High estrogen during ovarian stimulation induced loss of maternal imprinted methylation that is essential for placental development via overexpression of TET2 in mouse oocytes.

BACKGROUND: Ovarian stimulation (OS) during assisted reproductive technology (ART) appears to be an independent factor influencing the risk of low birth weight (LBW). Previous studies identified the association between LBW and placenta deterioration, potentially resulting from disturbed genomic DNA methylation in oocytes caused by OS. However, the mechanisms by which OS leads to aberrant DNA methylation patterns in oocytes remains unclear. METHODS: Mouse oocytes and mouse parthenogenetic embryonic stem cells (pESCs) were used to investigate the roles of OS in oocyte DNA methylation. Global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels were evaluated using immunofluorescence or colorimetry. Genome-wide DNA methylation was quantified using an Agilent SureSelectXT mouse Methyl-Seq. The DNA methylation status of mesoderm-specific transcript homologue (Mest) promoter region was analyzed using bisulfite sequencing polymerase chain reaction (BSP). The regulatory network between estrogen receptor alpha (ERα, ESR1) and DNA methylation status of Mest promoter region was further detected following the knockdown of ERα or ten-eleven translocation 2 (Tet2). RESULTS: OS resulted in a significant decrease in global 5mC levels and an increase in global 5hmC levels in oocytes. Further investigation revealed that supraphysiological ß-estradiol (E2) during OS induced a notable decrease in DNA 5mC and an increase in 5hmC in both oocytes and pESCs of mice, whereas inhibition of estrogen signaling abolished such induction. Moreover, Tet2 may be a direct transcriptional target gene of ERα, and through the ERα-TET2 axis, supraphysiological E2 resulted in the reduced global levels of DNA 5mC. Furthermore, we identified that MEST, a maternal imprinted gene essential for placental development, lost its imprinted methylation in parthenogenetic placentas originating from OS, and ERα and TET2 combined together to form a protein complex that may promote Mest demethylation. CONCLUSIONS: In this study, a possible mechanism of loss of DNA methylation in oocyte caused by OS was revealed, which may help increase safety and reduce epigenetic abnormalities in ART procedures.

Fetal growth restriction exhibits various mTOR signaling in different regions of mouse placentas with altered lipid metabolism.

Fetal growth restriction (FGR) is a common complication of pregnancy and can have significant impact on obstetric and neonatal outcomes. Increasing evidence has shown that the inhibited mechanistic target of rapamycin (mTOR) signaling in placenta is associated with FGR. However, interpretation of existing research is limited due to inconsistent methodologies and varying understanding of the mechanism by which mTOR activity contributes to FGR. Hereby, we have demonstrated that different anatomic regions of human and mouse placentas exhibited different levels of mTOR activity in normal compared to FGR pregnancies. When using the rapamycin-induced FGR mouse model, we found that placentas of FGR pregnancies exhibited abnormal morphological changes and reduced mTOR activity in the decidual-junctional layer. Using transcriptomics and lipidomics, we revealed that lipid and energy metabolism was significantly disrupted in the placentas of FGR mice. Finally, we demonstrated that maternal physical exercise during gestation in our FGR mouse model was associated with increased fetal and placental weight as well as increased placental mTOR activity and lipid metabolism. Collectively, our data indicate that the inhibited placental mTOR signaling contributes to FGR with altered lipid metabolism in mouse placentas, and maternal exercise could be an effective method to reduce the occurrence of FGR or alleviate the adverse outcomes associated with FGR.

MiR-135a-5p regulates window of implantation by suppressing pinopodes development and decidualization of endometrial stromal cells.

PURPOSE: The window of implantation (WOI) is a brief period during which the endometrium is receptive to embryo implantation. This study investigated the relationship between miR-135a-5p and endometrial receptivity. METHODS: Peripheral blood was collected on the day of ovulation and the 5th day after ovulation for high-throughput sequencing from women who achieved clinical pregnancy through natural cycle frozen embryo transfer. RT-qPCR assessed miR-135a-5p expression in the endometrium tissue or cells during the mouse implantation window or decidualization. Scanning electron microscopy was utilized to observe pinopode morphology and quantity in mice overexpressing miR-135a-5p during the WOI. Human endometrial stromal cells (HESC) and artificial induction of mouse uterine decidualization were used to explore whether miR-135a-5p overexpression inhibits decidualization by regulating HOXA10 and BMPR2. Furthermore, the impact of miR-135a-5p on HESC proliferation and HTR8/SVneo invasion was explored. RESULTS: A total of 54 women were enrolled in the study. bioinformatics analysis and animal models demonstrated that miR-135a-5p was significantly downregulated during the WOI, and its high expression can lead to abnormal pregnancy outcomes. Overexpression of miR-135a-5p resulted in the absence of pinopode in mouse endometrial tissue during the WOI. High miR-135a-5p levels were found to potentially inhibit endometrial tissue decidualization by downregulating HOXA10 and BMPR2 expression. Finally, CEBPD was identified as a potential regulator of miR-135a-5p, which would explain the decreased miR-135a-5p expression during the WOI. CONCLUSION: MiR-135a-5p expression is significantly downregulated during the WOI. High miR-135a-5p levels suppress pinopode development and endometrial tissue decidualization through HOXA10 and BMPR2, contributing to inadequate endometrial receptivity.

Ovarian Stimulation in Mice Resulted in Abnormal Placentation through Its Effects on Proliferation and Cytokine Production of Uterine NK Cells.

Ovarian stimulation is associated with an increased incidence of abnormal placentation. Uterine natural killer (uNK) cells are the major subpopulation of decidual immune cells, which are crucial for placentation. In a previous study, we found that ovarian stimulation impairs uNK cell density on gestation day (GD) 8.5 in mice. However, it was not clear how ovarian stimulation led to a reduction in the density of uNK cells. In this study, we constructed two mouse models, an in vitro mouse embryo transfer model and an estrogen-stimulated mouse model. We used HE and PAS glycogen staining, immunohistochemical techniques, q-PCR, Western blot, and flow cytometry to analyze the mouse decidua and placenta, and the results showed that SO resulted in a fetal weight reduction, abnormal placental morphology, decreased placental vascular density, and abnormal density and function of uNK cells. Our results suggest that ovarian stimulation resulted in aberrant estrogen signaling and may contribute to the disorder of uNK cells caused by ovarian stimulation. Together, these results provide new insights into the mechanisms of aberrant maternal endocrine environments and abnormal placentation.

Association and Interacting Factors between Bronchial Asthma and Attention-deficit Hyperactivity Disorder in Children: Meta-analysis and Systematic Review.

BACKGROUND: This study aims to systematically assess the possible link between bronchial asthma usage and attention-deficit hyperactivity disorder (ADHD) in children. METHODS: PubMed, Web of Science, ScienceDirect, CNKI, Wanfang, and the China Biological Medicine Database (CBM) were searched for relevant articles published from database inception until September 28, 2023. The statistical analyses were conducted using Stata 15.1 software, followed by a quantitative meta-analysis to synthesize the results of the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). RESULTS: A total of 10 articles involving 729,375 participants were included in the meta-analysis. The overall analysis revealed a statistically significant association between ADHD and an increased likelihood of having bronchial asthma, as indicated by a pooled odds ratio (OR) of 1.46 and a 95% confidence interval (CI) ranging from 1.41 to 1.51, p < 0.001, I2 = 58%. Potential associated factors linking bronchial asthma and ADHD in children include demographic characteristics, healthcare access, socioeconomic factors, comorbidities, genetic susceptibility, immune dysregulation, chronic conditions, growth and development factors, and parental/environmental influences. CONCLUSION: This systematic review and meta-analysis presents convincing evidence for a notable link between bronchial asthma and ADHD in children. The results indicate an increased likelihood of bronchial asthma among children with ADHD compared to those without the condition. Additionally, various potential factors can underlie the association between bronchial asthma and ADHD in children, necessitating further research to fully comprehend their complex relationship. These findings have implications for clinical practice, highlighting the need for an integrated approach in managing asthma and ADHD.

Combination of PD-1 inhibitor with GVD (gemcitabine, vinorelbine, liposomal doxorubicin) versus GVD regimen as second-line therapy for relapsed/refractory classical Hodgkin lymphoma.

Patients with classical Hodgkin lymphoma (cHL) who do not achieve complete remission (CR) after second-line chemotherapy have poor clinical outcomes. Besides, conventional salvage chemotherapy regimens have an unsatisfactory CR rate. The present retrospective study reports the efficacy and toxicity of the GVD (gemcitabine, vinorelbine, liposomal doxorubicin) regimen with or without programmed cell death 1 (PD-1) inhibitor for patients with cHL who failed first-line treatment. A total of 103 patients with cHL (GVD+PD-1 group, n = 27; GVD group, n = 76) with response assessment based on positron emission tomography were included. The GVD+PD-1 group tended to have a higher CR rate than GVD group (85·2% vs. 65·8%, P = 0·057) and had a better event-free survival (EFS) (P = 0·034). Subgroup analysis showed that patients with low-risk second-line International Prognostic Score might benefit from the addition of PD-1 inhibitor (GVD+PD-1 vs. GVD, 100·0% vs. 64·7%, P = 0·028) and had better EFS than GVD alone (P = 0·016). Further analysis demonstrated that PD-1 consolidation therapy might provide an EFS benefit (P = 0·007). The toxicity of the GVD+PD-1 regimen was comparable to the GVD regimen, except for higher rates of hypothyroidism and autoimmune pneumonitis, which were manageable. In conclusion, combining a PD-1 inhibitor with a GVD regimen could be a potentially effective second-line therapy for patients with cHL.

Cellular Apoptosis Induced by Deoxynivalenol.

Deoxynivalenol (DON) is synthesized by Fusarium species that frequently infect crops during storage, and it's harm risk to human is reflected in the consumption of infected food crops or indirectly through foods of animal origin. In this study, Hela and Chang liver cells were used to research the cellular apoptosis induced by deoxynivalenol. Cells were treated by DON toxin with a series of concentration and incubated for different time. MTT, fluorescence microscope, flow cytometer and Western blot methods were used to analyze the effect of DON on the cell apoptosis in vitro and in vivo systematically. The results showed that DON was toxic to the cells tested. After being treated by DON, the morphology of Chang livers and Hela cells changed significantly. The DON promoted apoptosis in a dose- and time-dependent manner. The activity of Caspase 3 was significantly increased in DON-induced apoptosis. Moreover, endogenous Glutathione (GSH) level in these cell lines was gradually decreased. In the early apoptosis progress, oxidative stress was induced by DON. When DON reached 10 µg/mL, a markedly increased content of Malondialdehyde (MDA) was detected in both Hela and Chang liver cells. Furthermore, an in vivo test indicated that DON had toxicity to mice by causing weight loss and swollen spleen, and significantly increased expression of AST and ALT. In conclusion, the DON was toxic to mice and could induce the apoptosis of tested cells undergoing a Caspase-3 related pathway.

A prognostic immune risk score for diffuse large B-cell lymphoma.

We constructed a prognostic score for persons with diffuse large B-cell lymphoma (DLBCL) based on infiltrating immune cells. Data of 956 consecutive subjects were retrieved from the Gene Expression Omnibus database and assigned to training (GSE10846, n = 305) or validation (GSE87371 n = 206 and GSE117556 n = 445 combined) cohorts. Proportions of non-lymphoma cells in the sample were inferred using the ESTIMATE algorithm. An immune risk score was constructed comprised of eight types of non-lymphoma immune cells calculated using the CIBERSORT algorithm. Five-year survival of subjects with an immune risk score ≤ 0·45 in the training cohort was better than that of subjects with a score > 0·45 (hazard ratio [HR] = 3·99; 95% confidence interval [CI] = 2·74, 5·82; P < 0·001). HR in the validation cohort was HR = 2·17 (1·47, 3·21; P < 0·001). Enrichment analyses indicated correlations with genes controlling immune-related biological processes and pathways. A nomogram comprised of the immune risk score and most covariates including age, lactate dehydrogenase concentration (LDH), lymphoma-type (germinal centre B cell [GCB] versus non-GCB), Eastern Cooperative Oncology Group performance status (ECOG-PS) and rituximab therapy had a C-statistic of 0·76 compared with C-statistics of 0·69 and 0·69 for the International Prognostic Index (IPI) and Revised International Prognostic Index (R-IPI). These data indicate the immune risk score is an accurate, independent survival predictor in persons with DLBCL.

Ovarian stimulation reduces fetal growth by dysregulating uterine natural killer cells in mice.

Ovarian stimulation is associated with a higher risk of low birth weight. However, the precise mechanisms by which ovarian stimulation increases the chances of low birth weight remain unclear. In this mouse model study, in vivo developed blastocysts that were not exposed to gonadotropins were transferred into pseudopregnant females that had mated naturally (the control group), pseudopregnant females that had been administered a low dose of ovulation-stimulating hormone (the L-SO group) and pseudopregnant females that had been administered a high dose of ovulation-stimulating hormone (the H-SO group). The embryo implantation rate and fetal weight were significantly lower in the L-SO and H-SO groups than in the control group. The density of Dolichos biflorus agglutinin (DBA)+ uterine natural killer (uNK) cells in the decidua basalis was significantly lower in the L-SO and H-SO groups than in the control group. Ovarian stimulation also downregulated a variety of cytokines related to uNK cells that are involved in placental angiogenesis and trophoblast invasion. Collectively, our findings indicate that ovarian stimulation impairs DBA+ uNK cell density in the decidua basalis, which may downregulate uNK-related cytokine secretion and influence placental angiogenesis and restrict fetal growth in mice.

Quaternary Layered Semiconductor Ba2Cr4GeSe10: Synthesis, Crystal Structure, and Thermoelectric Properties.

A quaternary narrow-band-gap semiconductor, Ba2Cr4GeSe10, has been discovered by solid-state reaction. It features a new structure type and crystallizes in the triclinic space group P1̅ (No. 2). The featured 2D anionic layers are constructed by condensed CrSe6 octahedra that are stacking along the c axis, with dispersed GeSe4 tetrahedra and located Ba2+ cations forming these layers. The energy-band structure shows a clear separation between the region of electronic conduction and the zone of electronic insulation. Significantly, an undoped Ba2Cr4GeSe10 sample shows a desirable low thermal conductivity κT (0.51-0.87 W/m·K) and a high Seebeck coefficient S (351-404 µV/K) and reaches a ZT ≈ 0.08 at 773 K.

[Study on effect of Jiangtang decoction on AGEs-RAGE and oxidative stress in KK-Ay mice].

To elucidate the efficacy of Jiangtang decoction(JTD) on AGEs-RAGE and oxidative stress in type 2 diabetic model KK-Ay mice. Fifty KK-Ay mice were randomly divided into 5 groups as follows： model group, metformin group, low-dose, medium-dose and high-dose of JTD group, with 10 C57BL/6J as normal group. All groups are orally administrated with equal distilled water, 250 mg•kg⁻¹ metformin hydrochloride, 2, 4,8 g•kg⁻¹ JTD, equal distilled water respectively, once per day for 12 weeks. Alanine aminotransferase(ALT), creatinine(CREA), urea nitrogen(BUN),advanced glycation end products(AGEs) and receptor of glycation end products(RAGE) in blood or urine were measured during the experiments. Furthermore, on the day of the sacrifice, kidney was collected, and electronic microscopy and immunohistochemistry were performed to evaluate the protective renal effect of JTD. In addition, the levels of AGEs, RAGE, Cata-lase(CAT) and superoxide dismutase(SOD) were assessed by Western blot, Real-time PCR or ELISA to analyze the efficacy of JTD. This study demonstrated that JTD might protect kidney of KK-Ay by down-regulating the expression of AGEs, RAGE and oxidative stress.

Concerted Rattling in CsAg5 Te3 Leading to Ultralow Thermal Conductivity and High Thermoelectric Performance.

Thermoelectric (TE) materials convert heat energy directly into electricity, and introducing new materials with high conversion efficiency is a great challenge because of the rare combination of interdependent electrical and thermal transport properties required to be present in a single material. The TE efficiency is defined by the figure of merit ZT=(S(2) σ) T/κ, where S is the Seebeck coefficient, σ is the electrical conductivity, κ is the total thermal conductivity, and T is the absolute temperature. A new p-type thermoelectric material, CsAg5 Te3 , is presented that exhibits ultralow lattice thermal conductivity (ca. 0.18 Wm(-1) K(-1) ) and a high figure of merit of about 1.5 at 727 K. The lattice thermal conductivity is the lowest among state-of-the-art thermoelectrics; it is attributed to a previously unrecognized phonon scattering mechanism that involves the concerted rattling of a group of Ag ions that strongly raises the Grüneisen parameters of the material.

Supercubooctahedron (Cs6Cl)2Cs5[Ga15Ge9Se48] Exhibiting Both Cation and Anion Exchange.

A novel type of supertetrahedral connectivity is exhibited by the 72-atom discrete supercubooctahedron in (Cs6Cl)2Cs5[Ga15Ge9Se48] (1), which undergoes both cation and anion exchange, as revealed by unambiguous single-crystal X-ray diffraction data. Electronic-structure studies helped to understand the Ge/Ga distribution.

Superionic adjustment leading to weakly temperature-dependent ZT values in bulk thermoelectrics.

Thermoelectric (TE) materials are of worldwide interest for energy sustainability through direct waste-heat-to-electricity conversion. Practically, a TE power generator requires a large working temperature gradient; to achieve high efficiency, key TE materials with high ZT values are necessary and, furthermore, their ZT values should decline as little as possible over the imposed temperature range. Unfortunately, sharp ZT declines in all of the known materials are inevitable. Here we found the bulk superionic α-Ag(1-x)CuSe material exhibits unusual weakly temperature-dependent ZT values in the range of 480-693 K with the smallest ZT-T slope known to date. These result from the Seebeck coefficient balance of the countercontributions of holes and electrons and the weakly temperature-dependent thermal conductivity.

Syntheses, Characterization, and Optical Properties of Centrosymmetric Ba3(BS3)1.5(MS3)0.5 and Noncentrosymmetric Ba3(BQ3)(SbQ3).

The most advanced UV-vis and IR NLO materials are usually borates and chalcogenides, respectively. But thioborates, especially thio-borometalates, are extremely rare. Here, four new such compounds are discovered by solid state reactions representing 0D structures constructed by isolated BQ3 trigonal planes and discrete MQ3 pyramids with Ba(2+) cations filling among them, centrosymmetric monoclinic P21/c Ba3(BS3)1.5(MS3)0.5 (M = Sb, Bi) 1, 2 with a = 12.9255(9), 12.946(2) Å; b = 21.139(2), 21.170(2)Å; c = 8.4194(6), 8.4207(8) Å; ß = 101.739(5), 101.688(7)°; V = 2252.3(3), 2259.9(3) Å(3) and noncentrosymmetric hexagonal P6̅2m Ba3(BQ3)(SbQ3) (Q = S, Se) 3, 4 with a = b = 17.0560(9), 17.720(4) Å; c = 10.9040(9), 11.251(3) Å; V = 2747.1(3), 3060(2) Å(3). 3 exhibits the strongest SHG among thioborates that is about three times that of the benchmark AgGaS2 at 2.05 µm. 1 and 3 also show an interesting structure relationship correlated to the size mismatching of the anionic building units that can be controlled by the experimental loading ratio of B:Sb. Syntheses, structure characterizations, and electronic structures based on the density functional theory calculations are reported.

[Relationship between autophagy and T2DM and intervention effect of traditional Chinese medicine].

Insulin resistance and insulin secretion deficiency are main machanisms in inducing type 2 diabetes mellitus (T2DM), and mitochondria damage plays an important role in them. Research shows that autophagy is a self-protective mechanism of cells, which plays an important role in maintaining the normal structure and function of pancreatic ß cells and improving insulin resistance. Previous studies show that traditional Chinese medicine can regulate cell autophagy to influence ß cells and insulin resistance, type 2 diabetes mellitus and its complications. Thus this review will talk about the process of the relationship between autophagy and T2DM and the intervention effect of traditional Chinese medicine.

Chemical modification and energetically favorable atomic disorder of a layered thermoelectric material TmCuTe2 leading to high performance.

Thermoelectric (TE) materials have continuously attracted interest worldwide owing to their capability of converting heat into electricity. However, discovery and design of new TE material system remains one of the greatest difficulties. A TE material, TmCuTe2 , has been designed by a substructure approach and successfully synthesized. The structure mainly features CuTe4 -based layers stacking along the c axis that are separated by Tm(3+) cations. Such an intrinsic Cu site vacancy structure undergoes a first-order phase transition at around 606 K driven by the energetically favorable uniform Cu atom re-distribution on the covalent CuTe4 -based layer substructure, as shown by crystal structure simulations and variable-temperature XRD data. Featured with very low thermal conductivity (ca. 0.6 W m(-1) K(-1) ), large Seebeck coefficient (+185 µV K(-1) ), and moderate electrical conductivity (220 S cm(-1) ), TmCuTe2 has a maximum ZT of 0.81 at 745 K, which is nine times higher than the value of 0.09 for binary Cu2 Te, thus making it a promising candidate for mid-temperature TE applications. Theoretical studies uncover the electronic structure modifications from the metallic Cu2 Te to the narrow gap semiconductor TmCuTe2 that lead to such a remarkable performance enhancement.

Electron-deficient telluride Cs3Cu20Te13 with sodalite-type network: syntheses, structures, and physical properties.

The first sodalite-type telluride, Cs3Cu20Te13, has been successfully synthesized by solid-state reactions. The single-crystal X-ray diffraction data reveal its cubic symmetry and lattice parameters of a = 14.7557(6) Å, V = 3212.8(2) Å(3), and Z = 4. The three-dimensional network is constructed by (CuTe)12 tetrakaidecahedra centered by different guest species (either a Cs(+) or a Te(2-)@Cu8 cube) extending in a 2 × 2 × 2 supercell with respect to the conventional sodalite. Density functional theory analysis uncovers the unique feature of the p-type metallic sodalite framework accommodating anionic guest species, which agrees well with the experimental metallic electrical conductivity and Pauli paramagnetism.

Ethyl pyruvate alleviates NLRP3/Caspase-1/GSDMD-mediated neuronal pyroptosis in neonatal rats with hypoxic-ischemic brain damage.

Pyroptosis is an inflammation-associated programmed cell death, and neuroinflammation is strongly associated with severe neurological deficits in neonatal hypoxic-ischemic encephalopathy (HIE). Ethyl pyruvate (EP), a known anti-inflammatory agent, has shown promise in the treatment of hypoxic-ischemic brain damage (HIBD) rats; nevertheless, the therapeutic mechanism of EP and its capacity to suppress neuronal pyroptosis in HIBD rats remain unclear. In both the neonatal Rice-Vannucci rat model and the OGD/R model, this study examined alterations in the NLRP3/Caspase-1/GSDMD classical pyroptosis pathway in hippocampal neurons during HIE and the potential inhibitory impact of ethyl pyruvate on this pathway. We used HE staining, immunofluorescence double staining, transmission electron microscopy, and western blot to demonstrate that EP effectively inhibited hippocampal neuronal pyroptosis and attenuated the activation of the NLRP3/Caspase-1/GSDMD signaling pathway in HIBD rats, which resulted in a reduction of neuroinflammation and facilitated neural recovery. The results suggest that EP may be a promising neuroprotective agent for treating HIE.

Concentration effects on the local structures and electronic properties of ErxBaY2-xF8: a first-principles study.

Er3+doped barium yttrium fluoride (BaY2F8) crystal has gained long-term attention due to its great potential in laser and medical device applications. However, the local structures of Er3+doped BaY2F8system (Er:BYF) remain uncertain, and the effect of doping concentration on structures and properties is unknown. Therefore, in this study, the first-principles study of the structural evolution of ErxBaY2-xF8(x= 0.125, 0.25) crystals was carried out. By means of density functional theory and particle swarm optimization algorithm, the stable structures of Er:BYF crystals with two different concentrations are shown as standard monoclinic structures withP2 symmetry for the first time. The impurity Er3+ions successfully enter the main lattice, replacing the Y3+ions, and forming a [ErF8]5-polyhedron withC2point group symmetry. By calculating the electronic properties, the band gap values of the two structures are significantly reduced compared with that of pure BaY2F8crystal. However, the conduction band does not break through the Fermi level, and the crystals still maintain the insulation characteristic. According to the calculation of the electron local density function, we conclude that Er-F and Y-F in Er:BYF are connected by ionic bonds. These results fill a theoretical gap in the study of Er:BYF crystals and provide inspiration for structural evolution and material design at different doping concentrations.