DDX04+ Stem Cells in the Ovaries of Postmenopausal Women: Existence and Differentiation Potential.

Ovarian aging is a pacemaker with multiple organ dysfunction. Recently, stem cells with the ability to generate new oocytes have been identified, which provides the possibility of stem cell therapy for ovarian aging. Several studies have revealed the existence of stem cells in the human postmenopausal ovary. In this study, we describe a new method using magnetic-activated cell sorting combined with differential adhesion to isolate DDX4+ stem cells from ovaries of postmenopausal women and show that the cells exhibit similar gene expression profiles and growth characteristics with primitive germ cells. Furthermore, the DDX4+ stem cells could enter the meiosis stage and differentiation into oocytes. The RNA-seq data of the differentiated oocytes shows that mitochondrial metabolism may play an important role in the oogenesis process of the DDX4+ stem cells. Through using the human ovarian cortical fragments transplantation model, we indicated that the GFP-DDX4+ stem cells differentiated into some GFP positive oocyte-like structure in vivo. Our study provided a new method for the isolation of DDX4+ stem cells from the ovaries of postmenopausal women and confirmed the ability of these stem cells to differentiate into oocytes.

Exploring a Better Adjuvant Treatment for Surgically Treated High-Grade Neuroendocrine Carcinoma of the Cervix.

OBJECTIVES: The objective of this study was to explore a better adjuvant treatment for patients with high-grade (HG) neuroendocrine cervical carcinomas (NECC) who had undergone surgery as a primary treatment. DESIGN: A retrospective cohort study, which involved women diagnosed as HG-NECC, was conducted in the Obstetrics and Gynecology Hospital of Fudan University. All patients had undergone radical surgery and pelvic lymphadenectomy with a laparotomy or a minimally invasive surgery. An analysis was made of the prognosis of HG-NECC. METHODS: Overall survival (OS) and progression-free survival (PFS) curves were drawn using the Kaplan-Meier method to be compared via log-rank tests. A Cox proportional hazards model was used to estimate the independent prognostic factors. RESULTS: A number of 110 patients diagnosed as HG-NECC at the pathological stage IA2 to IIIC2 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system were initially treated with a primary surgery between 2008 and 2020. The eligible patients had the median age of 42.5 years (range: 22-76), with the median follow-up period of 39.6 months (range: 1.0-156.6). The 5-year OS of the patients at pathological stage I, II, and III accounted for 84.9%, 85.7%, and 60.9%, respectively. The Kaplan-Meier survival curves revealed no significant differences in OS and PFS between postoperative chemoradiotherapy and chemotherapy alone (OS: p = 0.77; PFS: p = 0.41). Etoposide plus platinum therapy did not improve OS when compared with platinum plus paclitaxel therapy after surgery (p = 0.71). The univariable analysis showed that chemotherapy with cycles ≥4 presented a better prognosis than with cycles <4 (OS: p = 0.01; HR = 6.71; PFS: p = 0.02; HR = 5.18). The multivariate analysis indicated that the cycles of chemotherapy (p = 0.02; HR 0.29) were a prognostic factor for PFS. LIMITATIONS: A retrospective design and the absence of partial follow-up data are limitations of the study. CONCLUSIONS: In initially surgically treated HG-NECC, postoperative chemotherapy alone showed no inferiority when compared with chemoradiotherapy for HG-NECC, and 4+ cycles of chemotherapy tended to produce a better prognosis than 4-ones.

Co-expression of the SARS-CoV-2 entry molecules ACE2 and TMPRSS2 in human ovaries: Identification of cell types and trends with age.

The high rate of SARS-CoV-2 infection poses a serious threat to public health. Previous studies have suggested that SARS-CoV-2 can infect human ovary, the core organ of the female reproductive system. However, it remains unclear which type of ovarian cells are easily infected by SARS-CoV-2 and whether ovarian infectivity differs from puberty to menopause. In this study, public datasets containing bulk and single-cell RNA-Seq data derived from ovarian tissues were analyzed to demonstrate the mRNA expression and protein distribution of the two key entry receptors for SARS-CoV-2-angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2). Furthermore, an immunohistochemical study of ACE2 and TMPRSS2 in human ovaries of different ages was conducted. Differentially expressed gene (DEG) analysis of ovaries of different ages and with varying ovarian reserves was conducted to explore the potential functions of ACE2 and TMPRSS2 in the ovary. The analysis of the public datasets indicated that the co-expression of ACE2 and TMPRSS2 was observed mostly in oocytes and partially in granulosa cells. However, no marked difference was observed in ACE2 or TMPRSS2 expression between young and old ovaries and ovaries with low and high reserves. Correspondingly, ACE2 and TMPRSS2 were detected in the human ovarian cortex and medulla, especially in oocytes of different stages, with no observed variations in their expression level in ovaries of different ages, which was consistent with the results of bioinformatic analyses. Remarkably, DEG analysis showed that a series of viral infection-related pathways were more enriched in ACE2-positive ovarian cells than in ACE2-negative ovarian cells, suggesting that SARS-CoV-2 may potentially target specific ovarian cells and affect ovarian function. However, further fundamental and clinical research is still needed to monitor the process of SARS-CoV-2 entry into ovarian cells and the long-term effects of SARS-CoV-2 infection on the ovarian function in recovered females.

Potential Influence of Menstrual Status and Sex Hormones on Female Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Cross-sectional Multicenter Study in Wuhan, China.

BACKGROUND: Recent studies have indicated that females with coronavirus disease 2019 (COVID-19) have a lower morbidity, severe case rate, and mortality and better outcome than those of male individuals. However, the reasons remained to be addressed. METHODS: To find the factors that potentially protect females from COVID-19, we recruited all confirmed patients hospitalized at 3 branches of Tongji Hospital (N = 1902), and analyzed the correlation between menstrual status (n = 509, including 68 from Mobile Cabin Hospital), female hormones (n = 78), and cytokines related to immunity and inflammation (n = 263), and the severity/clinical outcomes in female patients <60 years of age. RESULTS: Nonmenopausal female patients had milder severity and better outcome compared with age-matched men (P < .01 for both). Menopausal patients had longer hospitalization times than nonmenopausal patients (hazard ratio [HR], 1.91 [95% confidence interval {CI}, 1.06-3.46]; P = .033). Both anti-Müllerian hormone (AMH) and estradiol (E2) showed a negative correlation with severity of infection (adjusted HR, 0.146 [95% CI, .026-.824], P = .029 and 0.304 [95% CI, .092-1.001], P = .05, respectively). E2 levels were negatively correlated with interleukin (IL) 2R, IL-6, IL-8, and tumor necrosis factor alpha in the luteal phase (P = .033, P = .048, P = .054, and P = .023) and C3 in the follicular phase (P = .030). CONCLUSIONS: Menopause is an independent risk factor for female COVID-19 patients. AMH and E2 are potential protective factors, negatively correlated with COVID-19 severity, among which E2 is attributed to its regulation of cytokines related to immunity and inflammation.

Proteomic analysis of mouse ovaries during the prepubertal stages.

Postnatal folliculogenesis, primordial follicle activation and follicular development at early stage are important for normal ovarian function and fertility, and a comprehensive understanding of this process under physiological condition is necessary. To observe the regulation and mechanism of ovarian follicle development during the prepubertal stages, we collected the mouse ovaries from three time points, including 1 day, 7 days, and 4 weeks after birth. We then performed a proteomic analysis using tandem mass tags (TMT) labeling combined with a two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) technique. A total of 706 proteins were determined to be significant differential abundance (P-SDA). Sixty upregulated proteins and 12 downregulated proteins that were P-SDA and 3 significant KEGG pathways (P < 0.05) were found at 7 days vs. 1 day after birth, while 237 upregulated proteins, 271 downregulated proteins and 42 significant KEGG pathways were found for 4 weeks vs. 7 days after birth. Some vital genes (Figla, Ooep, Padi6, Zp3, Hsd3b1, cyp11a1), key pathways (ECM-receptor interaction, focal adhesion, ovarian steroidogenesis, complement and coagulation cascades, PI3K/Akt/mTOR), and metabolic regulation (energy metabolism, lipid metabolism, metal ion metabolism) were found to be related to the postnatal folliculogenesis, primordial follicle activation and follicular development. Finally, qRT-PCR and western blotting verified some vital genes and further elucidated the developmental process of follicles, and the results may contribute to the understanding of the formation and activation of primordial follicle and follicular development. Significance: This study offers the first proteomic insights into mechanisms of follicle development under physiological condition during the prepubertal stages. By comparing P-SDA of mouse ovaries during various period of age, our data reveals that the regulation of primordial follicle formation and activation is significantly different from that of follicular development. These findings demonstrate that many unique molecular mechanisms underlie ovarian development could be used for ovarian disease research.

Slanted Ag-Al alloy nanorods arrays for highly active and stable surface-enhanced Raman scattering substrates.

Aluminum has been established as an earth-abundant and low-cost alternative to gold and silver for plasmonic applications. Particularly, aluminum largely tends to combines with oxygen compared with silver. Here, a simple glancing angle deposition technique is presented to prepare Ag-Al alloy nanorods (NRs) with a small amount of aluminum. The effect of aluminum is to combine oxygen or corroded substances under certain conditions, such as in the air and in etchants. Beside this, owing to the large diffusion coefficient of aluminum in a Si wafer, the aluminum diffuses easily into a Si wafer, so the bonding force between the Ag-Al alloy NRs and Si wafer can be improved accordingly. In this work, 3.5 at% Al alloy NRs are optimal to exhibit high surface-enhanced Raman scattering (SERS) sensitivity, long-time stability as well as strong bonding force with a Si wafer. Ag-Al alloy NRs make a metal-metal alloy a promising material platform to develop pretty sensitive as well as stable SERS substrates.

Standing wave type localized surface plasmon resonance of multifold Ag nanorods.

Multifold Ag nanorods (AgNRs) have demonstrated great potentials in applications such as surface-enhanced Raman scattering technique due to their specially organized nanostructures. However, there is so far no systematic understanding of their localized surface plasmon resonance (LSPR) behaviors. This work comprehensively studied the plasmonic behaviors of AgNRs with 1, 2 and 3 folded arms. LSPR modes with charge oscillations resembling standing waves were excited in all nanostructures. As arm length increases, there were linear relationships between resonance wavelength and arm length, which applied to all LSPR modes studied. In addition, directly proportional relationships between the slopes of the linear functions and arm number were found for same order LSPR modes of AgNRs. For different modes of a specific AgNR, inversely proportional relationships between the slope and the resonance order N were discovered. These findings evidenced AgNR's standing wave type LSPR characteristics.

Enrichment of Female Germline Stem Cells from Mouse Ovaries Using the Differential Adhesion Method.

BACKGROUND/AIMS: The isolation and establishment of female germline stem cells (FGSCs) is controversial because of questions regarding the reliability and stability of the isolation method using antibody targeting mouse vasa homologue (MVH), and the molecular mechanism of FGSCs self-renewal remains unclear. Thus, there needs to be a simple and reliable method for sorting FGSCs to study them. METHODS: We applied the differential adhesion method to enrich FGSCs (DA-FGSCs) from mouse ovaries. Through four rounds of purification and 7-9 subsequent passages, DA-FGSC lines were established. In addition, we assessed the role of the phosphoinositide-3 kinase (PI3K)-AKT pathway in regulating FGSC self-renewal. RESULTS: The obtained DA-FGSCs spontaneously differentiated into oocyte-like cells in vitro and formed functional eggs in vivo that were fertilized and produced healthy offspring. AKT was rapidly phosphorylated when the proliferation rate of FGSCs increased after 10 passages, and the addition of a chemical PI3K inhibitor prevented FGSCs self-renewal. Furthermore, over-expression of AKT-induced proliferation and differentiation of FGSCs, c-Myc, Oct-4 and Gdf-9 levels were increased. CONCLUSIONS: The differential adhesion method provides a more feasible approach and is an easier procedure to establish FGSC lines than traditional methods. The AKT pathway plays an important role in regulation of the proliferation and maintenance of FGSCs. These findings could help promote stem cell studies and provide a better understanding of causes of ovarian infertility, thereby providing potential treatments for infertility.

Fabrication and simulation of V-shaped Ag nanorods as high-performance SERS substrates.

Bending straight Ag nanorods (AgNRs) into V-shaped structures can generate a higher surface-enhanced Raman scattering (SERS) performance. Numerical simulations showed that V-shaped AgNRs with a total length between 300 nm and 800 nm were more sensitive than equal-length straight AgNRs under a 785 nm laser in most cases. It was found that at a laser wavelength between 500 nm and 1000 nm, the Raman enhancement factor (EF) of a V-shaped AgNR's 3rd plasmon mode was not only optimal among the other major plasmon modes, but also outperformed the plasmon modes of straight AgNRs. Besides, a linear relationship between the resonance wavelength of the V-shaped AgNR's 3rd mode and its length was observed both numerically and experimentally, which was beneficial for the optimization of SERS substrates. Under 785 nm laser excitation, V-shaped AgNR substrates with a single arm length between 330 nm and 340 nm possessed the highest SERS efficiency. This work took AgNR array substrates one step closer to practical applications.

Design of Ag nanorods for sensitivity and thermal stability of surface-enhanced Raman scattering.

The technology of surface-enhanced Raman scattering (SERS) has found many applications and may find more if it can possess both sensitivity and thermal stability. This paper reports a rational design of Ag nanorods to simultaneously achieve two competing goals: the sensitivity and the thermal stability of SERS substrates. The Ag nanorods are designed and synthesized using physical vapor deposition under the condition of glancing angle incidence. The working pressure of the vacuum chamber is controlled so the mean free path of depositing atoms is comparable to the dimension of the chamber, so as to grow Ag nanorods with small diameter, and small but clear separation for optimal SERS sensitivity. Such Ag nanorods are further capped with Al2O3 on their top surfaces to reduce the diffusion-induced coarsening at high temperatures, and thereby to improve the thermal stability for SERS detections. Meanwhile, since the side surfaces of Ag nanorods are not coated with oxides in this approach, the SERS sensitivity is largely preserved while good thermal stability is achieved.

Nanoparticle-on-mirror cavity modes for huge and/or tunable plasmonic field enhancement.

We present a careful numerical study of nanoparticle (NP) faceting, highlighting the great influence of small morphological changes of NP-mirror cavities on near-field enhancement in the nanoparticle-on-mirror (NPOM) system. Using a 3D finite element method (FEM) plasmon mapping method, the active transverse cavity modes can be confirmed. For the dominant mode, we have found that, by increasing the facet width, the resonance can be tuned linearly to the red with little decrease of the peak near-field intensity. It is further demonstrated that by increasing the NP size, the near-field intensity can be strongly enhanced. Understanding of such extreme optics benefits significantly both the optimized design of potential plasmonic devices and the fundamental understanding of nano-optics. Collaborative experimental considerations are expected with the rapid development of nanotechnology.

Ag Nanorods-Oxide Hybrid Array Substrates: Synthesis, Characterization, and Applications in Surface-Enhanced Raman Scattering.

Over the last few decades, benefitting from the sufficient sensitivity, high specificity, nondestructive, and rapid detection capability of the surface-enhanced Raman scattering (SERS) technique, numerous nanostructures have been elaborately designed and successfully synthesized as high-performance SERS substrates, which have been extensively exploited for the identification of chemical and biological analytes. Among these, Ag nanorods coated with thin metal oxide layers (AgNRs-oxide hybrid array substrates) featuring many outstanding advantages have been proposed as fascinating SERS substrates, and are of particular research interest. The present review provides a systematic overview towards the representative achievements of AgNRs-oxide hybrid array substrates for SERS applications from diverse perspectives, so as to promote the realization of real-world SERS sensors. First, various fabrication approaches of AgNRs-oxide nanostructures are introduced, which are followed by a discussion on the novel merits of AgNRs-oxide arrays, such as superior SERS sensitivity and reproducibility, high thermal stability, long-term activity in air, corrosion resistivity, and intense chemisorption of target molecules. Next, we present recent advances of AgNRs-oxide substrates in terms of practical applications. Intriguingly, the recyclability, qualitative and quantitative analyses, as well as vapor-phase molecule sensing have been achieved on these nanocomposites. We further discuss the major challenges and prospects of AgNRs-oxide substrates for future SERS developments, aiming to expand the versatility of SERS technique.

Gradual plasmon evolution and huge infrared near-field enhancement of metallic bridged nanoparticle dimers.

By three-dimensional (3D) finite element method (FEM) plasmon mapping, gradual plasmon evolutions of both bonding dipole plasmon (BDP) and charge transfer plasmon (CTP) modes are visualized. In particular, the evolved BDP mode provides a physical insight into the rapid degeneration of electromagnetic hot spots in practical applications, while the rising CTP mode enables a huge near-field enhancement for potential plasmonic devices at infrared wavelengths.

Nanogap effects on near- and far-field plasmonic behaviors of metallic nanoparticle dimers.

In the field of plasmonics, the nanogap effect is often related to one aspect like the near-field enhancement at a single excitation wavelength or the far-field resonance shift. In this study, taking full advantage of finite element method (FEM) calculations, we present a comprehensive and quantitative analysis of the nanogap effect on the plasmonic behaviors of metallic nanoparticle dimers. Firstly, near-field spectroscopy is proposed in order to extract the near-field resonance wavelengths. Focusing on the bonding dipole mode, it is found that the near-field enhancement factors exhibit a weak power-law dependence on the gap size, while the near-field resonance shift decays nearly exponentially as the gap size increases, with a lower decay length than that for the far-field resonance shift. The spectral deviation between these two shifts is suggested to be taken into account for spectroscopy applications of plasmonic devices, although it may be negligible for dimer structures with rather small gaps.

Control of Hybrid Exciton Lifetime in MoSe2/WS2 Moiré Heterostructures.

Hybrid excitons, characterized by their strong oscillation strength and long lifetimes, hold great potential as information carriers in semiconductors. They offer promising applications in exciton-based devices and circuits. MoSe2/WS2 heterostructures represent an ideal platform for studying hybrid excitons, but how to regulate the exciton lifetime has not yet been explored. In this study, layer hybridization is modulated by applying electric fields parallel or antiparallel to the dipole moment, enabling us to regulate the exciton lifetime from 1.36 to 4.60 ns. Furthermore, the time-resolved photoluminescence decay traces are measured at different excitation power. A hybrid exciton annihilation rate of 8.9 × 10-4 cm2 s-1 is obtained by fitting. This work reveals the effects of electric fields and excitation power on the lifetime of hybrid excitons in MoSe2/WS2 1.5° moiré heterostructures, which play important roles in high photoluminescence quantum yield optoelectronic devices based on transition-metal dichalcogenides heterostructures.

A Review of Trends in Corrosion-Resistant Structural Steels Research-From Theoretical Simulation to Data-Driven Directions.

This paper provides a review of models commonly used over the years in the study of microscopic models of material corrosion mechanisms, data mining methods and the corrosion-resistant performance control of structural steels. The virtual process of material corrosion is combined with experimental data to reflect the microscopic mechanism of material corrosion from a nano-scale to macro-scale, respectively. Data mining methods focus on predicting and modeling the corrosion rate and corrosion life of materials. Data-driven control of the corrosion resistance of structural steels is achieved through micro-alloying and organization structure control technology. Corrosion modeling has been used to assess the effects of alloying elements, grain size and organization purity on corrosion resistance, and to determine the contents of alloying elements.

Current Animal Model Systems for Ovarian Aging Research.

Ovarian aging leads to menopause, loss of fertility and other disorders in multiple organs, which brings great distress to women. For ethical reasons, it is impossible to use humans as direct study subjects for aging research. Therefore, biomedical researchers have employed different non-human organisms to study ovarian aging, including worms, fruit flies, fishes, amphibians, birds, mice, rats, cavies, rabbits, pigs, sheep, cows, horses, monkeys, and apes. Because each of these model organisms has its own features, multiple factors, such as size, anatomical structure, cost, ease of operation, fertility, generation time, lifespan, and gene heredity, should be carefully considered when selecting a model system to study ovarian aging. An appropriate model organism would help researchers explore the risk factors and elucidate molecular mechanisms underlying declined ovarian functions, which might be conducive to preventing or delaying the ovarian aging process. This article will offer an overview on several currently available and commonly used model organisms for ovarian aging research by comparing their pros and cons. In doing so, we hope to provide useful information for ovarian aging researchers.

Microbiologically influenced corrosion inhibition mechanisms in corrosion protection: A review.

Microbial activities can change the properties of biofilm/metal interfaces to accelerate or decelerate the corrosion of metals in a given environment. Microbiologically influenced corrosion inhibition (MICI) is the inhibition of corrosion that is directly or indirectly induced by microbial action. Compared with conventional methods for protection from corrosion, MICI is environmentally friendly and an emerging approach for the prevention and treatment of (bio)corrosion. However, due to the diversity of microorganisms and the fact that their metabolic processes are greatly complicated by environmental factors, MICI is still facing challenges for practical application. This review provides a comprehensive overview of the mechanisms of MICI under different conditions and their advantages and disadvantages for potential applications in corrosion protection.

Identification of Key Genes and Potential New Biomarkers for Ovarian Aging: A Study Based on RNA-Sequencing Data.

Ovarian aging leads to reproductive and endocrine dysfunction, causing the disorder of multiple organs in the body and even declined quality of offspring's health. However, few studies have investigated the changes in gene expression profile in the ovarian aging process. Here, we applied integrated bioinformatics to screen, identify, and validate the critical pathogenic genes involved in ovarian aging and uncover potential molecular mechanisms. The expression profiles of GSE84078 were downloaded from the Gene Expression Omnibus (GEO) database, which included the data from ovarian samples of 10 normal C57BL/6 mice, including old (21-22 months old, ovarian failure period) and young (5-6 months old, reproductive bloom period) ovaries. First, we filtered 931 differentially expressed genes (DEGs), including 876 upregulated and 55 downregulated genes through comparison between ovarian expression data from old and young mice. Functional enrichment analysis showed that biological functions of DEGs were primarily immune response regulation, cell-cell adhesion, and phagosome pathway. The most closely related genes among DEGs (Tyrobp, Rac2, Cd14, Zap70, Lcp2, Itgb2, H2-Ab1, and Fcer1g) were identified by constructing a protein-protein interaction (PPI) network and consequently verified using mRNA and protein quantitative detection. Finally, the immune cell infiltration in the ovarian aging process was also evaluated by applying CIBERSORT, and a correlation analysis between hub genes and immune cell type was also performed. The results suggested that plasma cells and naïve CD4+ T cells may participate in ovarian aging. The hub genes were positively correlated with memory B cells, plasma cells, M1 macrophages, Th17 cells, and immature dendritic cells. In conclusion, this study indicates that screening for DEGs and pathways in ovarian aging using bioinformatic analysis could provide potential clues for researchers to unveil the molecular mechanism underlying ovarian aging. These results could be of clinical significance and provide effective molecular targets for the treatment of ovarian aging.

Ag Nanorods-Based Surface-Enhanced Raman Scattering: Synthesis, Quantitative Analysis Strategies, and Applications.

Surface-Enhanced Raman Scattering (SERS) is a powerful technology that provides abundant chemical fingerprint information with advantages of high sensitivity and time-saving. Advancements in SERS substrates fabrication allow Ag nanorods (AgNRs) possess superior sensitivity, high uniformity, and excellent reproducibility. To further promote AgNRs as a promising SERS substrate candidate to a broader application scope, oxides are integrated with AgNRs by virtue of their unique properties which endow the AgNRs-oxide hybrid with high stability and recyclability. Aside from SERS substrates fabrication, significant developments in quantitative analysis strategies offer enormous approaches to minimize influences resulted from variations of measuring conditions and to provide the reasonable data analysis. In this review, we discuss various fabrication approaches for AgNRs and AgNRs-oxide hybrids to achieve efficient SERS platforms. Then, we introduce three types of strategies which are commonly employed in chemical quantitative analysis to reach a reliable result. Further, we highlight SERS applications including food safety, environment safety, biosensing, and vapor sensing, demonstrating the potential of SERS as a powerful and promising technique. Finally, we conclude with the current challenges and future prospects toward efficient SERS manipulations for broader real-world applications.