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The mechanical parameters of Cerasus humilis are the basic data for subsequent studies on fruit deformation, damage, and movement characteristics during harvesting and transportation, but these parameters are rarely reported. Relevant mechanical parameters of whole fruit compression are calculated by comparing physical tests and virtual simulations. The orthogonal rotating combined experimental design was used to arrange the simulation tests, with the elastic modulus (E), yield limit (Ey), and tangent modulus (Et) as the influence factors and compression force as the result. Response surface optimization was employed to find the closest test point to the force–deformation curve of the physical test. The parameters of the pulp test point are as follows: E = 0.923 MPa, Ey = 0.0897 MPa, and Et = 0.478 MPa. Results show that the step on the force–deformation curve was not the beginning of the pulp yield, which was substantially earlier than the strain rate at the simulation step. The region of increased stress in the pulp first appeared at the junction with the core due to stress concentration. Combining virtual and physical tests to solve the mechanical parameters of fruits is more suitable than testing the standard pulp sample.

A sunken solar greenhouse is the original type of greenhouse in China, its soil wall thermal storage performance is better and low cost. Higher benefits of stereoscopic planting in sunken solar greenhouses, while repeated use of the substrate can produce pathogens, so high-temperature smothering is used for sterilization in the summer months of June to August. To investigate the mechanism of indoor temperature and humidity variation and fungicidal effect in a sunken solar greenhouse, a single cross-sectional test of temperature and humidity in sunken solar greenhouse during the smothering period was conducted using wireless sensors. The results showed that: The maximum value of indoor temperature at noon was 69.5°C the temperature value of all measurement points was greater than 50°C for 3h, when removing the measurement points at the upper surface of the ground, the relative humidity value of other measurement points was less than 60% for 5h. During the daytime period, when the indoor temperature is greater than 28°C in the interval 7:00-12:00, the initial relative humidity value of each measurement point is located at 70%-85%; when the weighted temperature of each measurement point starts to rise at a rate of 1.1°C/10min, the weighted humidity of each measurement point declining is 1.3%/10min; the determination of the rate of change of indoor temperature and humidity during the daytime and the starting value can provide a basis for indoor plants to take measures to sterilize at high temperature.

In view of the problem of plant entanglement threshing roller in the process of mechanized flax harvesting, a comb-brush air-suction composite flax capsule harvesting test stand was designed based on the harvesting method of harvesting capsules independently and then breaking the capsules to thresh them. The following four parameters were selected as experimental factors: the shape of comb tooth cross-section, the rotational speed of comb roller, the relative speed of machine travel and the air volume of centrifugal fan. The following four indicators were chosen as the experimental indicators: capsule removal rate, capsule breakage rate, capsule collection rate and plant winding rate. A four-factor and three-level orthogonal test was conducted. The results showed that the optimal combination of test factors was as follows: the shape of comb tooth cross-section was rectangular, the rotational speed of the brush roller was 90 rad/min, the speed of machine travel relative to the plant was 80 mm/s and the air volume of centrifugal fan was 6000 m3/h. Under the condition of better experiment parameters combination, the capsule removal rate was 96.45%, capsule shell breaking rate was 98.79%, capsule collection rate was 95.65% and flax plants winding rate was 2.52%. The comb-brush air-suction composite flax capsule harvesting test bench provided the feasibility scheme for the problem of plant winding thresher roller and capsule collection.

Background The biological effects of cerium dioxide nanoparticles (CeO2NPs), a novel material in the biomedical field, have attracted widespread attention. Our previous study confirmed that exposure to CeO2NPs during pregnancy led to abnormal trophoblast invasion during early placental development, thereby impairing placental development. The potential mechanisms may be related to low-quality decidualization triggered by CeO2NPs exposure, such as an imbalance in trophoblast invasion regulators secreted by decidual cells. However, the intermediate link mediating the “dialogue” between decidual cells and trophoblasts during this process remains unclear. As an important connection between cells, exosomes participate in the “dialogue” between endometrial cells and trophoblasts. Exosomes transfer bioactive microRNA into target cells, which can target and regulate the level of mRNA in target cells. Results Here, we constructed a mice primary uterine stromal cell-induced decidualization model in vitro, and detected the effect of CeO2NPs exposure on the expression of decidual-derived exosomal miRNAs by high-throughput sequencing. Bioinformatics analysis and dual-luciferase reporter assays were performed to identify target genes of the screened key miRNAs in regulating trophoblast invasion. Finally, the role of the screened miRNAs and their target genes in regulating trophoblast (HTR-8/SVneo cells) invasion was confirmed. The results showed that CeO2NPs exposure inhibited trophoblast invasion by promoting miR-99a-5p expression in decidual-derived exosomes, and Ppp2r5a is a potential target gene for miR-99a-5p to inhibit trophoblast invasion. Conclusions This study revealed the molecular mechanism by which CeO2NPs exposure inhibits trophoblast invasion from the perspective of decidual derived exosomal miRNAs. These results will provide an experimental basis for screening potential therapeutic targets for the negative biological effects of CeO2NPs exposure and new ideas for studying the mechanism of damage to trophoblast cells at the decidual-foetal interface by harmful environmental or occupational factors.

Background Trauma in the elderly is gradually growing more prevalent as the aging population increases over time. The purpose of this study is to assess hospitalization costs of the elderly trauma population and analyze the association between those costs and the features of the elderly trauma population. Methods In a retrospective analysis, data on trauma patients over 65 who were admitted to the hospital for the first time due to trauma between January 2017 and March 2022 was collected from a tertiary comprehensive hospital in Baotou. We calculated and analyzed the hospitalization cost components. According to various therapeutic approaches, trauma patients were divided into two subgroups: non-surgical patients (1320 cases) and surgical patients (387 cases). Quantile regression was used to evaluate the relationship between trauma patients and hospitalization costs. Results This study comprised 1707 trauma patients in total. Mean total hospitalization costs per patient were ¥20,741. Patients with transportation accidents incurred the highest expenditures among those with external causes of trauma, with a mean hospitalization cost of ¥24,918, followed by patients with falls at ¥19,809 on average. Hospitalization costs were dominated by medicine costs (¥7,182 per capita). According to the quantile regression results, all trauma patients' hospitalization costs were considerably increased by length of stay, surgery, the injury severity score (16–24), multimorbidity, thorax injury, and blood transfusion. For non-surgical patients, length of stay, multimorbidity, and the injury severity score (16–24) were all substantially linked to higher hospitalization costs. For surgical patients, length of stay, injury severity score (16–24), and hip and thigh injuries were significantly associated with greater hospitalization costs. Conclusions Using quantile regression to identify factors associated with hospitalization costs could be helpful for addressing the burden of injury in the elderly population. Policymakers may find these findings to be insightful in lowering hospitalization costs related to injury in the elderly population.

Background: Cumulative studies supported that HER2 low is a biological subtype of breast cancer however controversial conclusions were made in different real-world studies. We explored the differences in clinical characteristics and short-term and long-term prognosis outcomes between HER2 0 and HER2 low early breast cancer patients using an ambidirectional cohort in China. Methods: Among 711 patients who first diagnosed with breast cancer between January 1, 2016 to December 31, 2020, those with neoadjuvant chemotherapy were screened. Finally, 303 patients were included in our analysis and 90 patients (29.7%) with HER2 = 0 and 213 patients (70.3%) with HER2 = 1+. Propensity score method with inverse probability of treatment weighting was applied to account for the confounders. Results from weighted Kaplan-Meier curve and log-rank test, weighted logistic and cox regression were used to compare two groups. Results: Regarding the baseline and clinical characteristics between HER2-low and HER2-0 group. Family history of caner, ER, PR, HR, Ki-67 labeling index and treatment regimens were observed different. 35% patients used EC-T/EC-P/AC-P treatment. Regarding the bpCR, ORR and rwOS, after multivariate adjustment and propensity score method, no evidence indicated any differences between two groups. Conclusions: HER2-low as a specific biological subtype remains difficult. The HER2-low expression can differ from the therapeutic value in neoadjuvant setting among early breast cancer patients. Further research on the understanding of HER2 low breast cancer is necessary.

Numerous studies have suggested the possibility of explaining the etiology of metabolic syndrome through DNA methylation. DNA methyltransferase 3B (DNMT3B) plays an important role in de novo DNA methylation. There was an alteration in maternal (F0) endometrial function, which might lead to growth and developmental disorder in offspring (F1). In this study, we investigated the effect of maternal endometrial DNMT3B deficiency on the metabolism in offspring. We constructed endometrial DNMT3B conditional knockout female mice (cKO) which were mated with normal C57BL/6 male mice to obtain the F1 generation. Further, to study the development of these offspring, we observed them at three different life stages which included the 6-week-old juvenile, 9-week-old sub-adult and 12-week-old adult. Follow the detection of a range of metabolism-related indicators, we found that in the cKO F1 generation, liver triglyceride level was significantly elevated in 9-week-old female mice, lipid droplet deposition was significantly increased in 9-week-old and 12-week-old mice, and the expression of lipid metabolism key factors in the liver was markedly decreased except of 6-week-old male mice. These results indicate that maternal endometrial DNMT3B conditional knockout leads to imbalance in hepatic metabolism in F1 generation, the mechanism of which requires further discussion.

A series of ZSM-5@MCM-41 core–shell composite materials prepared via a multi-cycle-sol–gel coating strategy is investigated as the catalyst for benzene alkylation with ethylene, in which both ethylbenzene and para-diethylbenzene (p-DEB) are aimed as the target products. With multi-cycle-sol–gel coating, the external acid sites on the samples are gradually passivated by the inert MCM-41 shell. As a result, the shape selectivity to p-DEB is greatly enhanced. Nevertheless, the coating of mesoporous MCM-41 shell on ZSM-5 accelerates deactivation of the catalyst only due to the dilution effect of ZSM-5 content in the catalyst at the same space velocity, which is a reason that core–shell ZSM-5@MCM-41 will potentially be a practical catalyst in shape selective alkylation of benzene. In order to enhance the yield of p-DEB on ZSM-5@MCM-41, the reaction conditions at the fixed bed reactor including temperature, the molar rate of benzene to ethylene and GHSV, are also optimized.

Numerous studies have suggested the possibility of explaining the etiology of metabolic syndrome through DNA methylation. DNA methyltransferase 3B (DNMT3B) plays an important role in

Sufficient decidualization is necessary to maintain successful pregnancy. The physiological function and underlying molecular mechanisms of intergenic long non-coding RNA (lincRNAs) in this process remain largely unknown. Herein, we identified a lincRNA, RP24-315D19.10, which is highly expressed during mouse decidualization during early pregnancy, by performing RNA-sequencing (RNA-seq) analysis and weighted gene co-expression network analysis (WGCNA). Detailed cell and molecular assays revealed that lincRNA RP24-315D19.10 knockdown blocked decidualization in primary mouse endometrial stromal cells (mESCs), suggesting that RP24-315D19.10 is a promoting factor for decidualization. Mechanistically, cytoplasmic RP24-315D19.10 directly interacted with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and upregulated its protein level. Moreover, we found that hnRNPA2B1 is involved in the regulation of decidualization through loss- and gain-of-function studiesin vitro. Clinically, patients diagnosed with spontaneous miscarriage were found to have lower hnRNPA2B1 levels than healthy individuals, suggesting that RP24-315D19.10-regulated hnRNPA2B1 may participate in the development and progression of early spontaneous abortion. Our study indicates that RP24-315D19.10 enhances endometrial decidualization in a hnRNPA2B1-dependent manner, providing further insights into this physiological process.

The relationship between the oral microbiota and type 1 diabetes (T1D) remains unclear. We aimed to evaluate the variations in the oral microbiome in T1D and identify potentially associated bacterial factors.We performed high-throughput sequencing of the V3-V4 area of theCompared to the CON group, the NT1D group was characterized by decreased diversity and increased abundance of genera harboring opportunistic pathogens, while this trend was partially reversed in the CT1D group. Differential genera between groups could distinguish the NT1D group from the CON group (AUC = 0.933) and CT1D group (AUC = 0.846), respectively. Moreover, T1D-enriched genera were closely correlated with HbA1c, FBG and WBCs levels.Our results showed that the acute phase of T1D was characterized by oral microbiota dysbiosis, which could be partially ameliorated via glycemic control. The possible role of oral microbiota dysbiosis on oral health and systemic metabolic status in T1D warrants further mechanistic investigation.

Cationic polymeric materials and cell-penetrating peptides (CPPs) were often used as the delivery vectors in the evaluation of nucleic acid therapeutics. 10-23 DNAzyme is a kind of potential antisense therapeutics by catalytic cleavage of the disease-related RNAs. Here, lipofectamine 2000 and Tat peptide were evaluated for their effect on the catalytic activity of 10-23 DNAzyme, with the observed rate constant, thermal stability, CD spectra, and PAGE analysis, with a duplex DNA mimicking DNAzyme-substrate as a control. It was shown that the cationic carriers had a negative effect on the catalytic performance of the 10-23 DNAzyme. Significantly, the destabilizing effect of the cationic carriers on the duplex formation was noteworthy, as a duplex formation is an essential prerequisite in the silencing mechanisms of antisense and RNAi.

Existing evidence suggests that adverse pregnancy outcomes are closely related to dietary factors. Folate plays an important role in neural tube formation and fetal growth, folate deficiency is a major risk factor of birth defects. Our early studies showed that folate deficiency could impair enddecidualization, however, the mechanism is still unclear. Dysfunctional autophagy is associated with many diseases. Here, we aimed to evaluate the adverse effect of folate deficiency on endometrial decidualization, with a particular focus on endometrial cell autophagy. Mice were fed with no folate diet in vivo and the mouse endometrial stromal cell was cultured in a folate-free medium in vitro. The decrease of the number of endometrial autophagosomes and the protein expressions of autophagy in the folate-deficient group indicated that autophagosome formation, autophagosome-lysosome fusion, and lysosomal degradation were inhibited. Autophagic flux examination using mCherry-GFP-LC3 transfection showed that the fusion of autophagosomes with lysosomes was inhibited by folate deficiency. Autophagy inducer rapamycin could reverse the impairment of folate deficiency on endometrial decidualization. Moreover, folate deficiency could reduce autophagy by disrupting AMPK/mTOR signaling, resulting in aberrant endometrial decidualization and adverse pregnancy outcomes. Further co-immunoprecipitation examination showed that decidual marker protein Hoxa10 could interact with autophagic marker protein Cathepsin L, and the interaction was notably reduced by folate deficiency. In conclusion, AMPK/mTOR downregulated autophagy was essential for aberrant endometrial decidualization in early pregnant mice, which could result in adverse pregnancy outcomes. This provided some new clues for understanding the causal mechanisms of birth defects induced by folate deficiency.

In order to realize the rapid and non-destructive detection of fresh Cerasus Humilis’ (CH) classification, and promote the deep-processing of post-harvest fresh fruit and improve market competitiveness, this study proposed a nonlinear identification method based on genetic algorithm (GA) optimized back propagation (BP) neural network of different varieties of fresh CH fruit. “Nongda-4”, “Nongda-5”, and “Nongda-7” fresh CH fruit were selected as research objects to collect their visible/near-infrared spectral data dynamically. The original spectra were preprocessed by moving smoothing (MS) and standard normal variate (SNV) methods, for the characteristic wavelengths were extracted with four dimension-reducing methods, namely principal components analysis (PCA), competitive adaptive reweighed sampling (CARS), CARS-mean impact value (CARS-MIV), and random frog (RF) algorithm. Finally, the BP prediction models were established based on full-spectrum and characteristic wavelengths. At the same time, the GA optimization was used to optimize the initial weight and threshold of the BP neural network and compared with the partial least squares’ discrimination analysis (PLS-DA) linear model. Through comparing the MS (7)+SNV was proved to be the best preprocessing method, the CARS-MIV-GA-BP model had the best discriminant accuracy, the prediction set accuracy was 98.76%, of which the variety “Nongda-4” and “Nongda-5” recognition rate were 100%, the variety “Nongda-7” recognition rate was 96.29%. The results show that the GA can effectively optimize the initial weights and threshold randomization of the BP neural network, improve the discrimination accuracy of CH varieties, and the CARS-MIV algorithm can effectively reduce the number of input nodes of the BP neural network model, simplify the structure of BP neural network. This study provides a new theoretical basis for the detection of fresh CH fruit classification.

Sparganosis, caused by the plerocercoid larvae of

To assist physicians in the diagnosis and treatment planning of tumor, a robust and automatic liver and tumor segmentation method is highly demanded in the clinical practice. Recently, numerous researchers have improved the segmentation accuracy of liver and tumor by introducing multiscale contextual information and attention mechanism. However, this tends to introduce more training parameters and suffer from a heavier computational burden. In addition, the tumor has various sizes, shapes, locations, and numbers, which is the main reason for the poor accuracy of automatic segmentation. Although current loss functions can improve the learning ability of the model for hard samples to a certain extent, these loss functions are difficult to optimize the segmentation effect of small tumor regions when the large tumor regions in the sample are in the majority.We propose a Liver and Tumor Segmentation Network (LiTS-Net) framework. First, the Shift-Channel Attention Module (S-CAM) is designed to model the feature interdependencies in adjacent channels and does not require additional training parameters. Second, the Weighted-Region (WR) loss function is proposed to emphasize the weight of small tumors in dense tumor regions and reduce the weight of easily segmented samples. Moreover, the Multiple 3D Inception Encoder Units (MEU) is adopted to capture the multiscale contextual information for better segmentation of liver and tumor.Efficacy of the LiTS-Net is demonstrated through the public dataset of MICCAI 2017 Liver Tumor Segmentation (LiTS) challenge, with Dice per case of 96.9We demonstrated the effectiveness of LiTS-Net and its core components for liver and tumor segmentation. The S-CAM is designed to model the feature interdependencies in the adjacent channels, which is characterized by no need to add additional training parameters. Meanwhile, we conduct an in-depth study of the feature shift proportion of adjacent channels to determine the optimal shift proportion. In addition, the WR loss function can implicitly learn the weights among regions without the need to manually specify the weights. In dense tumor segmentation tasks, WR aims to enhance the weights of small tumor regions and alleviate the problem that small tumor segmentation is difficult to optimize further when large tumor regions occupy the majority. Last but not least, our proposed method outperforms other state-of-the-art methods on both the LiTS dataset and the 3Dircadb dataset.

Piston action describes the phenomenon that air at the train nose is pushed forward by the increased pressure and air at the train rear is drawn forward by the decreased pressure when a train passes through a tunnel. The variation of pressure changes the thermal environment inside the tunnel and promotes the frost damage generation in cold season. In this paper, a fluid-thermal-solid involving piston action is proposed. A high-speed railway tunnel that is located in the northeast of China is set in the background, and the influence of outside air temperature and train velocity on the thermal environment inside the tunnel are simulated and analyzed. The piston action can significantly change the temperature inside the tunnel, especially at the ends of tunnel. The temperature distribution is characterized by three zones, including disturbed zones at two sides of tunnel and undisturbed zone at tunnel middle. The freezing length is closely related to air temperature and train velocity. And also, the lengths are different at vault and rail of tunnel portal, which indicates that the anti-freezing measure should be different at these positions considering the cost. This paper can help us understand the temperature evolution process of tunnels under the action of piston wind and provide some guidelines for structural design of cold regional tunnels.

A comb-type harvesting test bench was designed to address low fruit collection rate and theoretical analysis and simulation analysis of the harvesting process were carried out in this work. Single factor simulation experiment and bench experiment were carried out, and fruit collection rate was used as the evaluation index. The motor speed, bending angle of comb teeth and radial diameter of comb teeth arrangement were selected as the experimental factors. Results showed that the collection rate decreased with the increase of motor speed; and increased with the increase of the bending angle of comb teeth or the radial diameter of comb teeth arrangement. The orthogonal experiment of three-factor and three-level quadratic rotation centre combination was performed. The results showed that motor speed had the largest effect on collection rate, followed by radial diameter of comb teeth arrangement and bending angle of comb teeth. The optimal parameter combination was predicted by the response surface model as follows: motor speed of 25 r/min, bending angle of comb teeth of 120°, radial diameter of comb teeth arrangement of 868.45 mm and correspondingly the collection rate reached 91.51%. Based on actual harvesting efficiency and the machining problems of the test bench, the bench experiment was performed with the motor speed of 25 r/min, the bending angle of comb teeth of 120°, the radial diameter of comb teeth arrangement of 900 mm, and the collection rate was 93.82%. The relative error with the predicted optimal result was 2.48%, achieving the purpose of improving the collection rate.

Decidualization of endometrial stromal cells (ESCs) accompanied with embryo implantation is a key process in mammalian reproduction. Evidence suggests that maintenance of decidual cells function is essential. As a critical part in post-transcriptional gene regulation, microRNAs (miRNAs/miR) have been confirmed to be involved in decidualization. However, whether microRNAs regulate decidual cells function has not been reported. Aiming to clarify the role and potential mechanism of miRNAs in decidual cells, artificial induced decidualization model in mice was established. There are 94 differentially expressed miRNAs (≥two-fold change) between decidualized and non-decidualized tissues, including 60 upregulated and 34 downregulated miRNAs. Of the differentially expressed miRNAs, mmu-miR-21a is up-regulated. RT-qPCR also confirmed the up-regulation of mmu-miR-21a following decidualization in vivo and in vitro, and bioinformatic analysis and luciferase activity assay revealed Pdcd4 to be the target gene of mmu-miR-21a. Inhibition of mmu-miR-21a restrained secretory function of decidual cells induced by mESCs, accompanied with increase of Pdcd4 expression and resulted in the increase of cell apoptosis. In addition, we also determined the expression of hsa-miR-21 and Pdcd4 in human proliferative endometrial tissues and decidua tissues. hsa-miR-21 showed higher expression in human decidua tissues compared with proliferative endometrial tissues, while expression of Pdcd4 was contrary to that of hsa-miR-21. Similarly, cell apoptosis increased significantly in human endometrial stromal cell line in response to inhibition of hsa-miR-21. Collectively, we conclude that mmu-miR-21a/hsa-miR-21 may play a key role in regulating the function of decidual cells by inhibiting cell apoptosis through targeting Pdcd4.

OBJECTIVE: To investigate efficiency of radiomics signature to preoperatively predict histological features of aggressive extrathyroidal extension (ETE) in papillary thyroid carcinoma (PTC) with biparametric magnetic resonance imaging findings. MATERIALS AND METHODS: Sixty PTC patients with preoperative MR including T2WI and T2WI-fat-suppression (T2WI-FS) were retrospectively analyzed. Among them, 35 had ETE and 25 did not. Pre-contrast T2WI and T2WI-FS images depicting the largest section of tumor were selected. Tumor regions were manually segmented using ITK-SNAP software and 107 radiomics features were computed from the segmented regions using the open Pyradiomics package. Then, a random forest model was built to do classification in which the datasets were partitioned randomly 10 times to do training and testing with ratio of 1:1. Furthermore, forward greedy feature selection based on feature importance was adopted to reduce model overfitting. Classification accuracy was estimated on the test set using area under ROC curve (AUC). RESULTS: The model using T2WI-FS image features yields much higher performance than the model using T2WI features (AUC = 0.906 vs. 0.760 using 107 features). Among the top 10 important features of T2WI and T2WI-FS, there are 5 common features. After feature selection, the models trained using top 2 features of T2WI and the top 6 features of T2WI-FS achieve AUC 0.845 and 0.928, respectively. Combining features computed from T2WI and T2WI-FS, model performance decreases slightly (AUC = 0.882 based on all features and AUC = 0.913 based on top features after feature selection). Adjusting hyper parameters of the random forest model have negligible influence on the model performance with mean AUC = 0.907 for T2WI-FS images. CONCLUSIONS: Radiomics features based on pre-contrast T2WI and T2WI-FS is helpful to predict aggressive ETE in PTC. Particularly, the model trained using the optimally selected T2WI-FS image features yields the best classification performance. The most important features relate to lesion size and the texture heterogeneity of the tumor region.

Effective intracerebral delivery acetylcholinesterase (AChE) reactivator is key for the acute organophosphorus (OPs) poison treatment. However, the blood-brain barrier (BBB) restricts the transport of these drugs from blood into the brain. Herein, we developed transferrin receptor (TfR) aptamer-functionalized liposomes (Apt-LP) that could deliver AChE reactivator (obidoxime) across the BBB to act against paraoxon (POX) poisoning. The aptamer had strong affinity for TfR and was modified with 3'-inverted deoxythymidine (dT) to improve serum stability. The uptake of Apt-LP by bEnd.3 cells was significantly higher than that of non-targeting liposomes. The ability of Apt-LP to penetrate intact BBB was confirmed in in vitro BBB mice model and in vivo biodistribution studies. Treatment of POX-poisoned mice with Apt-LP-LuH-6 reactivated 18% of the brain AChE activity and prevented brain damage to some extent. Taken together, these results showed that Apt-LP may be used as a promising brain-targeted drug delivery system against OPs toxicity.

Background: Recent studies have demonstrated that endometrial DNA methylation is essential for embryo implantation during early pregnancy. Dnmt3a is one of the key enzymes for DNA methylation and could be expressed in the endometrium regularly at this stage. Objective and Methods: In this study, we conditionally ablated uterine Dnmt3a using progesterone receptor-cre (Pgrcre) to define the physiological roles of Dnmt3a in female reproduction. Results: We found that ovarian function was not apparently altered and the number of embryo implantation sites in Dnmt3aloxP/loxP Pgrcre/+ (cKO) was not significantly varied during early pregnancy. Western blotting and immunohistochemistry results showed no difference in expression or location of the estrogen receptor α (ERα) and mucin 1 (Muc1), the marker of uterine receptivity. Although the expression of decidual markers, matrix metalloproteinase-2 (Mmp2), matrix metalloproteinase-9(Mmp9), and bone morphogenetic protein-2 (Bmp2), was slightly decreased in Dnmt3a cKO females, the gross morphology of mice uteri during decidualization was not significantly influenced. In the artificial induction of the decidualization model, there was also no remarkable difference in visually observed morphology or uterine weight in Dnmt3a cKO. Lastly, a continuous breeding study showed that the fertility of Dnmt3a cKO female mice was not strikingly altered. Conclusion: Overall, these results demonstrated that although some decidual markers are expressed abnormally, conditional knockout of Dnmt3a in the uterus did not significantly affect the endometrial function during embryo implantation; the embryo could implant into the endometrium normally.

Benzo(a)pyrene (BaP) is a well-known environmental endocrine pollutant, which has ovarian toxicity in mammals. Ovarian corpus luteum (CL), as the main source of progesterone synthesis in early pregnant female, requires a large number of mitochondria for energy supply. We previously demonstrated that BaP and its metabolite benzo(a)pyren-7, 8-dihydrodiol-9, 10-epoxide (BPDE) inhibited the ovarian melatonin receptors (MTRs) expression and decreased the levels of estrogen and progesterone during early pregnancy in mice. Emerging researches show that MTRs also exist on mitochondrial membrane and participate in the regulation of mitochondrial function. However, the relationship between BaP, MTRs on mitochondrial membrane and mitochondrial function remains unknown. Consequently, this study focuses on the effect and potential mechanism of BaP on ovarian luteal mitochondrial function during early pregnancy. We found that BaP and its metabolite BPDE decreased MTRs in early pregnant CL and luteinized KGN cells, especially in mitochondria. Furthermore, BaP or BPDE up-regulated the expression of SIRT3, Mfn2 and Drp-1, damaged mitochondrial morphology and decreased the MMP and the ATP levels, thereby causing mitochondrial dysfunction. Notably, activation of the MTRs on mitochondrial membrane by MTRs agonist ramelteon partially alleviated BPDE-induced up-regulation of SIRT3, Mfn2 and Drp-1, reduced mitochondrial fragmentation and enhanced the MMP and the ATP levels, thus restoring the expression of steroid rate-limiting enzymes. Together, these findings firstly proved that BaP and BPDE down-regulate MTRs on mitochondrial membrane, and further injure mitochondrial function in early pregnant rats' CL, which provides a new insight for understanding the exact mechanism of the BaP-induced ovarian toxicity.

Background The increasing use of cerium dioxide nanoparticles (CeO2NPs) in biomedical field has attracted substantial attention about their potential risks to human health. Recent studies have shown that nanoparticles can induce placental dysfunction and even fetal abortion, but a more detailed mechanism of nanoparticles affecting placental development remains elusive. Results Here, we constructed a mouse exposure model with different doses of CeO2NPs (2.5, 4, 5, 7.5, and 10 mg kg−1 day−1, average particle size 3–5 nm), finding that intravenous exposure to pregnant mice with CeO2NPs could cause abnormal placental development. Deposited nanoparticles were able to be observed in the placental trophoblast at doses of 5 and 7.5 mg kg−1 day−1. Diving into molecular mechanisms indicated that CeO2NPs exposure could lead to autophagy activation in placental trophoblast. At the cellular level, exposure to CeO2NPs inhibited the migration and invasion of HTR-8/SVneo and activated the autophagy through mammalian target of rapamycin complex1 (mTORC1) signaling pathway. Furthermore, inhibition of autophagy initiation by 3-Methyladenine (3-MA) partially restored the function of HTR-8/SVneo, while blocking autophagic flow by Chloroquine (CQ) aggravated the functional damage. Conclusions Maternal exposure to CeO2NPs impairs placental development through trophoblast dysfunction mediated by excessive autophagy activation. These results suggested that autophagy dysfunction may be a potential mechanism for the impairment of trophoblast by CeO2NPs exposure. As above, our findings provide insights into the toxicity mechanism to the reproductive system induced by rare-earth nanoparticles exposure. Graphical Abstract

The in-memory approximate nearest neighbor search (ANNS) algorithms have achieved great success for fast high-recall query processing, but are extremely inefficient when handling hybrid queries with unstructured (i.e., feature vectors) and structured (i.e., related attributes) constraints. In this paper, we present HQANN, a simple yet highly efficient hybrid query processing framework which can be easily embedded into existing proximity graph-based ANNS algorithms. We guarantee both low latency and high recall by leveraging navigation sense among attributes and fusing vector similarity search with attribute filtering. Experimental results on both public and in-house datasets demonstrate that HQANN is 10x faster than the state-of-the-art hybrid ANNS solutions to reach the same recall quality and its performance is hardly affected by the complexity of attributes. It can reach 99\% recall@10 in just around 50 microseconds On GLOVE-1.2M with thousands of attribute constraints.

Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that play important roles in gene expression regulation. This study aimed to evaluate the potential role of circRNAs in decidual tissue of patients with early recurrent miscarriage (RM). We constructed circRNA expression profiles in decidual tissue using microarray data. A total of 123 differentially expressed circRNAs, including 78 upregulated and 45 downregulated circRNAs were detected in the early RM group compared with the control group (P

Soluble solids content (SSC) is one of the most important quality attributes affecting the taste and maturity of fresh fruit. In this study, with the cerasus humilis fruit as the research object, a prediction model of soluble solid content (SSC) in cerasus humilis (CH) is established based on visible / near-infrared spectroscopy to explore a nondestructive testing method of the interior quality of CH. The visible / near-infrared spectral info (350-2500nm) of 160 CHs was collected to extract the reflection spectrum, establishing the linear model (PLSR) and non-linear model (LS-SVM) of CH’s spectral info and SSC. The prediction performance and stability of the model were justified using several statistical indicators namely correlation coefficient of the prediction set (Rp), the root mean square error of the prediction set (RMSEP), and the residual predictive deviation (RPD) index. Results showed that multiplicative scatter correction (MSC) was proved to be the best preprocessing method, UVE-CARS was the optimal method of dimension reduction, the quantities of characteristic wavelengths was 10 and the optimal model was UVE-CARS-PLSR, in which Rc is 0.8995, Rp is 0.8579, RMSEC is 0.8897, RMSEP is 0.9059, and RPD is 1.8766, indicating that the redundant data of the original spectrum can be reduced, the wavelength dimensions can be reduced, valid info can be retained and data processing can be simplified as UVE-CARS extracts characteristic wavelengths. Reference and theoretical basis are provided in this research for future research and development of portable detector and online sorting detection of CH internal quality.

Embryo implantation is essential for normal pregnancy. Decidualization is known to facilitate embryo implantation and maintain pregnancy. Uterine stromal cells undergo transformation into decidual cells after embryo attachment to the endometrium. Pyruvate kinase M2 (PKM2) is a rate limiting enzyme in the glycolysis process which catalyzes phosphoenolpyruvic acid into pyruvate. However, little is known regarding the role of PKM2 during endometrial decidualization. In this study, PKM2 was found to be mainly located in the uterine glandular epithelium and luminal epithelium on day 1 and day 4 of pregnancy and strongly expressed in the decidual zone after embryo implantation. PKM2 was dramatically increased with the onset of decidualization. Upon further exploration, PKM2 was found to be more highly expressed at the implantation sites than at the inter-implantation sites on days 5 to 7 of pregnancy. PKM2 expression was also significantly increased after artificial decidualization both in vivo and in vitro. After PKM2 expression was knocked down by siRNA, the number of embryo implantation sites in mice on day 7 of pregnancy was significantly reduced, and the decidualization markers BMP2 and Hoxa10 were also obviously downregulated in vivo and in vitro. Downregulated PKM2 could also compromise cell proliferation in primary endometrial stromal cells and in Ishikawa cells. The migration rate of Ishikawa cells was also obviously suppressed by si-PKM2 according to the wound healing assay. In conclusion, PKM2 might play an important role in decidualization during early pregnancy, and cell proliferation might be one pathway for PKM2 regulated decidualization.

10-23 DNAzyme has been extensively explored as a therapeutic and biotechnological tool, as well as in DNA computing. Faster cleavage or transformation is always needed. The present research displays a rational modification approach for a more efficient DNAzyme. In the catalytic core, amino, guanidinium and imidazolyl groups were introduced for its chemical activation through the adenine base. Among the six adenine residues, A9 is the unique residue that realizes all the positive effects; the 6-amino and 8-position of adenine and the 7-position of 8-aza-7-deaza-adenine could be used for the introduction of the functional groups. A12 is a new choice for catalytic improvement with an 8-substituent. Therefore, more active DNAzymes could be expected by this nucleobase-modified activation approach.

Previous research on the role of insulin has focused on metabolism. This study investigated the effect of insulin on angiogenesis in endometrial decidualization. High insulin-treated mouse model was constructed by subcutaneous injection of insulin. Venous blood glucose, serum insulin, P4, E2, FSH and LH levels in the pregnant mice were detected by ELISA. Decidual markers, angiogenesis factors and decidual vascular network were detected during decidualization in the pregnant mouse model and an artificially induced decidualization mouse model. Tube formation ability and angiogenesis factors expression were also detected in high insulin-treated HUVECS cells. To confirm whether autophagy participates in hyperinsulinemia-impaired decidual angiogenesis, autophagy was detected in vivo and in vitro. During decidualization, in the condition of high insulin, serum insulin and blood glucose were significantly higher, while ovarian steroid hormones were also disordered (P P in vivo and in vitro (P P P

The increasing use of cerium dioxide nanoparticles (CeOHere, we constructed a mouse exposure model with different doses of CeOMaternal exposure to CeO

10-23 DNAzyme is a catalytic DNA molecule capable of cleaving complementary RNA. Its high cleavage efficiency is being pursued by chemical modifications, for realizing its genetic therapeutics potential. The most efficient and nuclease-resistant DNAzyme was obtained in this study combined two modifications - 7-aminopropyl-8-aza-7-deaza-2'-deoxyadenosine (residue 1) at A9 and 3'-inverted deoxythymidine residue (

Uterine deficiency of Dnmt3b impairs decidualization and consequent embryo implantation defects. Recent advances in molecular technologies have allowed the unprecedented mapping of epigenetic modifications during embryo implantation. DNA methyltransferase 3a (DNMT3A) and DNMT3B are responsible for establishing DNA methylation patterns produced through their de novo-type DNA methylation activity in implantation stage embryos and during germ cell differentiation. It was reported that conditional knockout of Dnmt3a in the uterus does not markedly affect endometrial function during embryo implantation, but the tissue-specific functions of Dnmt3b in the endometrium during embryo implantation remain poorly understood to investigate the role of Dnmt3b during peri-implantation period. Here, we generated Dnmt3b conditional knockout (Dnmt3bd/d) female mice using progesterone receptor-Cre mice and examined the role of Dnmt3b during embryo implantation. Dnmt3bd/d female mice exhibited compromised fertility, which was associated with defective decidualization, but not endometrial receptivity. Furthermore, results showed loss of Dnmt3b did not lead to altered genomic methylation patterns of the decidual endometrium during early pregnancy. Transcriptome sequencing analysis of uteri from day 6 pregnant mice identified phosphoglycerate kinase 1 (Pgk1) as one of the most variable genes in Dnmt3bd/d decidual endometrium. Potential roles of PGK1 in the decidualization process during early pregnancy were confirmed. Lastly, the compromised decidualization upon the downregulation of Dnmt3b could be reversed by overexpression of Pgk1. Collectively, our findings indicate that uterine deficiency of Dnmt3b impairs decidualization and consequent embryo implantation defects.

Exposure to benzo (a)pyrene (BaP) has been confirmed to interfere with embryo implantation. As the primary organ of progesterone synthesis during early pregnancy, the ovarian corpus luteum (CL) is essential for embryo implantation and pregnancy maintenance. We previously demonstrated that BaP impaired luteal function, but the molecular mechanism remains unclear. In CL cells, mitochondria are the main sites of progesterone synthesis. Mitophagy, a particular type of autophagy, regulates mitochondrial quality by degrading damaged mitochondria and ensuring the homeostasis of cell physiology. Therefore, the present study investigated the effects and the potential molecular mechanisms of BaP on ovarian mitophagy during early pregnancy. We found that BaP and its metabolite, BPDE, inhibited autophagy and PINK1/Parkin-mediated mitophagy in the pregnant ovaries and luteinized granulosa cell, KGN. Notably, adenine nucleotide translocator 1 (ANT1), a crucial mediator of PINK1-dependent mitophagy, was suppressed by BaP and BPDE both in vivo and in vitro. The inhibition of ANT1 leads to the decrease in the PINK1 bound to the outer membrane of mitochondria and consequently reduces recruitment of Parkin to the mitochondria, which is required for the subsequent clearance of mitochondria. Meanwhile, exposure to BPDE also damaged mitochondrial function, causing the reduction in mitochondrial potential and ATP production. Overexpression of ANT1 in KGN cells partially relieved the inhibition of mitophagy caused by BPDE, restored mitochondrial function and expression of hormone synthesis-associated genes. Collectively, our study firstly clarified that BaP and BPDE suppress mitophagy of CL cells via the ANT1-PINK1-Parkin pathway, which provides a new insight to explore the detailed mechanism of the BaP-induced ovarian toxicity.

Background: Sparganosis, caused by the larval plerocercoid of Spirometra tapeworms, still poses a potential public health hazard in China. Snakes are an important source of infection for human sparganosis; however, insufficient studies on the population genetics of Spirometra isolates from snakes have occurred to date. This study collected 67 Spirometra isolates from snakes, and several definitive hosts (Panthera tigris, Prionailurus bengalensis, Felis silvestris), in 15 geographical locations in Hunan Province of central China. They were identified using a multiplex polymerase chain reaction assay. Next, these isolates’ population genetic diversity and phylogenetic pattern were explored based on mitochondrial cytb and cox1 genes. Results: All Spirometra isolates collected in the Hunan Province belonged to the genotype of the Korean “Spirometra decipiens” (KJ599679). The genetic diversity analysis based on concatenated sequences revealed no distinct genetic structure among Spirometra populations. Conclusions: The phylogenetic analysis supported the distinction between Polish and Chinese Spirometra isolates. The taxonomy of Spirometra spp. remains ambiguous; more morphological and molecular studies are necessary to clarify the systematics of the genus of Spirometra.

Successful embryo implantation requires well-functioning endometrial luminal epithelial cells to establish uterine receptivity. Inadequate uterine receptivity is responsible for approximately two thirds of implantation failures in humans. However, the regulatory mechanism governing this functional process remains largely unexplored. A previous study revealed that the expression of Rictor, the main member of mTORC2, in mouse epithelial cells is increased on the fourth day of gestation (D4). Here, we provide the first report of the involvement of Rictor in the regulation of endometrial receptivity. Rictor was conditionally ablated in the mouse endometrium using a progesterone receptor cre (PRcre ) mouse model. Loss of Rictor altered polarity remodeling and the Na+ channel protein of endometrial cells by mediating Rac-1/PAK1(pPAK1)/ERM(pERM) and Sgk1/pSgk1 signaling, respectively, ultimately resulting in impaired fertility. In the endometrium of women with infertility, the expression of Rictor was changed, along with the morphological transformation and Na+ channel protein of epithelial cells. Our findings demonstrate that Rictor is crucial for the establishment of uterine receptivity in both mice and humans. The present study may help improve the molecular regulatory network of endometrial receptivity and provide new diagnostic and treatment strategies for infertility.

Ethylparaben (EtP) and propylparaben (PrP) are common preservatives and well-known endocrine-disrupting chemicals. Studies have demonstrated that they can reduce female fertility, but the underlying mechanism, especially that on embryo implantation, is still poorly understood. Endometrial decidualization is a critical event for embryo implantation. In this study, we aimed to explore the effects of EtP/PrP on endometrial decidualization. Pregnant mice were dosed daily by oral gavage with EtP at 0, 400, 800 and 1600 mg/kg or with PrP at 0, 625, 1250 and 2500 mg/kg from Day 1 of pregnancy until sacrifice. The results showed that the rate of pregnant mice with impaired embryo implantation, whose number of implantation sites was less than 7, was significantly increased after exposure to 1600 mg/kg EtP or 2500 mg/kg PrP. Further study found that the expression of endometrial decidualization markers HOXA10, MMP9 and PR was significantly downregulated in 1600 mg/kg EtP group and 2500 mg/kg PrP group. Notably, serum oestrogen and progesterone levels were significantly increased, whereas the expression of uterine oestrogen receptor and progesterone receptor was decreased following 1600 mg/kg EtP or 2500 mg/kg PrP exposure. In the breeding test, fewer offspring were found after females were exposed to 1600 mg/kg EtP or 2500 mg/kg PrP in early pregnancy. This demonstrated that exposure to EtP/PrP interfered with embryo implantation by compromising endometrial decidualization in early-stage pregnant mice. Disorders of reproductive hormones and hormone receptor signals could be responsible for impaired decidualization. This study broadened the understanding on the biological safety of EtP and PrP.

Background: Obesity is associated with many adverse effects on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. However, ovarian function in obese women during early pregnancy still needs further assessment. Methods: Obesity was induced in C57BL6/J mice using high-fat diets (HFD) for 12 weeks; In vitro high-fat model was established with KGN cells treated with Oleate acid and Palmitic acid. Ovarian morphology of obese mice in early pregnancy was assessed by Hematoxylin and Eosin staining and its function was assessed using ELISA, Western blotting and Immunohistochemistry. The Oil Red O staining and Transmission electron microscopy were used to detect fatty acid accumulation and specific markers relating to ovarian functional mechanism were assessed by Real time PCR, Western blotting, Lactate detection, ATP detection, Biochemical analyses and ELISA.Results: The results of this study showed that during early pregnancy, the number of corpus luteum, serum estradiol and progesterone levels, and the expression of genes CYP19A1, CYP11A1 and StAR, which are related to steroid biosynthesis, were significantly increased in HFD female mice. HFD-fed mice also showed a significant increase in ovarian lipid accumulation on day 7 of pregnancy. Genes involved in fatty acid synthesis (Acsl4 and Elovl5) and fatty acid uptake and transport (Slc27a4), together with the β-oxidation rate-limiting enzyme (Cpt1a) were significantly upregulated in HFD-fed mice. Specifically, there was abnormal elevation of ATP level and aberrant expression of tricarboxylic acid cycle (TCA) and electron transport chain related genes in the ovary of HFD pregnant mice. Treatment of KGN cells with etomoxir targeting β-oxidation of fatty acid, showed decrease tricarboxylic acid cycle and electron transport chain. The elevated ATP level and the increased estradiol and progesterone levels were reversed. Conclusions: This study indicated that during early pregnancy, high-fat diet and induced-obesity increased fatty acid β-oxidation, which in turn increase the tricarboxylic acid cycle and the electron transport chain, and consequently increases ATP production and ovarian dysfunction.

A series of triaxial compression tests of frozen sandy soil are carried out under five confining pressures (1 MPa, 4 MPa, 6 MPa, 8 MPa and 10 MPa) at –6 °C. By comparing the grain size distribution...

A kind of shaped core-shell structured binder-free ZSM-5 catalyst is prepared by re-crystallization method, from a shaped mixture of ZSM-5 zeolite and pure silica source as a binder. According to the characterization results, it is found that the silica shell, surrounding the ZSM-5 core in the shaped mixture, can be converted into ZSM-5 zeolite phase under the hydrothermal conditions with vapor-solid phase method. In this way, the catalyst with core-shell zeolite structure is consequently formed. The prepared binder-free ZSM-5 catalyst has more micro-pores than the ordinary shaped zeolite with a binder. In addition, its acidity is weakened because of the migration of framework aluminum towards the outer shell layer of ZSM-5 crystals. When applied to the vapor-phase benzene alkylation with ethylene, this catalyst shows an enhanced stability and selectivity compared to the ordinary shaped catalyst. Specially, xylene, a critical by-product formed by side reactions, is greatly suppressed over the shaped core-shell structured binder-free catalyst. In view of its good mechanical strength as well as its extended lifetime, the shaped core-shell structured binder-free ZSM-5 catalyst will be valuable in the practical industrial ethylbenzene production.