Recryopreservation impairs blastocyst implantation potential via activated endoplasmic reticulum stress pathway and induced apoptosis.

Recryopreservation (recryo) is occasionally applied in clinical, while the underlying mechanism of impaired clinical outcomes after recryo remains unclear. In this study, frozen embryo transfer (FET) cycles of single blastocyst transfer in an academic reproductive medicine center were enrolled. According to the number of times blastocysts experienced cryopreservation, they were divided into the cryopreservation (Cryo) group and the Recryo group. Donated human blastocysts were collected and detected for mechanism exploration. It was found that recryo procedure resulted in impaired blastocyst developmental potential, including decreased implantation rate, reduced biochemical pregnancy rate, declined clinical pregnancy rate, higher early miscarriage rate, and lower live birth rate. Moreover, recryo led to impaired trophectoderm (TE) function, exhibiting lower human chorionic gonadotropin levels 12 days after FET. In addition, single-cell RNA sequencing showed that the expression of genes involved in cell adhesion and embryo development were altered. More specifically, activated endoplasmic reticulum (ER) pathway and induced apoptosis were further verified by immunofluorescence and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay involving in the recryo procedure. In conclusion, recryo could interfere with the process of blastocyst implantation by impairing TE function, affecting blastocyst adhesion, activating ER stress pathway and inducing apoptosis. It provides caution to embryologists about the potential risk of recryopreservation.

Distinct functions of microtubules and actin filaments in the transportation of the male germ unit in pollen.

Flowering plants rely on the polarized growth of pollen tubes to deliver sperm cells (SCs) to the embryo sac for double fertilization. In pollen, the vegetative nucleus (VN) and two SCs form the male germ unit (MGU). However, the mechanism underlying directional transportation of MGU is not well understood. In this study, we provide the first full picture of the dynamic interplay among microtubules, actin filaments, and MGU during pollen germination and tube growth. Depolymerization of microtubules and inhibition of kinesin activity result in an increased velocity and magnified amplitude of VN's forward and backward movement. Pharmacological washout experiments further suggest that microtubules participate in coordinating the directional movement of MGU. In contrast, suppression of the actomyosin system leads to a reduced velocity of VN mobility but without a moving pattern change. Moreover, detailed observation shows that the direction and velocity of VN's movement are in close correlations with those of the actomyosin-driven cytoplasmic streaming surrounding VN. Therefore, we propose that while actomyosin-based cytoplasmic streaming influences on the oscillational movement of MGU, microtubules and kinesins avoid MGU drifting with the cytoplasmic streaming and act as the major regulator for fine-tuning the proper positioning and directional migration of MGU in pollen.

Understanding the Resistive Switching Behaviors of Top Electrode (Au, Cu, and Al)-Dependent TiO2-Based Memristive Devices.

Memristor-based neuromorphic computing is promising toward their potential application of handling complex parallel tasks in the period of big data. To implement brain-inspired applications of spiking neural networks, new physical architecture designs are needed. Here, a serial memristive structure (SMS) consisting of memristive devices with different top electrodes is proposed. Top electrodes Au, Cu, and Al are selected for nitrogen-doped TiO2 nanorod array-based memristive devices. The typical I-V cycles, retention, on/off ratio, and variations of cycle to cycle of top electrode-dependent memristive devices have been studied. Devices with Cu and Al electrodes exhibit a retention of over 104 s. And the resistance states of the device with the Al top electrode are reliable. Furthermore, the conductive mechanism underlining the I-V curves is discussed in detail. The interface-type mechanism and block conductance mechanism are illustrated, which are related to electron migration and ion/anion migration, respectively. Finally, the SMS has been constructed using memristive devices with Al and Cu top electrodes, which can mimic the spiking pulse-dependent plasticity of a synapse and a neuron body. The SMS provides a new approach to implement a fundamental physical unit for neuromorphic computing.

A new insight on evaluation of the fertility and pregnancy outcome in patients with primary Sjögren syndrome: a propensity score matched study in multi-IVF centers.

BACKGROUND: Primary Sjögren syndrome (pSS) is often related to adverse neonatal outcomes. But it's currently controversial whether pSS has an adverse effect on female fertility and clinical pregnancy condition. More importantly, it's unclear regarding the role of pSS in oocyte and embryonic development. There is a lack of comprehensive understanding and evaluation of fertility in pSS patients. OBJECTIVE: This study aimed to investigate oocyte and embryonic development, ovarian reserve, and clinical pregnancy outcomes in Primary Sjögren syndrome (pSS) patients during in vitro fertilization (IVF) treatment from multi-IVF centers. METHODS: We performed a muti-central retrospective cohort study overall evaluating the baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical pregnancy outcomes between the pSS patients and control patients who were matched by Propensity Score Matching. RESULTS: Following PSM matching, baseline characteristics generally coincided between the two groups. Ovarian reserve including anti-müllerian hormone (AMH) and antral follicle counting (AFC) were significantly lower in the pSS group vs comparison (0.8 vs. 2.9 ng/mL, P < 0.001; 6.0 vs. 10.0, P < 0.001, respectively). The pSS group performed significant reductions in numbers of large follicles, oocytes retrieved and MII oocytes. Additionally, pSS patients exhibited obviously deteriorate rates of oocyte maturation, 2PN cleavage, D3 good-quality embryo, and blastocyst formation compared to comparison. As for clinical pregnancy, notable decrease was found in implantation rate (37.9% vs. 54.9%, P = 0.022). The cumulative live birth rate (CLBR) following every embryo-transfer procedure was distinctly lower in the pSS group, and the conservative and optimal CLBRs following every complete cycle procedure were also significantly reduced in the pSS group. Lastly, the gestational weeks of the newborns in pSS group were distinctly early vs comparison. CONCLUSION: Patients with pSS exhibit worse conditions in terms of female fertility and clinical pregnancy, notably accompanied with deteriorate oocyte and embryo development. Individualized fertility evaluation and early fertility guidance are essential for these special patients.

Blocking H1R signal aggravates atherosclerosis by promoting inflammation and foam cell formation.

Atherosclerosis (AS) is a chronic inflammatory arterial disease, in which abnormal lipid metabolism and foam cell formation play key roles. Histamine is a vital biogenic amine catalyzed by histidine decarboxylase (HDC) from L-histidine. Histamine H1 receptor (H1R) antagonist is a commonly encountered anti-allergic agent in the clinic. However, the role and mechanism of H1R in atherosclerosis have not been fully elucidated. Here, we explored the effect of H1R on atherosclerosis using Apolipoprotein E-knockout (ApoE-/-) mice with astemizole (AST, a long-acting H1R antagonist) treatment. The results showed that AST increased atherosclerotic plaque area and hepatic lipid accumulation in mice. The result of microarray study identified a significant change of endothelial lipase (LIPG) in CD11b+ myeloid cells derived from HDC-knockout (HDC-/-) mice compared to WT mice. Blocking H1R promoted the formation of foam cells from bone marrow-derived macrophages (BMDMs) of mice by up-regulating p38 mitogen-activated protein kinase (p38 MAPK) and LIPG signaling pathway. Taken together, these findings demonstrate that blocking H1R signal aggravates atherosclerosis by promoting abnormal lipid metabolism and macrophage-derived foam cell formation via p38 MAPK-LIPG signaling pathway. KEY MESSAGES: Blocking H1R signal with AST aggravated atherosclerosis and increased hepatic lipid accumulation in high-fat diet (HFD)-fed ApoE-/- mice. Blocking H1R signal promoted macrophage-derived foam cell formation via p38 MAPK-LIPG signaling pathway.

Spatiotemporal distribution of ecological risk of antibiotics in seven major river basins of China: An optimized multilevel assessment approach.

Antibiotics have been recognized as emerging pollutants due to their ecological and human health risks. This paper aims to enhance the ecological risk assessment (ERA) framework for antibiotics, to illustrate the distribution of these risks across different locations and seasons, and to identify the antibiotics that pose high ecological risk. This paper focuses on 52 antibiotics in seven major basins of China. Relying on the optimized approach of ERA and antibiotic monitoring data published from 2017 to 2021, the results of ERA are presented in multilevel. Across the study area, there are marked variations in the spatial distribution of antibiotics' ecological risks. The Huaihe River Basin, the Haihe River Basin, and the Liaohe River Basin are the top three in the ranking of present ecological risks. The research results also reveal significant differences in temporal variation, underscoring the need for increased attention during certain seasons. Ten antibiotics with high contribution rates to ecological risk are identified, which is an important reference to formulate an antibiotic control list. The multilevel results provided both risk values and their ubiquities across a broad study region, which is a powerful support for developing ecological risk management of antibiotics.

The genetic relationship between systemic lupus erythematosus and risk of primary ovarian failure from a mendelian randomization study.

Previous studies investigating the relationship between systemic lupus erythematosus (SLE) and primary ovarian failure (POF) generated conflicting results. To data, no mendelian randomization study has been applied to examine this association. In this study, genetic instruments for exposure (SLE) were selected from a GWAS study with 5201 cases and 9066 noncases. Outcome data for POF and three reproductive traits (age at menarche, age at menopause, and age at first live birth) were obtained from other eligible GWASs. To estimate causal association, the inverse-variance weighted (IVW) method (the main analyse), MR Egger test, weighted median, simple mode, and weighted mode were applied. Moreover, sensitivity analyses were conducted to ensure the robustness of the results. Estimated by the IVW method, SLE was suggested to be causally related to the risk of POF (OR = 1.166, 95% CI 1.055-1.289, P = 0.003) and delayed age at first live birth (OR = 1.006, 95% CI 1.002-1.010, P = 0.007), with no evidence of a causal association between SLE and age at menopause or menarche. The estimates were robust according to sensitivity analysis. In conclusion, the two-sample MR study supported a causal association between SLE and POF from a genetic aspect.

Photo-excited charge transfer from adamantane to electronic bound states in water.

Aqueous nanodiamonds illuminated by UV light produce free solvated electrons, which may drive high-energy reduction reactions in water. However, the influence of water conformations on the excited-state electron-transfer mechanism are still under debate. In this work, we offer a theoretical study of charge-transfer states in adamantane-water structures obtained by linear-response time-dependent density-functional theory. Small water clusters with broken hydrogen bonds are found to efficiently bind the electron from adamantane. A distinction is made with respect to the nature of the water clusters: some bind the electron in a water cavity, others along a strong permanent total dipole. These two types of bound states are more strongly binding, the higher their electron affinity and their positive electrostatic potential, the latter being dominated by the energy of the lowest unoccupied molecular orbital of the isolated water clusters. Structural sampling in a thermal equilibrium at room temperature via molecular dynamics snapshots confirms under which conditions the underlying waters clusters can occur and verifies that broken hydrogen bonds in the water network close to adamantane can create traps for the solvated electron.

An overview of CFTR mutation profiles and assisted reproductive technology outcomes in Chinese patients with congenital obstructive azoospermia.

PURPOSE: The cystic fibrosis transmembrane conductance regulator (CFTR) is the most common causative gene attributed to congenital obstructive azoospermia (OA). The aim of this study was to conduct an epidemiological survey of congenital OA patients, to screen for CFTR mutations, and to follow their pregnancy outcomes in assisted reproductive technology (ART). METHODS: This cohort study enrolled congenital OA patients undergoing ART and whole-exome sequencing from January 2018 to September 2023. Semen parameters, sex hormones, and seminal plasma biochemistry were evaluated. CFTR mutations identified in OA patients were analyzed. In addition, the laboratory outcomes, clinical outcomes, and neonatal outcomes were compared between OA patients carrying two CFTR mutations and the others after surgical sperm extraction-intracytoplasmic sperm injection (ICSI) treatment. RESULTS: A total of 76 patients with congenital OA were enrolled. CFTR mutations were identified in 35 (46.1%) congenital OA patients. A total of 60 CFTR mutation sites of 27 types were identified, and 10 of them were novel. The average frequency was 1.71 (60/35) per person. The most common mutation was c.1210-11T > G (25%, 15/60). After ICSI treatment, there were no statistically significant differences in laboratory outcomes, clinical outcomes, and neonatal outcomes between OA patients carrying two CFTR mutations (n = 25) and other OA patients (n = 51). CONCLUSION: Apart from the IVS9-5T mutation, the genetic mutation pattern of CFTR in Chinese OA patients is heterogeneous, which is significantly different from that of Caucasians. Although carrying two CFTR mutations or not had no effect on the pregnancy outcomes in OA patients after ICSI, genetic counseling is still recommended for such patients.

Ground and excited state charge transfer at aqueous nanodiamonds.

Nanodiamonds (NDs) are unique carbonaceous materials with exceptionally high stability, hardness, and notable electronic properties. Their applications in photocatalysis, biomedicine, and energy materials are usually carried out in aqueous environments, where they interact with aqueous adsorbates. Especially, electron density may rearrange from the diamond material toward oxidative adsorbates such as oxygen, which is known as charge transfer doping. In this article, we quantify the charge transfer doping for NDs with inhomogeneous surface coverings (hydroxyl, fluorine, and amorphous carbon), as well as NDs doped with heteroatoms (B, Si, N) using hybrid density functional theory (DFT) calculations. The transfer doping magnitude is largely determined by the NDs' highest occupied molecular orbital energies, which can in turn be modified by the surface covering and doping. However, local modifications of the ND structures do not have any local effects on the magnitude of the charge transfer. We furthermore analyze the impact of aqueous adsorbates on the excited states of an aqueous ND in the context of photocatalysis via time-dependent DFT. Here, we find that the excited electrons are biased to move in the direction of the respective oxidative adsorbate. Surprisingly, we find that also unreactive species such as nitrous oxide may attract the excited electrons, which is probably due to the positive partial charge that is induced by the local N 2 O solvation geometry.