Melatonin alleviates myocardial dysfunction through inhibition of endothelial-to-mesenchymal transition via the NF-κB pathway.

Endothelial-to-mesenchymal transition (EndMT) is a complex biological process of cellular transdifferentiation by which endothelial cells (ECs) lose their characteristics and acquire mesenchymal properties, leading to cardiovascular remodeling and complications in the adult cardiovascular diseases environment. Melatonin is involved in numerous physiological and pathological processes, including aging, and has anti-inflammatory and antioxidant activities. This molecule is an effective therapeutic candidate for preventing oxidative stress, regulating endothelial function, and maintaining the EndMT balance to provide cardiovascular protection. Although recent studies have documented improved cardiac function by melatonin, the mechanism of action of melatonin on EndMT remains unclear. The present study investigated the effects of melatonin on induced EndMT by transforming growth factor-ß2/interleukin-1ß in both in vivo and in vitro models. The results revealed that melatonin reduced the migratory ability and reactive oxygen species levels of the cells and ameliorated mitochondrial dysfunction in vitro. Our findings indicate that melatonin prevents endothelial dysfunction and inhibits EndMT by activating related pathways, including nuclear factor kappa B and Smad. We also demonstrated that this molecule plays a crucial role in restoring cardiac function by regulating the EndMT process in the ischemic myocardial condition, both in vessel organoids and myocardial infarction (MI) animal models. In conclusion, melatonin is a promising agent that attenuates EC dysfunction and ameliorates cardiac damage compromising the EndMT process after MI.

Complete and Incomplete Alcohol Sclerotherapy for Treatment of Symptomatic Hepatic Cysts: Comparison of Volume Reduction and Clinical Outcomes.

Background: The purpose of this study was to compare the efficacy of incomplete alcohol sclerotherapy with complete treatment for hepatic cysts. Methods: From 2005 to 2021, a total of 80 patients (19 males, 61 females; median age 65 years; age range, 42-86 years) who underwent alcohol sclerotherapy for symptomatic benign hepatic cysts were enrolled and retrospectively reviewed. Complete treatment was defined as injecting 25-33% of the aspirated cyst volume with alcohol in 2-3 cycles, with a maximum of 100 mL per cycle. The overall volume reduction rate was compared between the complete and incomplete treatment groups. The response, based on cystic volume reduction, was classified as a complete regression (CR), near-complete regression (NCR), partial regression (PR), or no response (NR). CR and NCR were considered objective responses. Among 80 patients with 85 hepatic cysts, 26 patients with 29 hepatic cysts received incomplete treatment. Results: The overall volume reduction rate was not significantly different between the complete and incomplete treatment groups (94.39% vs. 95.47%, respectively, p = 0.623). The CR and NCR groups showed a significantly higher rate of symptom improvement than the PR and NR groups (p = 0.043). Conclusions: In conclusion, the efficacy of incomplete alcohol sclerotherapy was not inferior to that of complete treatment.

Insights into structural defect formation in individual InP/ZnSe/ZnS quantum dots under UV oxidation.

InP/ZnSe/ZnS quantum dots (QDs) stand as promising candidates for advancing QD-organic light-emitting diodes (QLED), but low emission efficiency due to their susceptibility to oxidation impedes applications. Structural defects play important roles in the emission efficiency degradation of QDs, but the formation mechanism of defects in oxidized QDs has been less investigated. Here, we investigated the impact of diverse structural defects formation on individual QDs and propagation during UV-facilitated oxidation using high-resolution (scanning) transmission electron microscopy. UV-facilitated oxidation of the QDs alters shell morphology by the formation of surface oxides, leaving ZnSe surfaces poorly passivated. Further oxidation leads to the formation of structural defects, such as dislocations, and induces strain at the oxide-QD interfaces, facilitating In diffusion from the QD core. These changes in the QD structures result in emission quenching. This study provides insight into the formation of structural defects through photo-oxidation, and their effects on emission properties of QDs.

Considerations on the methane correction factor and fraction of methane parameters in the IPCC first-order decay model for active aeration landfills.

Understanding the behavior of organic carbon in municipal solid waste landfills is a major challenge for estimating methane (CH4) emissions using the Intergovernmental Panel on Climate Change (IPCC) first-order decay (FOD) model. According to the IPCC guidelines, the default values of CH4 correction factor (MCF) and fraction of CH4 (F) for active aeration landfills are set as 0.4 and 0.5, respectively. However, whether it is reasonable to apply the default values of MCF and F to active aeration landfills is questionable. This study aims to estimate the MCF and develop a method to determine the F value for active aeration landfills. In this investigation, three landfill sites were operated as active aeration landfills to estimate the MCF and the F. The study results indicate that MCF values were lower than the default value of 0.4 provided in the IPCC guidelines under aerobic conditions with a CH4 concentration of less than 5%. According to the carbon balance analyses, there was a mismatch between the theoretical CH4/CO2 ratio based on the F default value of 0.5 and the measured CH4/CO2 ratio. Using the F calculation method proposed in this study, the theoretical CH4/CO2 ratio and the measured CH4/CO2 ratio was calculated equally. The F values during air injection ranged from 0.25 to 0.93 at three landfill sites, suggesting that adapting the F default value of 0.5 for active aeration landfills may lead to significant errors in the estimation of CH4 emissions using the IPCC FOD model.

Epigallocatechin-3-Gallate Attenuates Myocardial Dysfunction via Inhibition of Endothelial-to-Mesenchymal Transition.

Cardiac tissue damage following ischemia leads to cardiomyocyte apoptosis and myocardial fibrosis. Epigallocatechin-3-gallate (EGCG), an active polyphenol flavonoid or catechin, exerts bioactivity in tissues with various diseases and protects ischemic myocardium; however, its association with the endothelial-to-mesenchymal transition (EndMT) is unknown. Human umbilical vein endothelial cells (HUVECs) pretreated with transforming growth factor ß2 (TGF-ß2) and interleukin 1ß (IL-1ß) were treated with EGCG to verify cellular function. In addition, EGCG is involved in RhoA GTPase transmission, resulting in reduced cell mobility, oxidative stress, and inflammation-related factors. A mouse myocardial infarction (MI) model was used to confirm the association between EGCG and EndMT in vivo. In the EGCG-treated group, ischemic tissue was regenerated by regulating proteins involved in the EndMT process, and cardioprotection was induced by positively regulating apoptosis and fibrosis of cardiomyocytes. Furthermore, EGCG can reactivate myocardial function due to EndMT inhibition. In summary, our findings confirm that EGCG is an impact activator controlling the cardiac EndMT process derived from ischemic conditions and suggest that supplementation with EGCG may be beneficial in the prevention of cardiovascular disease.

Visible-Light Photoredox-Catalyzed Giese Reaction of α-Silyl Ethers with Various Michael Acceptors.

We developed a photocatalyzed Giese reaction of various weakly activated Michael acceptors with a neutral silicon-based radical precursor and applied it at large-scale using a continuous flow reactor. The developed method successfully overcomes the substrate scope limitations of previous studies, shows good functional groups tolerance, and affords good to excellent yields. On the basis of mechanistic studies, we propose a reaction mechanism that involves an in situ generated alkoxymethyl radical via single-electron oxidation of α-trimethylsilyl-substituted ethers.

Regulation of Inflammation-Mediated Endothelial to Mesenchymal Transition with Echinochrome a for Improving Myocardial Dysfunction.

Endothelial-mesenchymal transition (EndMT) is a process by which endothelial cells (ECs) transition into mesenchymal cells (e.g., myofibroblasts and smooth muscle cells) and induce fibrosis of cells/tissues, due to ischemic conditions in the heart. Previously, we reported that echinochrome A (EchA) derived from sea urchin shells can modulate cardiovascular disease by promoting anti-inflammatory and antioxidant activity; however, the mechanism underlying these effects was unclear. We investigated the role of EchA in the EndMT process by treating human umbilical vein ECs (HUVECs) with TGF-ß2 and IL-1ß, and confirmed the regulation of cell migration, inflammatory, oxidative responses and mitochondrial dysfunction. Moreover, we developed an EndMT-induced myocardial infarction (MI) model to investigate the effect of EchA in vivo. After EchA was administered once a day for a total of 3 days, the histological and functional improvement of the myocardium was investigated to confirm the control of the EndMT. We concluded that EchA negatively regulates early or inflammation-related EndMT and reduces the myofibroblast proportion and fibrosis area, meaning that it may be a potential therapy for cardiac regeneration or cardioprotection from scar formation and cardiac fibrosis due to tissue granulation. Our findings encourage the study of marine bioactive compounds for the discovery of new therapeutics for recovering ischemic cardiac injuries.

Highly efficient blue InGaN nanoscale light-emitting diodes.

Indium gallium nitride (InGaN)-based micro-LEDs (µLEDs) are suitable for meeting ever-increasing demands for high-performance displays owing to their high efficiency, brightness and stability1-5. However, µLEDs have a large problem in that the external quantum efficiency (EQE) decreases with the size reduction6-9. Here we demonstrate a blue InGaN/GaN multiple quantum well (MQW) nanorod-LED (nLED) with high EQE. To overcome the size-dependent EQE reduction problem8,9, we studied the interaction between the GaN surface and the sidewall passivation layer through various analyses. Minimizing the point defects created during the passivation process is crucial to manufacturing high-performance nLEDs. Notably, the sol-gel method is advantageous for the passivation because SiO2 nanoparticles are adsorbed on the GaN surface, thereby minimizing its atomic interactions. The fabricated nLEDs showed an EQE of 20.2 ± 0.6%, the highest EQE value ever reported for the LED in the nanoscale. This work opens the way for manufacturing self-emissive nLED displays that can become an enabling technology for next-generation displays.

Weak base-promoted selective rearrangement of oxaziridines to amides via visible-light photoredox catalysis.

The selective rearrangement of oxaziridines to amides via a single electron transfer (SET) pathway is unexplored. In this study, we present a weak base-promoted selective rearrangement of oxaziridines to amides via visible-light photoredox catalysis. The developed method shows excellent functional group tolerance with a broad substrate scope and good to excellent yields. Furthermore, control experiments and density functional theory (DFT) calculations are performed to gain insight into the reactivity and selectivity.

The Effect of Additional Embryo Transfer on the Pregnancy Rate in Young Women Receiving in vitro Fertilization: A Natural Experiment Study.

PURPOSE: To assess the impact of additional embryo transfer (ET) on pregnancy in young women, we used a natural-experiment approach. PATIENTS AND METHODS: The design was based on the national policy of South Korea limiting the number of embryos transferred in vitro fertilization (IVF):≦2 embryos on day 2-4 or one on day 5-6 for patients aged <35, with one extra embryo allowed for patients aged ≥35. Using the data from 1909 ET cycles of 1287 women aged ≥34 and ≤35, we calculated adjusted risk ratios (RRs) for pregnancy. RESULTS: Half of cycles were undertaken by women aged 35, and additional ET was performed in 68.7% of them. Intrauterine pregnancy (45.2% vs 51.3%) and multiple gestation (30.5% vs 6.9%) were more common in women aged 35 than in those aged 34. The RR for intrauterine pregnancy was 1.34 (95% confidence interval: 1.12-1.59) when comparing double ET to single ET in frozen day 5-6 cycles. CONCLUSION: We observed no evidence of a higher probability of pregnancy with additional ET in fresh or frozen day 3-4 ET, or in fresh day 5-6 ET of women aged 35. Additional ET may not increase the successful pregnancy rate in the 35-year-old group, unless it is a frozen day 5-6 ET cycle.

Multiplexed targeting of miRNA-210 in stem cell-derived extracellular vesicles promotes selective regeneration in ischemic hearts.

Extracellular vesicles (EVs) are cell derivatives containing diverse cellular molecules, have various physiological properties and are also present in stem cells used for regenerative therapy. We selected a "multiplexed target" that demonstrates multiple effects on various cardiovascular cells, while functioning as a cargo of EVs. We screened various microRNAs (miRs) and identified miR-210 as a candidate target for survival and angiogenic function. We confirmed the cellular and biological functions of EV-210 (EVs derived from ASCmiR-210) secreted from adipose-derived stem cells (ASCs) transfected with miR-210 (ASCmiR-210). Under hypoxic conditions, we observed that ASCmiR-210 inhibits apoptosis by modulating protein tyrosine phosphatase 1B (PTP1B) and death-associated protein kinase 1 (DAPK1). In hypoxic endothelial cells, EV-210 exerted its angiogenic capacity by inhibiting Ephrin A (EFNA3). Furthermore, EV-210 enhanced cell survival under the control of PTP1B and induced antiapoptotic effects in hypoxic H9c2 cells. In cardiac fibroblasts, the fibrotic ratio was reduced after exposure to EV-210, but EVs derived from ASCmiR-210 did not communicate with fibroblasts. Finally, we observed the functional restoration of the ischemia/reperfusion-injured heart by maintaining the intercommunication of EVs and cardiovascular cells derived from ASCmiR-210. These results suggest that the multiplexed target with ASCmiR-210 is a useful tool for cardiovascular regeneration.

The Efficacy of Cone-Beam CT-Based Perfusion Mapping in Evaluation of Tissue Perfusion in Peripheral Arterial Disease.

This study investigated the use of cone-beam computed tomography (CBCT)-based perfusion mapping during percutaneous transluminal angioplasty (PTA) to predict clinical outcome in the peripheral arterial disease (PAD). From January 2016 to March 2020, 43 patients (28 male, 15 female; mean age, 69) with 51 limbs, who underwent PTA with CBCT-based foot perfusion mapping for PAD were included. Parenchymal blood volume (PBV) of foot was measured. Clinical response was investigated based on medical records. Predictive value for clinical success was evaluated using multiple logistic regression with C-statistics. Two reviewers visually assessed the improvement on angiography and CBCT-based foot perfusion mapping; inter-observer agreement of clinical success between the two were measured. Technical and clinical success rate of PTA was 90.8% and 68.6%, respectively. In multiple logistic regression, the maximum value of PBV (PBVmax) on perfusion mapping after PTA was significant (p = 0.03) for evaluating clinical success with the highest C-statistic (0.84). Using a cutoff of 235.7 mL/L for PBVmax after PTA, area under curve for prediction of clinical success was 0.664, and sensitivity and specificity were 71.4% and 68.8%, respectively. Consistency in prediction of clinical success between the two reviewers was almost perfect for CBCT-based foot perfusion mapping.

Endovascular Treatment for Lower Extremity Deep Vein Thrombosis: An Overview.

Lower extremity deep vein thrombosis (DVT) is a serious medical condition that can result in local pain and gait disturbance. DVT progression can also lead to death or major disability as a result of pulmonary embolism, postthrombotic syndrome, or limb amputation. However, early thrombus removal can rapidly relieve symptoms and prevent disease progression. Various endovascular procedures have been developed in the recent years to treat DVT, and endovascular treatment has been established as one of the major therapeutic methods to treat lower extremity DVT. However, the treatment of lower extremity DVT varies according to the disease duration, location of affected vessels, and the presence of symptoms. This article reviews and discusses effective endovascular treatment methods for lower extremity DVT.

Percutaneous radiologic gastrostomy with single gastropexy: outcomes in 636 patients.

OBJECTIVES: This study aimed to assess the technical success and overall complication rate of percutaneous radiologic gastrostomy (PRG) with single gastropexy using a separate tract from that used for tube placement. METHODS: From January 2014 to December 2018, 636 patients (469 men, 167 women; mean age 66.8 years; age range, 22-98 years) underwent PRG using single gastropexy at a tertiary center. Preprocedural computed tomography (CT) was recommended if there were no data on the location of the stomach on previous CT. After a single anchor was applied, the PRG tube was inserted through a separate tract from that used for tube placement. The technical success rate and major and minor complications were retrospectively reviewed. The number of patients and percentages were used as descriptive statistics for evaluating the complication rate. RESULTS: The technical success rate of PRG with single gastropexy was 99.2% (631/636). There were 32 complications among the 631 procedures. There were 19 (3.0%) major complications, including peritonitis (n = 7), migration (n = 5), infection (n=4), malposition (n = 2), and bleeding (n = 1). There were 13 (2.1%) minor complications, including local infection (n = 11), malfunction (n = 1), and pneumoperitoneum (n = 1). The overall complication rate within 30 days of PRG placement was 4.1% (26/631). CONCLUSIONS: PRG with single gastropexy using a separate tract from that used for tube placement is technically feasible with a low complication rate. KEY POINTS: • Percutaneous radiologic gastrostomy with single gastropexy using a separate tract from that used for tube placement is technically feasible. • Complications including peritonitis and bleeding were comparatively low with the conventional technique.

How to Treat Peripheral Arteriovenous Malformations.

Arteriovenous malformations (AVMs) are direct communications between primitive reticular networks of dysplastic vessels that have failed to mature into capillary vessels. Based on angiographic findings, peripheral AVMs can be classified into six types: type I, type IIa, type IIb, type IIc, type IIIa, and type IIIb. Treatment strategies vary with the types. Type I is treated by embolizing the fistula between the artery and the vein with coils. Type II (IIa, IIb, and IIc) AVM is treated as follows: first, reduce the blood flow velocity in the venous segment of the AVM with coils; second, perform ethanol embolotherapy of the residual shunts. Type IIIa is treated by transarterial catheterization of the feeding arteries and injection of diluted ethanol. Type IIIb is treated by transarterial or direct puncture approaches. A high concentration of ethanol is injected through the transarterial catheter or direct puncture needle. When the fistula is large, coil insertion is required to reduce the amount of ethanol. Type I and type II AVMs showed the best clinical results; type IIIb showed a satisfactory response rate. However, type IIIa showed the poorest response rate, either alone or in combination with other types. Clinical success can be achieved by using different treatment strategies for different angiographic AVM types.

Therapeutic outcomes of embolotherapy of extremity bone intraosseous arteriovenous malformation with ethanol, coils, and n-butyl cyanoacrylate.

OBJECTIVE: We evaluated the therapeutic outcomes of embolotherapy for bone arteriovenous malformations (AVMs) affecting the extremities using ethanol, coils, and n-butyl cyanoacrylate (NBCA). METHODS: We reviewed the data from 36 patients (18 males, 18 females; mean age 25 years; age range, 1-64 years) with bone AVMs affecting their extremities who had undergone embolotherapy using ethanol, coils, and NBCA from December 1996 to July 2019. Of the 36 patients, 19 had had pure bone AVMs and 17 mixed bone and soft tissue (MBS) AVMs. Embolotherapy was performed using direct puncture or a transvenous or an intra-arterial approach (range, 1-18 procedures; mean, 5 procedures). During the 178 embolotherapy procedures, ethanol was used in all 36 patients, except for 1. Coils were used in 14 patients, and NBCA and a lipiodol mixture in 9 patients. The therapeutic outcomes were evaluated by the clinical symptom response and the degree of devascularization on follow-up angiography or computed tomography. The major and minor complications were also evaluated. RESULTS: The clinical success (cure or markedly improvement) rate of embolotherapy for pure bone AVMs was significantly better than that for the MBS AVMs (88% vs 18%; P < .001). The complete devascularization rate of the bone AVM component of the MBS AVMs was 71%; however, the cure rate of the MBS AVMs was 0% owing to the remaining soft tissue AVMs. Of the 36 patients, 12 experienced complications, including 11 minor (2 skin bullae formation and 10 transient peripheral nerve injury) and 1 major (longstanding nerve palsy). CONCLUSIONS: Embolotherapy for bone AVMs affecting the extremities using ethanol, coils, and an NBCA mixture is effective and safe for the resolution or improvement of symptoms, especially in those with pure bone AVMs.

Correlations Between Stress, Depression, Body Mass Index, and Food Addiction Among Korean Nursing Students.

This study examined the relationships between stress, depression, body mass index, and food addiction in South Korean nursing students. Data from 323 nursing students in Seoul, Gangwon-do, Jeollanam-do, Gyeongsangnam-do, and Jeju-do were collected via self-report questionnaires and analyzed using chi-square tests, Mann-Whitney U tests, logistic regression analyses, and the receiver operating characteristic curve using SPSS 21.0. Overall, 7.1% of students were classified as having a food addiction. Stress and depression affected food addiction, and food addiction influenced obesity. Depression and stress combined were predictors of food addiction. These findings suggest that effective stress management and interventions for depression prevention may be beneficial to prevent food addiction in nursing students.

Regulation of alternative macrophage activation by MSCs derived hypoxic conditioned medium, via the TGF-ß1/Smad3 pathway.

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-ß1 expression, and TGF-ß1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-ß1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization. [BMB Reports 2020; 53(11): 600-604].

Clinical experience with distal transradial access for endovascular treatment of various noncoronary interventions in a multicenter study.

BACKGROUND: Transradial access is a well-known alternative to conventional transfemoral access for interventional procedures. Recently, transradial access through the "snuffbox", which lies in the radial dorsal aspect of the hand, has been introduced as a new technique with positional versatility. In this study, we aimed to evaluate the clinical feasibility and safety of distal transradial access for interventional procedures in a retrospective, multicenter study. MATERIAL & METHODS: Distal transradial access was attempted in 46 patients (36 men and 10 women; mean age, 64 years) who underwent 47 consecutive procedures from January 2018 to December 2019. Procedures included chemoembolization (19/47, 40.4%), bronchial artery embolization (7/47, 14.9%), renal intervention (3/47, 6.4%), arteriovenous fistula angioplasty (7/47, 14.9%), subclavian artery stenting (5/47, 10.6%), other embolization (5/47, 10.6%), and uterine artery embolization (1/47, 2.1%). We recorded the success rate of the procedures, complications, and postprocedural hemostasis time during the follow-up period. RESULTS: The technical success of distal transradial access without major complications was 97.9% (46/47). Of the 46 patients, one patient (2.2%) had a minor complication, which was a thrombotic segmental occlusion of the distal radial artery. Of the enrolled patients, only one patient did not complete the transradial access procedure via the snuffbox because the left proximal subclavian artery was occluded and a crossover to conventional transfemoral access was performed. The mean postprocedural hemostasis time was 131.7 minutes (range, 120-360 minutes). CONCLUSION: Distal transradial access can be a valid option for the endovascular treatment of various noncoronary interventions with technical feasibility and safety.

Peroxisome Proliferator-Activated Receptor Gamma Modulator Promotes Neonatal Mouse Primordial Follicle Activation In Vitro.

Peroxisome proliferator-activated receptor gamma (PPARγ) is known as a regulator of cellular functions, including adipogenesis and immune cell activation. The objectives of this study were to investigate the expression of PPARγ and identify the mechanism of primordial follicle activation via PPARγ modulators in mouse ovaries. We first measured the gene expression of PPARγ and determined its relationship with phosphatase and tensin homolog (PTEN), protein kinase B (AKT1), and forkhead box O3a (FOXO3a) expression in neonatal mouse ovaries. We then incubated neonatal mouse ovaries with PPARγ modulators, including rosiglitazone (a synthetic agonist of PPARγ), GW9662 (a synthetic antagonist of PPARγ), and cyclic phosphatidic acid (cPA, a physiological inhibitor of PPARγ), followed by transplantation into adult ovariectomized mice. After the maturation of the transplanted ovaries, primordial follicle growth activation, follicle growth, and embryonic development were evaluated. Finally, the delivery of live pups after embryo transfer into recipient mice was assessed. While PPARγ was expressed in ovaries from mice of all ages, its levels were significantly increased in ovaries from 20-day-old mice. In GW9662-treated ovaries in vitro, PTEN levels were decreased, AKT was activated, and FOXO3a was excluded from the nuclei of primordial follicles. After 1 month, cPA-pretreated, transplanted ovaries produced the highest numbers of oocytes and polar bodies, exhibited the most advanced embryonic development, and had the greatest blastocyst formation rate compared to the rosiglitazone- and GW9662-pretreated groups. Additionally, the successful delivery of live pups after embryo transfer into the recipient mice transplanted with cPA-pretreated ovaries was confirmed. Our study demonstrates that PPARγ participates in primordial follicle activation and development, possibly mediated in part by the PI3K/AKT signaling pathway. Although more studies are required, adapting these findings for the activation of human primordial follicles may lead to treatments for infertility that originates from poor ovarian reserves.