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Adverse nutritional conditions during the perinatal stage are related to early menopause in adulthood; however, the underlying mechanism is still unclear. Herein, we revealed that colostrum-activated ketone body elevation during the postnatal stage regulated primordial follicle reservoir size and then affected ovarian ageing. We found that the expression of the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) was largely enhanced during primordial follicle pool formation after birth and might be activated in the ovaries by colostrum. Reactive oxygen species (ROS) elevation in the ovaries leads to follicle apoptosis to deplete damaged follicles, while Hmgcs2 deficiency enhances follicle apoptosis and thus decreases the size of the primordial follicle pool and leads to premature ovarian ageing (POA), which might be related to the activation of cellular endogenous antioxidant system. All these defects could be rescued by ketone body administration, which suppressed ROS-activated follicle apoptosis. Our results suggest that the internal metabolic homeostasis of newborn mice is critical for the primordial reservoir and that any intrauterine and perinatal undernutrition could result in POA.

In this work, an effective approach based on a nonlinear output frequency response function (NOFRF) and improved convolution neural network is proposed for analog circuit fault diagnosis. First, the NOFRF spectra, rather than the output of the system, are adopted as the fault information of the analog circuit. Furthermore, to further improve the accuracy and efficiency of analog circuit fault diagnosis, the batch normalization layer and the convolutional block attention module (CBAM) are introduced into the convolution neural network (CNN) to propose a CBAM-CNN, which can automatically extract the fault features from NOFRF spectra, to realize the accurate diagnosis of the analog circuit. The fault diagnosis experiments are carried out on the simulated circuit of Sallen–Key. The results demonstrate that the proposed method can not only improve the accuracy of analog circuit fault diagnosis, but also has strong anti-noise ability.

The divergence and continuous evolution of plants and animals contribute to ecological diversity. Promoters and transcription factors (TFs) are key determinants of gene regulation and transcription throughout life. However, the evolutionary trajectories and relationships of promoters and TFs are still poorly understood. Here, we conducted extensive analysis of large-scale multi-omics sequences in 420 animal species and 223 plant species spanning nearly a billion years of evolutionary history. Results showed that promoter GC-content and TF isoelectric points, as features/signatures that accompany long biological evolution, exhibited increasing growth in animal cells but a decreasing trend in plant cells. Furthermore, the evolutionary trajectories of promoter and TF signatures in the animal kingdom provided further evidence that Mammalia as well as Aves evolved directly from the ancestor Reptilia. The strong correlation between promoter and TF signatures indicates that promoters and TFs formed antagonistic coevolution in the animal kingdom, but mutualistic coevolution in the plant kingdom. The distinct coevolutionary patterns potentially drive the plant-animal divergence，divergent evolution and ecological diversity.动物和植物从原始的单细胞生物（绿色鞭毛生物）分化（diverge）并各自持续地演化（evolve），促成了地球上自然生态的多样性（diversity）。在真核生物（eukaryotes）的基因转录（transcription）和调控（regulation）过程中，启动子（promoters）和转录因子（transcription factors）以及它们的相互作用扮演着决定性作用。然而，启动子和转录因子分子的演化轨迹及演化模式目前尚不清楚。通过在跨度大约为十亿年的演化历程上的420个动物物种，223个植物物种基因组和蛋白组序列分析和理化性质分析表明：（1）序列的GC含量（GC-content）和蛋白质的等电点（isoelectric points）可分别作为基因的启动子和转录因子的演化特征印记（signatures）；（2）在动物界，启动子的GC含量和转录因子的等电点，在漫长的演化历程中，表现出同步的持续增长；（3）在植物界，启动子的GC含量和转录因子的等电点，则表现出同步的降低趋势。启动子和转录因子的演化轨迹为“哺乳动物和鸟类一样，都是从爬行动物直接演化而来”提供了新的证据。通过分析启动子和转录因子之间相互作用的理化特征，以及它们之间演化轨迹的强相关性和显著性，表明启动子和转录因子在动物界呈现拮抗的共演化（antagonistic coevolution），而在植物界则呈现互利的共演化（mutualistic coevolution）。该研究为探究启动子与转录因子间的相互作用机理，进一步理解动植物的分化、趋异演化及生态多样性提供了新的洞见。.

SummaryEmbryo implantation requires temporospatial maternal-embryo dialog to regulate the interactions between an activated blastocyst and a receptive endometrium; however, the details of the related cell-specific coordination is largely unknown because of the cellular complexity and dynamic developmental processes of both the embryo and endometrium during peri-implantation. By comparing single-cell RNA (scRNA) data obtained from entire uteri of pregnant and pseudo-pregnant mice with embryos that were in the oviduct (dpc2.5 days post-coitum [dpc]) or had entered the uterus (after 3.5 dpc), we found a maternal estrogen and progesterone signaling-dependent functional differentiation process in which progesterone induced estrogen-responsive luminal epithelial cells to differentiate into two new types of epithelial cells: adhesion epithelial cells (AECs) and supporting epithelial cells (SECs) on 2.5 dpc. In addition to maternal signaling data, the uterine scRNA and corresponding embryo bulk sequencing data were obtained, and analyses revealed that embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, enhancing the attachment of embryos to the endometrium after implantation. Specifically, embryonic signaling induced additional transformation of AECs by preventing adjacent AECs, but not AECs away from the embryo in the implantation chamber, from undergoing apoptosis. Furthermore, we demonstrated that epithelial cell differentiation and related regulatory signaling were largely conserved in humans and mice. In the human endometrium, developmental defects of SOX9-positive epithelial cells similar to luminal epithelial cells were related to thin endometrium. Our work provides comprehensive and systematic information on endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is important for endometrial receptivity and embryo implantation.

Dystocia is a serious problem for pregnant women, and it increases the cesarean section rate. Although uterine dysfunction has an unknown etiology, it is responsible for cesarean delivery and clinical dystocia, resulting in neonatal morbidity and mortality; thus, there is an urgent need for novel therapeutic agents. Previous studies indicated that statins, which inhibit the mevalonate (MVA) pathway of cholesterol synthesis, can reduce the incidence of preterm birth, but the safety of statins for pregnant women has not been thoroughly evaluated. Therefore, to unambiguously examine the function of the MVA pathway in pregnancy and delivery, we employed a genetic approach by using myometrial cell-specific deletion of geranylgeranyl pyrophosphate synthase (Ggps1) mice. We found that Ggps1 deficiency in myometrial cells caused impaired uterine contractions, resulting in disrupted embryonic placing and dystocia. Studies of the underlying mechanism suggested that Ggps1 is required for uterine contractions to ensure successful parturition by regulating RhoA prenylation to activate the RhoA/Rock2/p-MLC pathway. Our work indicates that perturbing the MVA pathway might result in problems during delivery for pregnant females, but modifying protein prenylation with supplementary farnesyl pyrophosphate or geranylgeranyl pyrophosphate might be a strategy to avoid side effects.

Pancreatic ductal cancer (PDAC) has high malignancy and poor prognosis. Long noncoding RNAs (lncRNAs) are associated with high levels of malignancy, including PDAC. However, the biological and clinical significance of negative regulator of antiviral response (NRAV) in PDAC is unclear.To study the regulatory role of lncRNA NRAV in PDAC.GEPIA analyzed lncRNA NRAV and miRNA (miR-299-3p) expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time. The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis, Cell Counting Kit-8 and Transwell analysis. The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics, RNA immunoassay, and fluorescence enzyme analysis.The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients. Functionally, overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells, while knockdown of NRAV reversed these effects. Finally, NRAV was performed as a molecular sponge of miR-299-3p. Moreover, overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.

Gonadal white adipose tissue (gWAT) can regulate gametogenesis via modulation of neuroendocrine signaling. However, the effect of gWAT on the local microenvironment of the gonad was largely unknown. Herein, we ruled out that gWAT had a neuroendocrine effect on gonad function through a unilateral lipectomy strategy, in which cutting off epididymal white adipose tissue could reduce seminiferous tubule thickness and decrease sperm counts only in the adjacent testis and epididymis of the affected gonad. Consistent with the results in males, in females, ovary mass was similarly decreased by lipectomy. We determined that the defects in spermatogenesis were mainly caused by augmented apoptosis and decreased proliferation of germ cells. Transcriptome analysis suggested that lipectomy could disrupt immune privilege and activate immune responses in both the testis and ovary on the side of the lipectomy. In addition, lipidomics analysis in the testis showed that the levels of lipid metabolites such as free carnitine were elevated, whereas the levels of glycerophospholipids such as phosphatidylcholines and phosphatidylethanolamines were decreased, which indicated that the metabolic niche was also altered. Finally, we show that supplementation of phosphatidylcholine and phosphatidylethanolamine could partially rescue the observed phenotype. Collectively, our findings suggest that gWAT is important for gonad function by not only affecting whole-body homeostasis but also via maintaining local metabolic and immune niches.

Polychlorinated biphenyls (PCBs) are a class of persistent organic environmental pollutants with a total of 209 homologs. The homolog 2,3',4,4',5-pentachlorobiphenyl (PCB118) is one of the most important dioxin-like PCBs and is highly toxic. PCB118 can accumulate in human tissues, serum and breast milk, which leads to direct exposure of the fetus during development. In the present study, pregnant mice were exposed to 0, 20 and 100 μg/kg/day of PCB118 during the stage of fetal primordial germ cell migration. Compared with the control group, we found morphological alterations of the seminiferous tubules and a higher sperm deformity rate in the male offspring in the treatment groups. Furthermore, the methylation patterns in the treatment groups of the imprinted genes H19 and Gtl2 in the sperm were altered in the male offspring. We also characterized the disturbance of the expression levels of DNA methyltransferase 1 (Dnmt1), Dnmt3a, Dnmt3b, Dnmt3l, and Uhrf1. The results indicated that intrauterine exposure to low doses of PCB118 could significantly damage the reproductive health of the male offspring. Therefore, attention should be paid to the adverse effects of PCB118 exposure during pregnancy on the reproductive system of male offspring.

The effect of copper on oxidation behavior of a C-Si-Mn steel was investigated. The samples were heated to 820°C and held for 75s under four different dew points with 5vol% hydrogen. The results of glow discharge optical emission spectrometry (GDOES), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) analysis techniques revealed the differences in oxidation. It is proposed that the steel containing 0.3 wt.% copper has less external oxidation of silicon and manganese compared to the steel containing no copper for all different dew points. As researched in this paper the external oxidation of C-Si-Mn steels would be suppressed by adding copper.

Reduction and temperature dually responsive poly(2-(2-methoxyethoxy)ethylmethacrylate-co-oligo(ethylene glycol) methacrylate)-b-poly(e-caprolactone)-SS-poly(e-caprolactone)-b-poly(2-(2-methoxyethoxy)ethylmethacrylat-co-oligo(ethylene glycol) methacrylate) (P(MEO2MA-co-OEGMA)-b-PCL-SS-PCL-b-P(MEO2MA-co-OEGMA)) was synthesized by the combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The copolymer can self-assemble into spherical micelles. After loading doxorubicin (DOX) and photothermal agent Indocyanine green (ICG), the micelles were endowed with synergistic effect of chemotherapy and photothermal therapy to cancer through reduction and temperature dually triggered size-shrinkage and drug release. The micelles showed good reduction and temperature responsiveness due to the presence of disulfide bond and thermoresponsive segments in copolymer. Under reducing conditions, the disulfide bond broke and the micelles were converted into micelles with half the original size, which was conducive to drug release. Near Infrared light (NIR) promoted the photothermal conversion of ICG, so that the micelle underwent a temperature response transition and further promoted the release of drugs. The micelles showed drug release rate, high photothermal conversion efficiency, highly cytotoxic to cancer cells and excellent synergistic photothermal-chemotherapy effect.

Polychlorinated biphenyls (PCBs) are a class of organic pollutants that have been widely found in the environment. The chemical 2,3′,4,4′5-pentachlorobiphenyl (PCB118) is an important dioxin-like PCB compound with strong toxicity. PCB118 can accumulate in adipose tissue, serum and milk in mammals, and it is highly enriched in the follicular fluid. In this study, pregnant mice were exposed to 0, 20 and 100 μg/kg/day of PCB118 during pregnancy at the fetal primordial germ cell migration stage. The methylation patterns of the imprinted genes H19, Snrpn, Peg3 and Igf2r as well as the expression levels of Dnmt1, 3a, 3b and 3l, Uhrf1, Tet2 and Tet3 in fully grown germinal vesicle oocytes were measured in offspring. The rates of in vitro maturation, in vitro fertilization, oocyte spindle and chromosomal abnormalities were also calculated. The results showed that prenatal exposure to PCB118 altered the DNA methylation status of differentially methylated regions in some imprinted genes, and the expression levels of Dnmt1, 3a, and 3l, Uhrf1 and Tet3 were also changed. In addition, PCB118 disturbed the maturation process of progeny mouse oocytes in a dose-dependent manner. Therefore, attention should be paid to the potential impacts of PCB118-contaminated dietary intake during pregnancy on the offspring’s reproductive health.

Objective To observe the clinical efficacy of deep needling at local glossopharyngeum in treatment of dysphagia after stroke. Methods Deep needling at local glossopharyngeum was applied in 85 patients with dysphagia after stroke. Firstly, quick prick was conducted on lingual surface (mainly at the side of paralysis lingualis), Jīnjīn ( EX-HN 12) and Yuye ( EX-HN 13) under the tongue; secondly, filiform needle with the length of 75 mm was used to perform quick prick at posterior wall of pharynx at the affected side about three or four times, and then the needle was removed rapidly. Filiform needle with the length of 75 mm was inserted perpendicularly at Lianquan ( CV 23) towards root of tongue; after deqi, the needle was pushed towards root of tongue in the depth of 60–70 mm, and the needle was retained for 30 min. Meanwhile, the patient was asked to swallow, and the feeling of abnormal deglutition without pain was considered as most appropriate. During needle retention, twirling for reinforcement was applied for two times. The manipulation was conducted once daily, and six days was considered as one course of treatment. Between two courses, one day was free of treatment; and there were four courses in total. Kubota's drinking water test evaluation scale was applied to assess the efficacy after the treatment for two weeks and four weeks. Results The score of Kubota's drinking water test at the early stage of treatment was 5.08 ± 2.28, the score of evaluation of treatment with deep needling at local glossopharyngeum after treatment for two weeks was 4.56 ± 2.32, and the total effective rate was 89.4%; the score of evaluation after treatment for four weeks was 2.80 ± 2.12, and the total effective rate was 95.3%. Compare before the treatment, the score of Kubota's drinking water test was reduced after treatment for two and four weeks (P Conclusion Deep needling at local glossopharyngeum in treatment of dysphagia after stroke has good effect.

Objective To explore the function and mechanism of microRNA-155 to regulate the angiogenesis after the cerebral infarction of rats through the angiotensin II receptor 1 (AT1R)/vascular endothelial growth factor (VEGF) signaling pathway. Methods Female SD rats were chosen for the construction of cerebral infarction model of rats using the modified right middle cerebral artery occlusion. The real-time PCR (RT-PCR) method was employed to detect the expression of microRNA-155 in each group at different time points after the cerebral infarction (1 h, l d, 3 d and 7 d). SD rats were randomly divided into four groups ( n = 20 rats): sham operation group (Sham group), MACO group, MACO+microRNA-155 mimic group, and MACO+microRNA-155 inhibitor group. Sham group was given the free graft, while MACO+microRNA-155 mimic group and MACO+microRNA-155 inhibitor group were treated with microRNA-155 mimic and microRNA-155 inhibitor respectively. The Zea Longa 5-point scale was used to score the neurologic impairment of rats in each group; 2, 3, 5-triphenyl tetrazolium chloride staining to evaluate the volume of cerebral infarction of rats in each group; the immunohistochemistry to detect the expression of CD31; Western blot and RT-PCR to detect the expression of AT1R and VEGF receptor 2 (VEGFR2). Results The expression of microRNA-155 was increased in the cerebral ischemia tissue after the cerebral infarction. It was significantly increased at 1 d of ischemia and maintained at the high level for a long time. Rats in the Sham group had no symptom of neurologic impairment, while rats in the MACO group had the obvious neurologic impairment. After being treated with microRNA-155 inhibitor, the neural function of MACO rats had been improved, with the decreased area of cerebral infarction. But after being treated with microRNA-155 mimic, the neural function was further worsened, with the increased area of cerebral infarction. Results of immunohistochemical assay indicated that microRNA-155 inhibitor could up-regulate the expression of CD31, while microRNA-155 mimic could down-regulate the expression of CD31. The RT-PCR found that, after being treated with microRNA-155 inhibitor, MACO rats had the increased expression of AT1R and VEGFR2 messenger RNA (mRNA); but after being treated with microRNA-155 mimic, the expression of AT1R and VEGFR2 mRNA was decreased. Results of Western blot showed that, after being treated with microRNA-155 inhibitor, MACO rats had the increased expression of AT1R and VEGFR2 mRNA; but after being treated with microRNA-155 mimic, the expression of AT1R and VEGFR2 mRNA was decreased. Conclusions The inhibition of microRNA-155 can improve the neurologic impairment of rats with the cerebral infarction, reduce the volume of cerebral infarction and effectively promote the angiogenesis in the region of ischemia, which may be mediated through AT1R/VEGFR2 pathway.

Zn-Al-Mg alloy coating attracted much attention due to its high corrosion resistance properties, especially high anti-corrosion performance at the cut edge. As the Zn-Al-Mg alloy coating was usually produced by hot-dip galvanizing method, solidification process was considered to influence its microstructure and corrosion properties. In this work, a Zn-Al-Mg cast alloy was melted and cooled to room temperature with different solidification processes, including water quench, air cooling and furnace cooling. Microstructure of the alloy with different solidification processes was characterized by scanning electron microscopy (SEM). Result shows that the microstructure of the Zn-Al-Mg alloy are strongly influenced by solidification process. With increasing solidification rate, more Al is remained in the primary crystal. Electrochemical analysis indicates that with lowering solidification rate, the corrosion current density of the Zn-Al-Mg alloy decreases, which means higher corrosion resistance.