A bipolar organic molecule towards the anion/cation-hosting cathode compatible with polymer electrolytes for quasi-solid-state dual-ion batteries.

Ion concentration and mobility are tightly associated with the ionic conductance of polymer electrolytes in solid-state lithium batteries. However, the anions involved in the movement are irrelevant to energy generation and cause uncontrolled dendritic growth and concentration polarization. In the current study, we proposed the strategy of using a bipolar organic molecule as the anion/cation-hosting cathode to expand the active charge carriers of polymer electrolytes. As a proof-of-concept demonstration of the novel strategy, a bipolar phthalocyanine derivative (2,3,9,10,16,17,23,24-octamethoxyphthalocyaninato) Ni(II) (NiPc-(OH)8) that could successively store anions and cations was used as the cathode hosting material in quasi-solid-state dual-ion batteries (QSSDIBs). Interestingly, peripheral polyhydroxyl substituents could build a compatible interface with poly(vinylidene fluoride-hexafluoro propylene-based gel polymer electrolytes (PVDF-HFP). As expected, NiPc-(OH)8 displays a high specific capacity of 248.2 mAh/g (at 50 mA g-1) and improved cyclic stability compared with that in liquid electrolyte. This study provides a solution to the issue of anion migration and could open another way to build high-performance QSSDIBs.

Gestational exposure to 1-NP induces ferroptosis in placental trophoblasts via CYP1B1/ERK signaling pathway leading to fetal growth restriction.

Fetal growth restriction (FGR) is a prevalent complication in obstetrics, yet its exact aetiology remains unknown. Numerous studies suggest that the degradation of the living environment is a significant risk factor for FGR. 1-Nitropyrene (1-NP) is a widespread environmental pollutant as a representative substance of nitro-polycyclic aromatic hydrocarbons. In this study, we revealed that 1-NP induced FGR in fetal mice by constructing 1-NP exposed pregnant mice models. Intriguingly, we found that placental trophoblasts of 1-NP exposed mice exhibited significant ferroptosis, which was similarly detected in placental trophoblasts from human FGR patients. In this regard, we established a 1-NP exposed cell model in vitro using two human trophoblast cell lines, HTR8/SVneo and JEG-3. We found that 1-NP not only impaired the proliferation, migration, invasion and angiogenesis of trophoblasts, but also induced severe cellular ferroptosis. Meanwhile, the ferroptosis inhibitor ferrostatin-1 (Fer-1) effectively rescued 1-NP-induced trophoblast biological function impairment. Mechanistically, we revealed that 1-NP regulated ferroptosis by activating the ERK signaling pathway. Moreover, we innovatively revealed that CYP1B1 was essential for the activation of ERK signaling pathway induced by 1-NP. Overall, our study innovatively identified ferroptosis as a significant contributor to 1-NP induced trophoblastic functional impairment leading to FGR and clarified the specific mechanism by which 1-NP induced ferroptosis via the CYP1B1/ERK signaling pathway. Our study provided novel insights into the aetiology of FGR and revealed new mechanisms of reproductive toxicity of environmental pollutants.

Isolation and functional identification of immune cells in hemolymph of blood clams Tegillarca granosa.

Blood clam Tegillarca granosa is a type of economically cultivated bivalve mollusk with red blood, and it primarily relies on hemocytes in its hemolymph for immune defense. However, there are currently no reports on the isolation and identification of immune cells in T. granosa, which hinders our understanding of their immune defense. In this study, we employed single-cell transcriptome sequencing (scRNA-seq) to visualize the molecular profile of hemocytes in T. granosa. Based on differential expression of immune genes and hemoglobin genes, hemocytes can be molecularly classified into immune cells and erythrocytes. In addition, we separated immune cells using density gradient centrifugation and demonstrated their stronger phagocytic capacity compared to erythrocytes, as well as higher levels of ROS and NO. In summary, our experiments involved the isolation and functional identification of immune cells in hemolymph of T. granosa. This study will provide valuable insights into the innate immune system of red-blood mollusks and further deepen the immunological research of mollusks.

6-Gingerol alleviates placental injury in preeclampsia by inhibiting oxidative stress via BNIP3/LC3 signaling-mediated trophoblast mitophagy.

Background and aims: Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality worldwide. Apoptosis of trophoblast cells induced by oxidative stress is a principal reason of placental injury in PE. 6-Gingerol, an antioxidant from ginger, plays an important role in many disease models, but its effect on obstetric diseases has not been elucidated. In this study, we investigated the protective effect of 6-gingerol against placental injury. Methods: In vitro hypoxia/reoxygenation (H/R) model of HTR8/Svneo cells and preeclamptic mice model were established to simulate PE. The effects of 6-Gingerol on PE were evaluated by morphological detection, biochemical analysis, and Western blot. Results: We found that H/R treatment induced cell apoptosis, increased the production of reactive oxygen species, malondialdehyde and lactate dehydrogenase, and decreased superoxide dismutase in trophoblast. In addition, the polarization of mitochondrial membrane potential and the cellular calcium flux were also destroyed under H/R condition, which also activated BCL2-interacting protein 3 (BNIP3) and provoked excessive mitophagy. Importantly, 6-Gingerol reversed these corrosive effects. Furthermore, the placenta damage in PE-like mouse caused by the cell apoptosis, oxidative stress and mitophagy was mitigated by 6-Gingerol. Conclusion: These findings suggest that 6-Gingerol exerts a protective effect against placental injury in PE by reducing oxidative stress and inhibiting excessive mitophagy caused by mitochondrial dysfunction.

Whole exome sequencing reveals novel variants associated with diminished ovarian reserve in young women.

Background: Diminished ovarian reserve is one of the most important causes of female infertility. In the etiology study of DOR, besides age, it is known that chromosomal abnormality, radiotherapy, chemotherapy and ovarian surgery can result in DOR. For young women without obvious risk factors, gene mutation should be considered as a possible cause. However, the specific molecular mechanism of DOR has not been fully elucidated. Methods: In order to explore the pathogenic variants related to DOR, twenty young women under 35 years old affected by DOR without definite factors damaging ovarian reserve were recruited as the research subjects, and five women with normal ovarian reserve were recruited as the control group. Whole exome sequencing was applied as the genomics research tool. Results: As a result, we obtained a set of mutated genes that may be related to DOR, where the missense variant on GPR84 was selected for further study. It is found that GPR84Y370H variant promotes the expression of proinflammatory cytokines (TNF-α, IL12B, IL-1ß) and chemokines (CCL2, CCL5), as well as the activation of NF-κB signaling pathway. Conclusion: In conclusion, GPR84Y370H variant was identified though analysis for WES results of 20 DOR patients. The deleterious variant of GPR84 could be the potential molecular mechanism of non-age-related pathological DOR through its role in promoting inflammation. The findings of this study can be used as a preliminary research basis for the development of early molecular diagnosis and treatment target selection of DOR.

Acute sulfide exposure induces hemocyte toxicity and microbiota dysbiosis in blood clam Tegillarca granosa.

Sulfide are widely accumulated in aquatic environments under anaerobic conditions, which cause health problems of aquatic animals, yet their toxic effects to benthic bivalves are not well understood. We investigated the effects of sulfide on innate immunity of the blood clam Tegillarca granosa. Immunity-related indicators and hemolymph microbiota were investigated in the clams exposed to sulfide (via 10, 100 and 1000 µmol/L of Na2S) over a 7-day period. The results showed that cellular immune responses in T. granosa were affected by exposure to high sulfide concentration (1000 µmol/L Na2S), as indicated by total counts of hemocytes (THC), cell viability, ROS levels and phagocytic activities, suggesting that sulfide stress induces T. granosa more vulnerable to pathogen challenges. In addition, the Na2S-induced stress also reshaped the hemolymph microbial community structure of T. granosa that some original genera decreased, such as Lactobacillus, Desulfovibrio and Akkermansia; some genera increased, such as Vibrio and Pseudoalteromonas in sulfide stress group. Sulfide exposure promoted the proliferation of opportunistic pathogen and reduced the diversity of microbial community in the hemolymph of T. granosa. In summary, sulfide stress had marked hemocytotoxicity, reduced immune-cell activity and increased bacterial infections in the blood clam.

Hysteroscopic resection of type 3 fibroids could improve the pregnancy outcomes in infertile women: a case-control study.

BACKGROUND: Type 3 fibroids are a special subtype of intramural fibroids that are likely to affect the pregnancy outcomes of assisted reproductive techniques. Hysteroscopic resection is a treatment for type 3 fibroids, but there has few study of its efficacy to date. In this study we evaluated the effect of hysteroscopic resection of type 3 fibroids on the pregnancy outcomes in infertile women. METHODS: This retrospective case-control study was conducted from January 1, 2014 to June 30, 2021. Patients who underwent IVF-ICSI in our unit were divided into a type 3 fibroid group and a hysteroscopic myomectomy group. The inclusion criteria for the type 3 fibroid group and the hysteroscopic myomectomy group were as follows: 1) age ≤ 40 years; 2) fibroid diameter or total fibroid diameter > 2.0 cm. The following exclusion criteria were used: 1) oocyte donor treatment cycles and 2) presence of chromosomal abnormalities; 3) history of other uterine surgery; 4) presence of intracavitary lesions, including submucosal fibroids; 5) single fibroid > 5.0 cm; 6) cervical fibroids; 7) unclear ultrasound description of fibroids; 8) preimplantation genetic testing was performed and 9) congenital or acquired uterine malformations. The control group in our study was selected from patients who were treated with IVF only because of fallopian tube factors. According to the age of the type 3 fibroid group and hysteroscopic myomectomy group, random sampling was carried out in the patients between 25 and 47 years of age to determine a control group. The outcomes measured included the average transfer times to live birth, cumulative clinical pregnancy rate, and cumulative live birth rate. RESULTS: A total of 302 cycles were enrolled in our study, including 125 cycles with type 3 fibroids, 122 cycles with hysteroscopic myomectomy, and 139 cycles of control patients. The average transfer times to live birth were significantly higher in the type 3 fibroid group than in the other two groups. The frequency of cumulative live births in the type 3 fibroid group was significantly lower than that in the control group. Compared with the control group, the hysteroscopic myomectomy patients had no statistically significant differences in the cumulative clinical pregnancy rate and cumulative live birth rate. CONCLUSIONS: Type 3 fibroids significantly reduced the cumulative live birth rate of IVF patients. Ultrasound-guided hysteroscopic myomectomy can be used as a treatment for type 3 fibroids and could improve the pregnancy outcomes in infertile women.

Adverse obstetric and perinatal outcomes in 2333 singleton pregnancies conceived after different endometrial preparation protocols: a retrospective study in China.

BACKGROUP: Frozen-thawed embryo transfer is rising worldwide. One adverse effect of programmed frozen embryo transfer (FET) reported in some studies is an increased risk of adverse obstetric and perinatal outcomes. Meanwhile, body mass index (BMI) also has adverse effect on obstetric and perinatal outcomes. In this study, we investigated that the influence of different endometrial preparation protocols on obstetric and perinatal outcomes and the role of BMI in it. METHOD: This retrospective cohort study included 2333 singleton deliveries after frozen-thaw embryo transfer at our centre between 2014 and 2021, including 550 cycles with programmed FET, 1783 cycles with true natural cycle FET (tNC-FET). In further analysis according to BMI grouped by Asian criterion, group A (18.5 kg/m2 ≤ BMI < 24.00 kg/m2) included 1257 subjects, group B (24 kg/m2 ≤ BMI < 28.00 kg/m2) included 503 subjects and group C (BMI ≥ 28 kg/m2) included 573 subjects. Baseline characteristics of the two groups were compared and analyzed. Binary logistic regression analyses were performed to explore the association between obstetric and perinatal outcomes and endometrial preparation protocols. RESULTS: There were no significant differences in the placenta previa, gestational diabetes mellitus(GDM), preterm premature rupture of membranes (PPROM), cesarean section (CS) and macrosomia between the tNC-FET and programmed FET groups (P > 0.05). The programmed FET cycles were associated to a higher risk of pregnancy-induced hypertension (PIH) compared with the tNC-FET cycles (7.3% vs 4.4%, crude OR 1.71[1.16-2.54]; adjusted OR 1.845[1.03-3.30]). After dividing the patients into three groups according to the BMI, The programmed FET cycles were associated to a higher risk of PIH in group C (14.4% vs 6.2%, crude OR 2.55 [1.42-4.55]; adjusted OR 4.71 [1.77-12.55]) compared with the tNC-FET cycles. But there was no statistically significant difference in group A and group B. Programmed FET group compared with the tNC-FET group, the risk of PIH increase as the body mass index increase. CONCLUSION: This study showed a tendency toward increasing risk of PIH in programmed FET cycle compared with the tNC-FET cycle, and the risk of PIH increases as BMI increases. Increased risk of preterm birth and low birth weight is linked to increased risk of PIH.

Interleukin-4 activates the PI3K/AKT signaling to promote apoptosis and inhibit the proliferation of granulosa cells.

The inflammatory microenvironment has been demonstrated to play a role in folliculogenesis, ovulation and premature ovarian failure (POF), as well as infertility. In this study, we aimed to explore the role of inflammation in modulating growth and apoptosis in granulosa cells (GCs), the main components of ovarian follicles. ELISA was used to analyze the levels of inflammatory factors (IL-1ß, IL-4, IL-6 and IL-10) in follicular fluid samples and GCs derived from POF patients and healthy normal individuals. CCK-8, flow cytometry and TUNEL assays were used to assess the effect of IL-4 on GC growth and apoptosis. Western blotting was used to examine the effect of IL-4 on the activation of PI3K/Akt, Erk1/2 and Jnk signaling. The results showed that IL-4, IL-1ß and IL-6 levels were increased in follicular fluid samples and GCs derived from POF patients compared with those from healthy individuals. GC growth was weakened when cells were treated with IL-4, while apoptosis was increased. In addition, IL-4 increased the level of p-Akt/Akt in GCs. In addition, LY294002, an inhibitor of PI3K, abolished the effect of IL-4 by inhibiting GC growth and promoting apoptosis. In summary, this study demonstrated that IL-4 levels were increased in POF samples and that IL-4 could inhibit GC growth and induce GC apoptosis by activating PI3K/Akt signaling.