tissue angiogenesis, (iii) reduced fibrosis and (iv) restored fertility. We ascertained the pro-proliferation, pro-angiogenesis, immunomodulating and anti-fibrotic effects of CS/ADMSC in vitro and revealed that the CS/ADMSC influenced extracellular matrix composition and organization by a transcriptomic analysis. Our results demonstrated the effectiveness of CS/ADMSC for endometrial regeneration and provided solid proof for our future clinical study.

The association between the number of oocytes retrieved and cumulative live birth rate in different female age strata.

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 < 0.001). Age and number of oocytes retrieved are two independent factors affecting the CLBR. The discrepancy of the minimum number of oocytes retrieved for patients with different ages to achieve ideal CLBR is instructive for clinical practice. The practice of controlling the stimulation dose is feasible for patients ≤ 35 years who can achieve over 60% CLBR once the number of oocytes obtained is more than 6. However, additional stimulation cycles and accumulation of embryos are necessary for elderly group especially those ≥ 38 years old who need more than 14 oocytes to obtain higher live birth rate.

Interface coupling effect in biomass-derived iron sulfide nanomaterials triggering efficient hydrogen peroxide activation.

Slow electron migration in iron sulfide nanoparticles (C-FeS NPs) synthesized by co-precipitation severely limits the activation performance of hydrogen peroxide (H2O2). Herein, a biofunctional FeS NPs (P-FeS NPs) derived from Pinus massoniana Lamb biomass, with interface coupling effect, was used for enhanced H2O2 activation and norfloxacin (NOR) degradation. It was discovered that P-FeS NPs exhibited superior catalytic activity (100%) compared to C-FeS NPs (53.1%). Fe atoms of FeS NPs and hydroxyl groups (-OH) of Pinus massoniana Lamb biomass were mutually coupled to produce Fe-OH interfacial sites, which significantly increased the generation of multi-reactive species by accelerating the transfer of electrons across interfaces. Additionally, radical quenching tests elucidated that singlet oxygen (1O2) (66.6%) played a leading role, while hydroxyl radicals (•OH) (14.5%) and superoxide radicals (•O2-) (18.9%) were secondary oxidants. Finally, P-FeS NPs showed a high tolerance to a wide range of pH conditions and could remove 96.4% NOR from wastewater. Overall, this work generates important insights into understanding how green sustainable interfacial catalysts can accelerate catalytic activity.

The origins of potentially superior properties and multifunctionalities of carbon-nano zero-valent iron in the carbonization pyrolysis process.

Although carbon-nano zero-valent iron (C@nZVI) composites with unique properties have been used for environmental remediation, the origins of their superior properties and multifunctionalities of C@nZVI still need to be verified. Here, iron precursor nanoparticles (PML-Fe NPs) synthesized by Pinus massoniana Lamb and carbonized C@nZVI were systemically compared to reveal the origins of the structure and performance of C@nZVI composites. Characterizations showed that structure-modulated C@nZVI has favorable properties of good crystallinity, graphite carbon-rich structure but also defects when compared to PML-Fe NPs. The resultant carbon layer fundamentally improved its dispersion and anti-oxidation properties. Further experiments demonstrated that the evolution of material crystallinity, graphitization and defects affected the reaction pathway of hexavalent chromium (Cr(VI)), oxytetracycline hydrochloride (OTC), and 17ß-estradiol (ßE2). The multifunctionalities covered adsorption, reduction and catalytic oxidation. This study explains the origins of multifunctional C@nZVI by understanding the structure-property correlation in the carbonization process.

Impact of coexisting components in acid mine drainage on Sb(â ¢) oxidation by biosynthesized iron nanoparticles.

Despite the oxidation mechanism of antimonite (Sb(Ⅲ)) by biosynthesized iron nanoparticles (Fe NPs) has been reported, the impact of coexisting components in acid mine drainage (AMD) on the Sb(III) oxidation by Fe NPs is unknown. Herein, how the coexisting components in AMD affect Sb(Ⅲ) oxidation by Fe NPs was investigated. Firstly, Fe NPs achieved complete oxidation of Sb(Ⅲ) (100%), while only 65.0% of Sb(Ⅲ) was oxidized when As(Ⅲ) was added, due to competitive oxidation between As(Ⅲ) and Sb(Ⅲ), which was verified by characterization analysis. Secondly, the decline in solution pH improved Sb(Ⅲ) oxidation from 69.5% (pH 4) to 100% (pH 2), which could be attributed to the rise of Fe3+ in solution promoting the electron transfer between Sb(Ⅲ) and Fe NPs. Thirdly, the oxidation efficiencies of Sb(Ⅲ) fell by 14.9 and 44.2% following the addition of oxalic and citric acid, respectively, resulting from the fact that these two acids reduced the redox potential of Fe NPs, thereby inhibiting Sb(Ⅲ) oxidation by Fe NPs. Finally, the interference effect of coexisting ions was studied, where PO43- significantly reduced Sb(Ⅲ) oxidation efficiency due to the occupation of the surface-active sites on Fe NPs. Overall, this study has significant implications for the prevention of Sb contamination in AMD.

Anchoring grassland sustainability with a nature-based small burrowing mammal control strategy.

Over the last 40 years, a burrowing mammal eradication policy has been prevalent on the Qinghai-Tibetan Plateau (QTP). This policy is based on similar burrowing mammal eradication programs in other areas and is justified on the assumptions that burrowing mammals compete with livestock for forage and contribute to grassland degradation. However, there is no clear theoretical or experimental evidence supporting these assumptions. This paper synthesizes the ecological functioning of small burrowing mammals in natural grasslands and discusses the irrationality and consequences of burrowing mammal eradication for sustainable livestock grazing and grassland degradation. Past burrowing mammal eradication efforts have failed because increased food availability for the remaining rodents and reduced predator populations led to rapid population rebounds. Herbivores differ in diet, and there is clear evidence that burrowing mammals, especially plateau zokors Myospalax baileyi, have a different diet than livestock. In QTP meadows, burrowing mammal eradication induces a shift towards plant communities with fewer species preferred by livestock and more species preferred by burrowing mammals. Thus, eradicating burrowing mammals has the opposite effect, a reduction in livestock preferred vegetation. We suggest that the policy of poisoning burrowing mammals needs to be reconsidered and revoked as soon as possible. We argue that incorporating density-dependent factors such as predation and food availability are essential for maintaining a low burrowing mammal density. For degraded grasslands, we suggest that the optimal sustainable approach is to decrease the intensity of livestock grazing. Lower grazing induces changes in vegetation structure and plant species composition that increases predation on burrowing mammals and decreases the abundance of plants preferred by burrowing mammals. Such a nature-based grassland management system maintains the density of burrowing mammals at a low stable density while minimizing human management and interventions.

Cytoplasmic YAP1-mediated ESCRT-III assembly promotes autophagic cell death and is ubiquitinated by NEDD4L in breast cancer.

BACKGROUND: Nuclear Yes1-associated transcriptional regulator (YAP1) promotes tumor progression. However, the function of cytoplasmic YAP1 in breast cancer cells and its impact on the survival of breast cancer patients remain unclear. Our research aimed to explore the biological function of cytoplasmic YAP1 in breast cancer cells and the possibility of cytoplasmic YAP1 as a predictive marker of breast cancer survival. METHODS: We constructed cell mutant models, including NLS-YAP15SA (nuclear localized), YAP1S94A (incapable of binding to the TEA domain transcription factor family) and YAP1S127D (cytoplasmic localized), and used Cell Counting Kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays, and Western blotting (WB) analysis to detect cell proliferation and apoptosis. The specific mechanism of cytoplasmic YAP1-mediated endosomal sorting complexes required for transport III (ESCRT-III) assembly was studied by co-immunoprecipitation, immunofluorescence staining, and WB analysis. Epigallocatechin gallate (EGCG) was used to simulate YAP1 retention in the cytoplasm in in vitro and in vivo experiments to study the function of cytoplasmic YAP1. YAP1 binding to NEDD4-like E3 ubiquitin protein ligase (NEDD4L) was identified using mass spectrometry and was verified in vitro. Breast tissue microarrays were used to analyze the relationship between cytoplasmic YAP1 expression and the survival of breast cancer patients. RESULTS: YAP1 was mainly expressed in the cytoplasm in breast cancer cells. Cytoplasmic YAP1 promoted autophagic death of breast cancer cells. Cytoplasmic YAP1 bound to the ESCRT-III complex subunits charged multivesicular body protein 2B (CHMP2B) and vacuolar protein sorting 4 homolog B (VPS4B), promoting assembly of CHMP2B-VPS4B and activating autophagosome formation. EGCG retained YAP1 in the cytoplasm, promoting the assembly of CHMP2B-VPS4B to promote autophagic death of breast cancer cells. YAP1 bound to NEDD4L, and NEDD4L mediated ubiquitination and degradation of YAP1. Breast tissue microarrays revealed that high levels of cytoplasmic YAP1 were beneficial to the survival of breast cancer patients. CONCLUSIONS: Cytoplasmic YAP1 mediated autophagic death of breast cancer cells by promoting assembly of the ESCRT-III complex; furthermore, we established a new breast cancer survival prediction model based on cytoplasmic YAP1 expression.

Misdiagnosis of placental mesenchymal dysplasia as pregnancy with hydatidiform mole: A case report and literature review.

RATIONALE: Placental mesenchymal dysplasia (PMD) is a rare placental disease frequently associated with severe maternal and/or fetal complications. Its sonographic appearance is very similar to that of a hydatidiform mole. Hence, PMD is easily misdiagnosed as a hydatidiform mole. In this study, we reported the clinical features of PMD and analyzed its relationship to other severe maternal and/or fetal complications. PATIENT CONCERNS: A 28-year-old female, gravida 2, para 1, was referred to our maternal and child health hospital at 15 weeks + 2 days due to an ultrasonic diagnosis of partial hydatidiform mole. Analysis of chromosome karyotype + mononucleotide-based gene microarray by amniocentesis at the 19th week of gestation showed that fetal amniocentesis chromosome 46, XN, high-resolution chromosome microarray analysis of Affymetrix CytoScan 750K Array revealed a 210 kb fragment deletion in chromosome 2p16.3 containing NRXN1, an OMIM gene, the deleted fragment was derived from a mother with a normal phenotype. The pregnant woman delivered a healthy baby girl at 36 weeks + 5 days. DIAGNOSES: Based on the clinical characteristics, imaging, and genetic test findings, the postoperative diagnosis was PMD. INTERVENTION: Because of "Scar uterus" and "Pregnancy with hydatidiform mole," a 2490 g female infant was delivered by cesarean section at 36 weeks + 5 days of gestation with an Apgar score of 9/9. OUTCOMES: The maternal human chorionic gonadotropin level decreased to the normal range after 10 days of delivery, and the infant was not found abnormal after 3 months of follow-up. LESSONS: From our cases and 19 other cases obtained from the PMD literature review are associated with unique clinical, laboratory, and imaging features compared with a hydatidiform mole, such as stained glass sign, normal serum levels of serum human chorionic gonadotropin, elevated alpha-fetoprotein levels and female fetus.

Association of Objective and Self-Reported Sleep Duration With All-Cause and Cardiovascular Disease Mortality: A Community-Based Study.

Background Previous studies found an association between self-reported sleep duration and mortality. This study aimed to compare the effects of objective and self-reported sleep duration on all-cause and cardiovascular disease (CVD) mortality. Methods and Results A total of 2341 men and 2686 women (aged 63.9±11.1 years) were selected from the SHHS (Sleep Heart Health Study). Objective sleep duration was acquired using in-home polysomnography records, and self-reported sleep duration on weekdays and weekends was based on a sleep habits questionnaire. The sleep duration was categorized as ≤4 hours, 4 to 5 hours, 5 to 6 hours, 6 to 7 hours, 7 to 8 hours, and >8 hours. Multivariable Cox regression analysis was used to investigate the association of objective and self-reported sleep duration with all-cause and CVD mortality. During a mean follow-up period of 11 years, 1172 (23.3%) participants died, including 359 (7.1%) deaths from CVD. All-cause and CVD mortality rates decreased gradually with increasing objective sleep duration. In multivariable Cox regression analysis, the greatest association for all-cause and CVD mortality was with an objective sleep duration of 5 hours or shorter. In addition, we found a J-shaped association of self-reported sleep duration on both weekdays and weekends with all-cause and CVD mortality. Self-reported short (≤4 hours) and long (>8 hours) sleep duration on weekdays and weekends were associated with an increased risk of all-cause and CVD mortality compared with 7 to 8 hours sleep duration. Furthermore, a weak correlation was observed between objective and self-reported sleep duration. Conclusions This study showed that both objective and self-reported sleep duration were associated with all-cause and CVD mortality, but with different characteristics. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00005275; Unique identifier: NCT00005275.

Decreased Expression of EZH2 in Granulosa Cells Contributes to Endometriosis-Associated Infertility by Targeting IL-1R2.

The mechanism by which endometriosis, a common gynecological disease characterized by chronic pelvic pain and infertility, causes infertility remains elusive. Luteinized unruptured follicle syndrome, the most common type of ovulatory dysfunction, is a cause of endometriosis-associated infertility involving reduced numbers of retrieved and mature oocytes. Ovulation is controlled by luteinizing hormone and paracrine signals produced within the follicle microenvironment. Generally, interleukin (IL)-1ß is elevated in endometriosis follicular fluid, whereby it amplifies ovulation signals by activating extracellular-regulated kinase 1/2 and CCAAT/enhancer binding protein ß pathways. However, this amplification of ovulation by IL-1ß does not occur in patients with endometriosis. To illuminate the mechanism of ovulatory dysfunction in endometriosis, we analyzed the effect of oxidative stress and IL-1ß expression on endometriosis follicles. We found that oxidative stress decreased EZH2 expression and reduced H3K27Me3 levels in endometriosis ovarian granulosa cells (GCs). Selective Ezh2 depletion in mice ovarian GCs reduced fertility by disturbing cumulus-oocyte complex expansion and reducing epidermal growth factor-like factor expression. Gene expression and H3K27Me3 ChIP-sequencing (ChIP-Seq) of GCs revealed IL-1 receptor 2 (IL-1R2), a high-affinity IL-1ß-receptor that suppresses IL-1ß-mediated inflammatory cascades during ovulation, as a crucial target gene of the EZH2-H3K27Me3 axis. Moreover, IL-1ß addition did not restore ovulation upon Ezh2 knockdown, indicating a vital function of IL-1R2 in endometriosis. Thus, our findings show that reducing EZH2 and H3K27Me3 in GCs suppressed ovulatory signals by increasing IL-1R2 expression, which may ultimately contribute to endometriosis-associated infertility.

A novel solution for freezing individual spermatozoa using a right angular cryopiece embedded in a grooved petri dish.

Herein, we introduced a novel individual sperm freezing device named SpermCD, which consists of a right angular cryopiece (RA-Cryopiece, or "C") and a grooved petri dish ("D"). SpermCD allows embryologists to transfer sperm and perform ICSI on the same focal plane. Thirty-five patients underwent single sperm cryopreservation using SpermCD, including four patients with non-obstructive azoospermia (NOA), 14 patients with virtual azoospermia and 17 patients with cryptozoospermia. One hundred and twenty-five cryopreserved spermatozoa from nine patients were thawed on the day of the oocyte retrieval and 121 spermatozoa were found, with a sperm recovery rate of 97.1 ± 4.6%. Sixty-five MII oocytes from their spouse were injected with thawed sperm. Normal fertilization and high-quality embryo rates were 68.0% ± 33.2% and 24.4% ± 22.2%. Nineteen transplantable embryos were formed after fertilization with frozen sperm, eight of which were transplanted in five couples, resulting in four successful deliveries. SpermCD is a simple and practical individual sperm freezing device.

S100P promotes trophoblast syncytialization during early placenta development by regulating YAP1.

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 ß-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.

An Acellular Scaffold Facilitates Endometrial Regeneration and Fertility Restoration via Recruiting Endogenous Mesenchymal Stem Cells.

Severe intrauterine adhesions (IUAs), characterized by inadequate endometrial repair and fibrosis, can lead to infertility. Stem cell-based therapies, which deliver mesenchymal stem cells (MSCs) to the wound site, hold a considerable promise for endometrium regeneration. However, some notable hurdles, such as stemness loss, immunogenicity, low retention and survival rate, limit their clinical application. Evidence shows a strategy of mobilizing endogenous MSCs recruitment can overcome the traditional limitations of exogenous stem cell-based therapies. Here, an acellular biomaterial named stromal derived factor-1 alpha (SDF-1α)/E7-modified collagen scaffold (CES) is explored. CES based on harnessing the innate regenerative potential of the body enables near-complete endometrium regeneration and fertility restoration both in a rat endometrium acute damage model and a rat IUA model. Mechanistically, the CES implantation promotes endogenous MSCs recruitment via a macrophage-coordinated strategy; then the homing MSCs exert the function of immunomodulation and altered local microenvironments toward regeneration. To conclude, CES, which can harness endogenous MSCs and overcome the traditional limitations of cell-based therapies, can serve as a clinically feasible and cell-free strategy with high therapeutic efficiency for IUA treatment.

Trophoblast-Derived Extracellular Vesicles Promote Preeclampsia by Regulating Macrophage Polarization.

BACKGROUND: Systemic inflammation caused by dysfunctional macrophages is a crucial pathogenetic event in preeclampsia (PE). Trophoblast-derived extracellular vesicles (T-EVs) are potent immune cell signaling modulators in pregnancy. Herein, we aimed to investigate T-EVs' effect and mechanism on macrophage polarization and its role in PE pathogenesis, which remain unclear. METHODS: Flow cytometry and immunochemistry were used to determine placental macrophage phenotypes. T-EVs were immuno-isolated via placental alkaline phosphatase antibody and identified by transmission electron microscopy and nanoparticle tracking analysis. Quantitative real-time polymerase chain reaction and flow cytometry were used to examine the effects of T-EVs on macrophage polarization, and correlation analysis of T-EVs lipidomics and macrophages transcriptome were performed to explore how T-EVs modulate macrophages. Animal experiments were established to investigate the relationship among PE, T-EVs, and macrophages. RESULTS: Macrophages shift from the M2 to M1 phenotype in the preeclamptic placenta. Also, T-EVs from women with PE (PE-EVs) significantly upregulated M1 gene markers and significantly downregulated CD163 expression in macrophages compared with T-EVs in women with normal pregnancies (NP-EVs). Mechanistically, correlation analysis with T-EVs lipidome and the transcriptome of macrophages treated with PE-EVs or NP-EVs indicated that 37 lipids altered in PE-EVs considerably affected classical inflammatory biological pathways in macrophages. Finally, animal experiments revealed that PE-EVs triggered PE-like symptoms in pregnant mice, which were alleviated after macrophage depletion. CONCLUSIONS: T-EVs from women with PE could promote preeclampsia by inducing macrophage imbalance polarization, signifying a potential novel interventional target for the prevention and management of PE.

Factors affecting clinical outcomes after IVF-ET for infertile young patients with ovarian endometrioma: A 5-year retrospective cohort study.

This study aimed to compare ovarian reserve function and outcomes after in vitro fertilization and embryo transfer (IVF-ET) for young women with pelvic endometriosis with or without ovarian endometrioma. We explored the main factors influencing pregnancy outcomes in young patients with endometrioma. A total of 619 patients ≤38 years of age who underwent IVF-ET in our reproductive center between January 2011 and December 2015 were recruited. Among these patients, 398 had pelvic endometriosis with ovarian endometrioma and 221 had pelvic endometriosis without ovarian endometrioma. Patients underwent ovulation induction during IVF-ET. The general conditions and clinical outcomes of IVF-ET treatment were compared. Key factors affecting the success of IVF-ET treatment for endometriomas were analyzed. During IVF-ET treatment, the numbers of retrieved oocytes and 2-pronuclei (2PN) embryos in all age groups (P < .01), and the number of 2PN high-quality embryos in patients under 30 years of age was lower in the pelvic endometriosis with ovarian endometrioma group than in the pelvic endometriosis alone group (P < .05). Logistic regression analysis showed the number of antral follicles, basal follicle-stimulating hormone (bFSH) levels, number of oocytes, number of 2PN embryos, and number of 2PN high-quality embryos were significantly related to the successful outcome of IVF-ET. Among these, the number of 2PN high-quality embryos was the only independent predictive factor. Ovarian endometrioma significantly impairs ovarian reserve function and ultimately affects the therapeutic efficacy of IVF-ET. Obtaining more 2PN high-quality embryos was important for IVF-ET treatment of young patients with ovarian endometriomas.

Mechanism for the simultaneous removal of Sb(III) and Sb(V) from mining wastewater by phytosynthesized iron nanoparticles.

Since antimony (Sb) is a toxic metalloid cost-effective method for the simultaneous removal of the two major Sb species from mining wastewater has attracted much attention. In this study, phytosynthesized iron nanoparticles (nFe) prepared using a eucalyptus leaf extract were successfully used to simultaneously remove Sb(III) and Sb(V) via an adsorption and oxidation mechanism with removal efficiencies of 100 and 97.7% for Sb(III) and Sb(V), respectively. Advanced analysis using X-ray photoelectron spectroscopy (XPS), ion chromatography-atomic fluorescence spectroscopy (IC-AFS), and electrochemical analysis confirmed that Sb(III) was oxidized to Sb(V) by Fe(III) on the nFe surface while Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS) indicated that both Sb(III) and Sb(V) were adsorbed onto nFe. Adsorption of both Sb(III) and Sb(V) best fit the Langmuir adsorption model with R2 of 0.999 and 0.989, respectively and both followed pseudo-second-order kinetics with R2 of 0.999 and 0.981, respectively. Furthermore, the adsorption rate of Sb(III) was faster than that of Sb(V) due to inner-sphere complex formation, and the Fe-O bonds in the asymmetric tetrahedron structure of Sb(III) were easier to break due to a lower energy barrier (0.863 eV). Consequently, a simultaneous removal mechanism of Sb(III) and Sb(V) was proposed. Finally, nFe was used practically to remove Sb in mining wastewater with a removal efficiency of 93.5%, demonstrating that nFe have significant potential to remove Sb in contaminated mining wastewaters.