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Abstract Background In cancer biology, circRAD18 promotes glucose metabolism, potentially indicating its involvement in glucose metabolism-related disorders, such as gestational diabetes mellitus (GDM). The present study investigated the predictive role of circRAD18 in GDM and its potential adverse effects. Methods A total of 482 women who intended to get pregnant in short-term were enrolled. For those who successfully conceived, plasma samples were collected and followed up until delivery to monitor the occurrence of GDM and its associated adverse events. The accumulation of circRAD18 in plasma was analyzed using RT-qPCR. GDM-free curves and ROC curves were plotted to assess the predictive value of plasma circRAD18 for GDM. Results After admitting 482 female patients, 388 of them achieved pregnancy within half a year. During the follow-up period, 52 cases were diagnosed with GDM. Compared to non-GDM group (n = 336), the GDM group (n = 52) had a lower accumulation level of circRAD18 on the day of pregnancy confirmation. In addition, low levels of circRAD18 accumulation on that day distinguished potential GDM patients from non-GDM cases. The 388 cases were divided into high and low circRAD18 level groups (n = 194). GDM-free curve analysis showed that patients in the low circRAD18 level group had a higher incidence of GDM compared to the high level group (43/194 vs. 9/194). A close association was found between low levels of plasma circRAD18 and hypertension, but not premature delivery, intrauterine death, malformation, intrauterine infection, miscarriage, macrosomia or intrauterine distress. Conclusion The reduction in the accumulation of plasma circRAD18 is predictive of GDM and hypertension in pregnant women.

In the evolving landscape of mixed human-machine driving environments, autonomous vehicles (AVs) confront the challenge of anticipating the lane-changing intentions and subsequent driving trajectories of neighboring vehicles. This capability is essential for optimizing safety, efficiency, and comfort in decision-making processes. This paper introduces a novel hybrid prediction model, the LSTM-GAT-Bilayer-GRU, which leverages deep learning to enhance predictive accuracy and real-time responsiveness in dynamic traffic scenarios. The proposed model consists of two main components: a lane change prediction model (LSTM-GAT) and a trajectory prediction model (G-BiLayer-GRU), to process and predict complex vehicular interactions and environmental dynamics effectively. The efficacy of this integrated model was tested using the HighD dataset for training, validation, and testing purposes. The results of a benchmark analysis indicate that the proposed model demonstrated superior prediction performance and reliability over the Support Vector Machine (SVM), Random Forest (RF), AlexNet and Back-Propagation Through Time (BPTT) in the context of lane change intention recognition. Combining LSTM for temporal data processing with GAT for spatial interaction analysis, along with the GRU’s precise trajectory prediction, achieved the best error evaluation metric and balanced prediction time consuming metric under the six prediction time-interval, marks a substantial advancement in AVs technology. This integration guarantees smooth operation of AVs in intricate driving scenarios, fine-tuning their reactions to bolster road safety and passenger comfort.

IntroductionThe composition of the intestinal microbiome correlates significantly with an animal’s health status. Hence, this indicator is highly important and sensitive for protecting endangered animals. However, data regarding the fungal diversity of the wild Budorcas taxicolor (takin) gut remain scarce. Therefore, this study analyzes the fungal diversity, community structure, and pathogen composition in the feces of wild B. taxicolor.MethodsTo ensure comprehensive data analyses, we collected 82 fecal samples from five geographical sites. Amplicon sequencing of the internal transcribed spacer (ITS) rRNA was used to assess fecal core microbiota and potential pathogens to determine whether the microflora composition is related to geographical location or diet. We further validated the ITS rRNA sequencing results via amplicon metagenomic sequencing and culturing of fecal fungi.Results and discussionThe fungal diversity in the feces of wild Budorcas taxicolor primarily comprised three phyla (99.69%): Ascomycota (82.19%), Fungi_unclassified (10.37%), and Basidiomycota (7.13%). At the genus level, the predominant fungi included Thelebolus (30.93%), Functional_unclassified (15.35%), and Ascomycota_unclassified (10.37%). Within these genera, certain strains exhibit pathogenic properties, such as Thelebolus, Cryptococcus, Trichosporon, Candida, Zopfiella, and Podospora. Collectively, this study offers valuable information for evaluating the health status of B. taxicolor and formulating protective strategies.

The Keap1-Nrf2 signaling pathway is a major regulator of the cytoprotective response, participating in endogenous and exogenous stress caused by ROS (reactive oxygen species). Nrf2 is the core of this pathway. We summarized the literature on Keap1-Nrf2 signaling pathway and summarized the following three aspects: structure, function pathway, and cancer and clinical application status. This signaling pathway is similar to a double-edged sword: on the one hand, Nrf2 activity can protect cells from oxidative and electrophilic stress; on the other hand, increasing Nrf2 activity can enhance the survival and proliferation of cancer cells. Notably, oxidative stress is also considered a marker of cancer in humans. Keap1-Nrf2 signaling pathway, as a typical antioxidant stress pathway, is abnormal in a variety of human malignant tumor diseases (such as lung cancer, liver cancer, and thyroid cancer). In recent years, research on the Keap1-Nrf2 signaling pathway has become increasingly in-depth and detailed. Therefore, it is of great significance for cancer prevention and treatment to explore the molecular mechanism of the occurrence and development of this pathway.

IntroductionThe intestinal tract of animals is a complex and dynamic microecosystem that is inextricably linked to the health of the host organism. Takin (Budorcas taxicolor) is a threatened species, and its gut microbiome is poorly understood. Therefore, this study aimed to analyze the microbial community structure and potential pathogens of takin.MethodsTakin fecal samples were collected from five sites in a nature reserve to ensure the uniformity of sample collection, determine the effects of different geographical locations on gut microbes, and analyze the differences in microbial communities between sites. Subsequently, high-throughput 16S rDNA gene sequencing was performed to analyze the microbial diversity and potential pathogens in the gut; the findings were verified by isolating and culturing bacteria and metagenomic sequencing.Results and discussionThe takin gut microflora consisted mainly of four phyla: Firmicutes (69.72%), Bacteroidota (13.55%), Proteobacteria (9.02%), and Verrucomicrobiota (3.77%), representing 96.07% of all microorganisms. The main genera were UCG-005 (20.25%), UCG-010_unclassified (12.35%), Firmicus_unclassified (4.03%), and Rumino coccsea_unclassified (3.49%), while the main species were assigned to Bacteria_unclassified. Potential pathogens were also detected, which could be used as a reference for the protection of takin. Pseudomonas presented the highest abundance at Shuichiping and may represent the main pathogen responsible for the death of takin at the site. This study provides an important reference for investigating the composition of the bacterial community in the intestine of takin.

Exosomes have the ability to transport RNA/miRNAs and possess immune modulatory functions. Heat stress, a significant limiting factor in the poultry industry, can induce oxidative stress and suppress the immune responses of laying hens. In this study, we investigated the expression profiles of serum exosomes and their miRNAs in Roman laying hens who were fed a diet with either 0 or 200 mg/kg curcumin under heat stress conditions. The numbers of exosomes were significantly higher in both the HC (heat stress) and HT (heat stress with 200 mg/kg curcumin) groups compared to the NC (control) group and NT (control with 200 mg/kg curcumin) group (p < 0.05). Additionally, we observed that the most prevalent particle diameters were 68.75 nm, 68.25 nm, 54.25 nm, and 60.25 nm in the NC, NT, HC, and HT groups, respectively. From our sRNA library analysis, we identified a total of 863 unique miRNAs; among them, we screened out for subsequent bioinformatics analysis a total of 328 gga-miRNAs(chicken miRNA from the miRbase database). The KEGG pathways that are associated with target genes which are regulated by differentially expressed miRNAs across all four groups at a p-value < 0.01 included oxidative phosphorylation, protein export, cysteine and methionine metabolism, fatty acid degradation, ubiquitin-mediated proteolysis, and cardiac muscle contraction. The above findings suggest that curcumin could mitigate heat-induced effects on laying hens by altering the miRNA expression profiles of serum exosomes along with related regulatory pathways.

Lung cancer is the most diagnosed malignant cancer and the leading cause of cancer-related deaths worldwide, with advanced stage and metastasis being a major issue. The mechanism leading to metastasis is not yet understood. Here, we found that KRT16 is upregulated in metastatic lung cancer tissues and correlated with poor overall survival. Knockdown of KRT16 inhibits metastasis of lung cancer both in vitro and in vivo. Mechanistically, KRT16 interacts with vimentin, and depletion of KRT16 leads to downregulation of vimentin. KRT16 acquired its oncogenic ability by stabilizing vimentin, and vimentin is required for KRT16-driven metastasis. FBXO21 mediates the polyubiquitination and degradation of KRT16, and vimentin inhibits KRT16 ubiquitination and degradation by impairing its interaction with FBXO21. Significantly, IL-15 inhibits metastasis of lung cancer in a mouse model through upregulation of FBXO21, and the level of IL-15 in circulating serum was significantly higher in nonmetastatic lung cancer patients than in metastatic patients. Our findings indicate that targeting the FBXO21/KRT16/vimentin axis may benefit lung cancer patients with metastasis.

PurposeThe aim of the present study was to establish a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the determination of SHR9146, a novel IDO1/TDO dual inhibitor, in mouse plasma and tissues, and to apply it to investigate the preclinical plasma pharmacokinetics and tissue distribution of SHR9146 in mice.MethodsSamples were spiked with deuterated SHR9146-d4 as an internal standard and pretreated by protein-precipitation extraction with methanol. Chromatographic separation was performed on a Venusil ABS C18 column (150 × 4.6 mm, 5 μm) by isocratic elution with 10 mM ammonium acetate buffer containing 0.1% formic acid solution and methanol as mobile phases. MS detection was conducted in positive electrospray ionization with multiple reaction monitoring at m/z 444.1/229.4 for SHR9146 and m/z 448.4/229.2 for the internal standard.ResultsThe method showed good linearity in the calibration range from 0.05 to 50.0 μg/mL. Precisions (intra- and inter-run) were in the range from 0.5% to 5.1%, and accuracies (RE) were between −3.0% and 4.4% for all the concentration levels. SHR9146 was stable in all the tested bio-samples with recoveries >90%. Pharmacokinetic parameters were obtained by non-compartmental analysis. SHR9146 has a half-life of 0.713 h when IV-injected, with CL 12 mL/min/kg and Vd 0.666 L/kg. After oral dosing from 20 to 80 mg/kg, Cmax (range from 8.751 to 12.893 μg/mL) and AUC0-t (range from 15.606 to 69.971 μg·h/mL) of SHR9146 showed dose proportionality. Other post-oral pharmacokinetic parameters in plasma were as follows (n=6): Tmax 0.79 ± 0.36 h, t1/2 1.586 ± 0.853 h, CL 19.8 ± 0.9 mL/min/kg, Vd 3.427± 1.617 L/kg, and absolute bioavailability of 54.2% ± 12.6% (range from 40.2% to 64.7%). In addition, SHR9146 was found to be absorbed rapidly and distributed widely and mainly in the stomach, adrenal gland, liver, and lung.ConclusionThe method was simple, sensitive, accurate, and specific and was successfully applied for the preclinical pharmacokinetic and tissue distribution study of SHR9146 in mice. The results showed that SHR9146 had dose-independent kinetics in mice via oral administration and was absorbed rapidly and distributed widely. The study provides a good basis for further drug development assessment.

This study was conducted to investigate the effects of dietary curcumin on the hepatic lipid metabolism and antioxidant capacity in Roman laying hens. A total of 144 Roman laying hens (28 weeks old) were allocated 4 dietary treatments that included curcumin at concentrations of 0, 50, 150, and 250 mg/kg for 9 weeks. Each treatment had 6 replicates per group with 6 hens per replicate (2 birds/cage). The results showed that dietary supplementation of curcumin decreased (P

The purpose of this study was to examine the effects of high temperature on internal egg yolk quality parameters and their possible mechanisms in Huaixiang chickens. This study consisted of two treatments, and each treatment had six replicates with six birds per cage. A total of seventy-two 26-week-old female Huaixiang chickens were randomly divided into a normal-temperature group (NT) and a high-temperature group (HT) for 6 weeks. And these hens were exposed to 25 ± 2 °C and 32 ± 2 °C, respectively. Their relative humidity was maintained at 55–65%. The results showed that the HT group significantly reduced yolk weight, yolk color, and egg weight compared to the NT group (p < 0.05). Heat stress caused vacuolar degeneration of the liver and reduced the absolute liver weight (p < 0.05). Both yolk triglyceride (TG) and liver TG in the HT group were significantly higher than in the NT group (p < 0.05). However, the liver total cholesterol (TC) level in the HT group was remarkably lower than that in the NT group (p < 0.05). Additionally, heat stress remarkably enhanced SREBP-1c, ACACA, and FASN lipid metabolism-related gene mRNA expression levels in Huaixiang chicken liver after 6 weeks of heat exposure (p < 0.05). Furthermore, the HT group had remarkably reduced total amino acid, Cys, and Tyr levels in the yolk when compared with the NT group in our experiment (p < 0.05). In conclusion, heat stress causes egg yolk quality reduction and abnormal lipid metabolism in Huaixiang chickens. These findings provided novel insights into the role of high temperature on egg yolk parameters and the underlying mechanisms in Chinese indigenous laying hens.

Canthaxanthin(CX) is a ketocarotenoid, which is widely used in poultry production as a lipophilic antioxidant. Huaixiang chickens are a local breed in China famous for their excellent meat quality; improving their laying rate via nutritional regulation has attracted extensive attention. The aim of this study was to evaluate the effects of dietary CX on the laying rate and follicular development in Huaixiang hens. A total of 180 Huaixiang hens were randomly divided into five groups with six replicates, and six chickens per replication. The control group (CON) were fed a basal diet, and the treatment group (NT) were fed a basal diet supplemented with 4, 6, 8 and 10 mg/kg CX. All chickens were 26 weeks old, living at an average environmental temperature of 25 ± 2 °C with a relative humidity of 65–75%. The results showed that supplementing the CX improved the laying rate and large white follicles (LWF) number (p < 0.05) and increased the concentration of reproductive hormones (LH, FSH, E2 and Prog) (p < 0.05), and the basal diet supplemented with 6 mg/kg CX worked best. Moreover, CX could increase the activities of antioxidant enzymes SOD and GSH-Px (p < 0.05) and reduce the content of the lipid peroxidation product MDA in Huaixiang chickens (p < 0.05); again, 6 mg/kg CX was best. In conclusion, dietary CX had positive effects on the laying rate, ovarian structure, reproductive hormone secretion, follicle development, and the antioxidant capacity of Huaixiang hens, and 6 mg/kg CX was recommended to be added to the diet of Huaixiang chickens.

In this paper, based on the Realized GARCH model, the fractional integration Realized GARCH model is proposed by combining long memory parameters with conditional variance and replacing the original realized measure with the realized measure obtained after daily, weekly and monthly weighting. Based on the 5-min high-frequency data of the SSE index, the fractional integration Realized GARCH model, Realized HAR GARCH model and Realized GARCH model are investigated for their fitting effect and predictive ability on market volatility, and Monte Carlo simulations are conducted from the error terms obeying normal distribution, t-distribution and chi-square distribution so as to compare the RMSE and MAE of the three types of models with respect to conditional variance. The empirical results show that the fractionally integrated Realized GARCH model is found to better capture the long-run correlation in volatility in certain intervals by comparing the theoretical and sample auto-correlation functions, while the overall predictive power of the model is better than the other two models. Finally, it provides technical support and suggestions for investors' risk control.

An efficient hub-and-spoke network (HSN) can reduce operating costs and passenger delays at hubs through proper sequencing of flights and assignment of gates. Typically, batches of flights are scheduled to arrive within brief time windows. By considering aircraft sizes/loads and locations of the available gates, there is a considerable potential for reducing the total cost. During pandemic conditions, passenger transfer time and aircraft dwell time significantly increased because of outbreak controls (e.g., COVID-19 and its variant). In addition to walking time between connecting flights, there is a significant delay for the airport staff to validate passengers’ proper travel documents. The objective of this study is to minimize the total cost by optimizing the flight sequencing and gate assignment and by considering the realistic transfer delay under pandemic situations. A genetic algorithm with an elite selection strategy is developed to search for the optimal solution, which significantly reduces the total cost by 25% compared with that under existing operations, and the relations between optimized solutions and various model parameters are explored.

Background: Myeloproliferative neoplasms (MPNs) are a rare yet important clinical cause of portal hypertension, which may cause recurrent gastroesophageal variceal bleeding (GVB). MPN-associated variceal bleeding lacks specific guidelines and clinical consensus and desiderates cohort studies. We performed a multicenter retrospective study to investigate the efficacy of endoscopic management of bleeding in MPNs. Methods: We included consecutive MPN patients with gastroesophageal varices in eight tertiary university hospitals between January 2007 and March 2020. The clinical characteristics of participants were summarized. MPN patients with a history of GVB were followed up for the rebleeding and death, compared with controls suffering from schistosomiasis-associated portal hypertension who received endoscopic treatment for variceal bleeding at the same period. Results: A total of 62 MPN patients with gastroesophageal varices were identified, and 37 had a history of GVB. Of these, 24 patients received endoscopic variceal ligation and endoscopic injection of cyanoacrylate for the prophylaxis of variceal rebleeding. Endoscopic treatment significantly reduced the rebleeding rate in MPN patients with a history of GVB (28.2% versus 68.3%, p = 0.0269). Multivariable Cox regression indicated that endoscopic treatment (HR = 0.10, 95% CI: 0.02–0.54, p = 0.008) was the independent protective factor for decreasing the 3-year rebleeding rate, while the use of non-selective beta-blockers (NSBB) (HR = 13.41, 95% CI: 2.15–83.42, p = 0.005) was the risk factor for increasing the 3-year rebleeding rate. As for the efficacy of endoscopic management, 3-year rebleeding rate was significantly lower in MPN patients in contrast to 46 controls with schistosomiasis-associated variceal bleeding (32.9% versus 59.0%, p = 0.0346). Conclusion: Endoscopic treatment might be a feasible and potent approach in the management of gastroesophageal variceal rebleeding in MPNs, while NSBB might be ineffective.

Subependymal heterotopia (SEH) is a rare neuronal migration disorder consisting of gray matter nodules along the lateral ventricular walls and is often associated with other brain malformations. Despite most SEH cases showing epilepsy during their lifetimes, very few patients with asymptomatically familial SEH tend to cause misdiagnosis or missed diagnosis. We present four familial SEH cases without any positive symptoms and medical history, including two fetuses, who were diagnosed by MRI and confirmed by genetic testing with mutation of filamin A. This report emphasizes the role of MRI in the recognition of SEH at an early age of gestation and in asymptomatically familial SEH. MRI provides a fast, repeatable, reliable, and cheap choice for detecting and screening familial SEH.

Objective: To study the correlation between serum inflammatory factors, oxidative stress factors and frailty, and cognitive frailty in patients with cerebral small vessel disease (CSVD).Methods: A total of 281 patients with CSVD were selected from Tianjin Huanhu Hospital and Inner Mongolia People's Hospital from March 2019 to March 2021. CSVD was diagnosed by MRI. The FRAIL scale was used to evaluate the frailty of patients. Patients with CSVD with frailty and MMSE score

Nrf2 (nuclear factor E2-related factor 2, encoded by Nfe2l2) acts as a master transcriptional regulator in mediating antioxidant, detoxification, and cytoprotective responses against oxidative, electrophilic, and metabolic stress, but also plays a crucial role in cancer metabolism and multiple oncogenic pathways, whereas the redox sensor Keap1 functions as a predominant inhibitor of Nrf2 and, hence, changes in its expression abundance directly affect the Nrf2 stability and transcriptional activity. However, nuanced functional isoforms of Keap1 α and β have rarely been identified to date. Herein, we have established four distinct cell models stably expressing Keap1−/−, Keap1β(Keap1Δ1–31), Keap1-Restored, and Keap1α-Restored aiming to gain a better understanding of similarities and differences of two Keap1 isoforms between their distinct regulatory profiles. Our experimental evidence revealed that although Keap1 and its isoforms are still localized in the cytoplasmic compartments, they elicited differential inhibitory effects on Nrf2 and its target HO-1. Furthermore, transcriptome sequencing unraveled that they possess similar but different functions. Such functions were further determined by multiple experiments in vivo (i.e., subcutaneous tumour formation in nude mice) and in vitro (e.g., cell cloning, infection, migration, wound healing, cell cycle, apoptosis, CAT enzymatic activity, and intracellular GSH levels). Of note, the results obtained from tumourigenesis experiments in xenograft model mice were verified based on the prominent changes in the PTEN signaling to the PI3K-AKT-mTOR pathways, in addition to substantially aberrant expression patterns of those typical genes involved in the EMT (epithelial–mesenchymal transition), cell cycle, and apoptosis.

Multidrug resistance (MDR) of hepatocellular carcinoma (HCC) is a serious problem that directly hinders the effect of chemotherapeutics. In this study, we mainly explore the molecular mechanism of ROS-induced CD13 expression using hepatocarcinoma cells as the research object. We show that the drug of fluorouracil (5FU), epirubicin (EPI) and gemcitabine (GEM) can induce ROS generation, activate Ets2 and promote CD13 expression. Meanwhile, CD13 can activate NRF1 and up-regulate ROS scavenging genes transcription, such as SOD1, GPX1, GPX2 and GPX3, leading to down-regulation of intracellular ROS level and reducing the sensitivity of cells to chemotherapy agent. We also detected the anti-tumor effect of the combination therapy, CD13 inhibitor ubenimex and a variety of conventional anti-cancer drugs, such as 5FU, EPI, GEM, pemetrexed (Pem) and paclitaxel (PTX) were employed in combination. Ubenimex enhances the sensitivity of different chemotherapeutic agents and cooperates with chemotherapeutic agents to suppress tumor growth in vitro and in vivo. In general, overexpression of CD13 can lead to chemotherapy resistance, and CD13 inhibitor can reverse this effect. Combination of chemotherapy agent and ubenimex will become a potential treatment strategy for liver cancer resistance.

The platinum-based, two-drug, 3-week regimen is currently the main first-line chemotherapy program for the treatment of advanced squamous cell lung cancer. The aim of this phase II clinical study was to evaluate the efficacy and adverse events of the bi-weekly program of liposomal paclitaxel combined with nedaplatin as a first-line treatment for advanced squamous cell lung cancer. A total of 52 cases of advanced squamous cell lung cancer were included in this phase II clinical trial. Patients received intravenous infusion of liposomal paclitaxel (100 mg/m2) and nedaplatin (50 mg/m2) on days 1 and 15 of a 4-week cycle. Each patient received two to six cycles of chemotherapy, consistent with the regimen of combined liposomal paclitaxel and nedaplatin. The total effective rate of this chemotherapy program was 37.5%. The median progression-free survival time was 8.5 months (95% confidence interval: 7.8–9.2). The median survival time was 16 months (95% confidence interval: 14.1–17.9). The main adverse event was myelosuppression. Grade 3 leukopenia was noted in seven patients (13.5%), and no grade 4 leukopenia was observed. Grade 3 anemia was noted in four patients (7.7%), and no grade 4 anemia was observed. In addition, no grade 2 or higher thrombocytopenia and no grade 3 or 4 non-bone marrow toxicity was detected. The bi-weekly program of liposomal paclitaxel combined with nedaplatin is effective for the treatment of advanced squamous cell lung cancer, with high safety and few adverse events. However, additional studies are warranted to confirm these results. The trial was registered under the number ChiCTR-OIN-17011423.

Objective: To investigate the effects of gestational diabetes mellitus (GDM) on time to delivery and perinatal outcomes in full-term pregnancies underwent dinoprostone-induced labor. Methods: GDM patients that underwent labor induction with dinoprostone vaginal inserts were retrospectively recruited. Full-term pregnancies with normal glucose tolerance (NGT) that underwent labor induction at the same period were recruited as control. Time to delivery and perinatal outcomes were compared between the two groups. Results: A total of 1555 pregnancies with 226 GDM and 1329 NGT were recruited. GDM pregnancies had older ages, lower gestational age, higher body mass index (BMI) and abortion history, and more multigravida than NGT pregnancies (P< 0.05). Univariate analysis showed no significant difference in time to delivery and delivery rates between the two groups. However, after adjusted in a multivariate analysis model, the delivery rates of GDM women delivered within 12, 24, 36 or 48 h and those vaginally delivered within 12 or 36 h were significantly lower than those in the NGT group (P< 0.05). Perinatal outcomes were clinically similar between the two groups. Conclusion: GDM did not affect the time to delivery, cesarean delivery and other perinatal outcomes in Chinese women underwent dinoprostone-induced labor. However, it may be associated with the lower rates of delivery within different time intervals.

The increased incidence of macrosomia has caused an enormous burden after the transition from the almost 40-year one-child policy to the universal two-child policy in 2015 and further to the three-child policy in 2021 in China. However, studies on risk factors of macrosomia in multipara under the new fertility policy in China are limited. We aim to explore the incidence and risk factors for macrosomia in multipara to provide the scientific basis for preventing macrosomia in multipara. A multi-center retrospective study was conducted among 6200 women who had two consecutive deliveries in the same hospital and their second newborn was delivered from January to October 2018 at one of 18 hospitals in 12 provinces in China. Macrosomia was defined as birth weight ≥ 4000 g. Logistic regression models were performed to analyze risk factors for macrosomia in multipara. The incidence of macrosomia in multipara was 7.6% (470/6200) and the recurrence rate of macrosomia in multipara was 27.2% (121/445). After adjusting for potential confounders, a higher prepregnancy BMI, higher gestational weight gain, history of macrosomia, a longer gestation in the subsequent pregnancy were independent risk factors of macrosomia in multipara (p < 0.05). Healthcare education and preconception consultation should be conducted for multipara patients with a history of macrosomia to promote maintaining optimal prepregnancy BMI and avoid excessive gestational weight gain to prevent macrosomia.

Primary endoscopic hemostasis for bleeding gastrointestinal stromal tumor (GIST) is rarely reported. Herein, we report the case of a patient with a bleeding GIST that was treated with endoscopic obturation with tissue adhesive. A 46-year-old man presented with hematemesis and tarry stool for 1 day. Upper GI endoscopy revealed a bleeding submucosal tumor at the stomach fundus and an exposed pulsatile vessel was seen at the defect. Endoscopic obturation with tissue adhesive was performed to treat the defect and the bleeding was successfully stopped. No recurrence of bleeding was observed through a gastric tube, and 6 days after endoscopic obturation, the patient underwent laparoscopic partial gastrectomy. Endoscopic obturation with tissue adhesive is a feasible and effective method to treat bleeding GIST.

Caroli’s disease (CD) is a very rare congenital disorder that is characterized by non-obstructive, segmental and cystic dilatation of intrahepatic ducts. Most patients with CD are asymptomatic, but some patients may suffer from hepatic fibrosis, liver cirrhosis or/and portal hypertension. In complex CD, cystic dilatations of the intrahepatic bile ducts can be present with congenital hepatic fibrosis, liver cirrhosis, portal hypertension, oesophageal varices and autosomal recessive polycystic kidney disease; a condition known as Caroli’s syndrome. This report describes the case of a 28-year-old woman that had gastro-oesophageal varices that were caused by hepatic fibrosis and portal hypertension as part of Caroli’s syndrome. The patient underwent successful treatment with endoscopic injection sclerotherapy with lauromacrogol and endoscopic variceal obturation using tissue adhesive. There were no immediate complications and the patient remained free of complications at 1-year follow-up. There are no current reports in the published literature describing Caroli’s syndrome induced by gastro-oesophageal varices that were treated by a combination of endoscopic injection sclerotherapy and endoscopic variceal obturation. Endoscopic therapy was an effective technique for the treatment of gastro-oesophageal varices in a patient with Caroli’s syndrome awaiting a liver transplant.

Abstract Background To investigate the effect of different delivery modes and related obstetric factors on the short-term strength of the pelvic floor muscle after delivery in Chinese primipara. Methods A total of 4769 healthy Chinese primiparas at postpartum 6–8 weeks were interviewed. According to the difference of delivery mode, the selected primiparas were divided into 2 groups, including cesarean delivery group containing 2020 and vaginal delivery group containing 2749. All the vaginal deliveries were further divided into 3 groups, including episiotomy group containing 2279, perineal laceration group containing 398, and forceps assisted group containing72. The scales of their pelvic floor muscle (PFM) strengths were examined by specially trained personnel using digital palpation (Modified Oxford scale:0–5 grade). According to participants’ willingness, if the PFM strength was weak (0 or 1 grade), at-home PFM training would be recommended and an electrical stimulation combined with biofeedback therapy would be conducted for them in hospital. Twelve weeks after delivery, the PFM strength would be measured again. For statistical analysis, t-test, one-way variance analysis, Chi-square analysis, Kruskal-Wallis test H, Mann-Whitney U test and Wilcoxon test were carried out. Results The PFM strength in cesarean delivery group was higher than in vaginal delivery group (p 0.05). After accepting PFM training at home and therapy in hospital, 305 women showed increased PFM strength (p

Objective This study aimed to investigate the potential factors that affect the induction to delivery time interval in women undergoing induction of labor with a controlled-release dinoprostone vaginal insert. Methods Pregnant women who presented for delivery at Hubei Maternal and Child Health Hospital from January 2016 to August 2016 were recruited. Finally, 1265 women who underwent labor induction with a vaginal dinoprostone (PGE2) insert were analyzed. Univariate and multivariate linear regression analyses were used to estimate the relevant risks for delivery time. Results Among the1265 subjects, the mean delivery time was 18.92 ± 12.50 hours. Univariate and multivariate analyses showed that fetal weight, an obstetric complication (premature rupture of the membranes), and the delivery history were significantly associated with the induction to delivery time. Biparietal diameter was related to the vaginal delivery time in univariate analysis, but there was no significant difference after adjustment in multivariate analysis. Conclusions Vaginal dinoprostone is an effective method for successful induction of labor. Gestational age, parity, and fetal weight are major factors that predict the induction to delivery time interval.

High-throughput sequencing has identified a large number of sense-antisense transcriptional pairs, which indicates that these genes were transcribed from both directions. Recent reports have demonstrated that many antisense RNAs, especially lncRNA (long non-coding RNA), can interact with the sense RNA by forming an RNA duplex. Many methods, such as RNA-sequencing, Northern blotting, RNase protection assays and strand-specific PCR, can be used to detect the antisense transcript and gene transcriptional orientation. However, the applications of these methods have been constrained, to some extent, because of the high cost, difficult operation or inaccuracy, especially regarding the analysis of substantial amounts of data. Thus, we developed an easy method to detect and validate these complicated RNAs. We primarily took advantage of the strand specificity of RT-PCR and the single-strand specificity of S1 endonuclease to analyze sense and antisense transcripts. Four known genes, including mouse β-actin and Tsix (Xist antisense RNA), chicken LXN (latexin) and GFM1 (G elongation factor, mitochondrial 1), were used to establish the method. These four genes were well studied and transcribed from positive strand, negative strand or both strands of DNA, respectively, which represented all possible cases. The results indicated that the method can easily distinguish sense, antisense and sense-antisense transcriptional pairs. In addition, it can be used to verify the results of high-throughput sequencing, as well as to analyze the regulatory mechanisms between RNAs. This method can improve the accuracy of detection and can be mainly used in analyzing single gene and was low cost.

Agave plants are important crassulacean acid metabolism (CAM) plants with multiple agricultural uses, such as being used in tequila and fiber production. Agave hybrid H11648 ((A. amaniensis Trel. and Nowell × A. angustifolia Haw.) × A. amaniensis) is the main cultivated Agave species for fiber production in large tropical areas around the world. In this study, we conducted a transcriptome analysis of A. H11648. About 49.25 million clean reads were obtained by Illumina paired-end sequencing. De novo assembly produced 148,046 unigenes with more than 40% annotated in public databases, or matched homologs in model plants. More homologous gene pairs were found in Asparagus genome than in Arabidopsis or rice, which indicated a close evolutionary relationship between Asparagus and A. H11648. CAM-related gene families were also characterized as previously reported in A. americana. We further identified 12 cellulose synthase genes (CesA) in Asparagus genome and 38 CesA sequences from A. H11648, A. americana, A. deserti and A. tequilana. The full-length CesA genes were used as references for the cloning and assembly of their homologs in other Agave species. As a result, we obtained CesA1/3/4/5/7 genes with full-length coding region in the four Agave species. Phylogenetic and expression analysis revealed a conserved evolutionary pattern, which could not explain the distinct fiber traits in different Agave species. We inferred that transcriptional regulation might be responsible for Agave fiber development. This study represents the transcriptome of A. H11648, which would expand the number of Agave genes and benefit relevant studies of Agave fiber development.

A substantial fraction of miRNA* species are conserved in animals and can repress activities of target genes. This study aims to investigate the miRNA* species in duck skin by using Solexa sequencing. We obtained a total of 96 miRNA* species in two skin small RNA libraries and identified 56 miRNA/miRNA* (miR/miR*) pairs. Nucleotide bias of miRNA* indicated that the priority was C>A>U>G for the first nucleotide and U>C>A>G for the last nucleotide. Comparison analyses showed that 3′-U accounted for a higher proportion in the 56 miR/miR* pairs. Among the top 20 expressed miRNA* species, 17 were shared by two libraries and most of the miRNA* species were highly conservative, especially in the “seed region”. miR-199a* were expressed highly in our samples, which was also previously shown abundant in mouse hair follicle. Furthermore, four miRNA* species were predicted to target their genes in signal pathways of feather follicle development and feather morphogenesis despite very low levels.

The paper analyzed influence of grid connection of distributed generation on traditional current protection of distribution network, used Matlab/Simulink simulation software to prove influence of different capacities and grid connected positions of distributed generation on each section of current protection of distribution network, and proposed an improved scheme which can meet with protection requirement of distribution network after grid connection of distributed generation. The implementing principle of the scheme is as follows: for downstream protection of distributed generation, taking power supply of power system and distributed generation as a whole, resetting set values of each section of current protection; for upstream protection of distributed generation, installing a direction relay based on fault current component on each protector, so as to ensure reliable action of protection when over-current relay and direction relay start simultaneously.

This research was designed to examine how teachers and students from various cultures (China vs. USA) might present distinct behavioural features in learner-centred classrooms. The findings of the research would serve the purpose to answer the question regarding whether and how learner-centred instruction could better support the learning of students from non-Western cultures. Chinese students experiencing learner-centred instruction (the experimental group), Chinese students from traditional classrooms (the control group), and American students responded to measures assessing their perceived teacher behaviours, and their own learning behaviours along with other two highly relevant variables, namely academic motivation and self-efficacy. The results indicated that Chinese teachers and students in the experimental group presented certain distinct behavioural features in comparison to both control group and American group. It suggested that the implementation of learner-centred instruction brought certain behavioural changes for Chinese teachers and students. However, on the other hand, their behavioural changes were not completely consistent with expectations. For instance, Chinese teachers in the experiment group did not present better performance in empowerment and individualized instruction, and their students did not exhibit more autonomous and self-directed learning behaviours as expected. The implications of the research were discussed in the paper.

To precisely simulate the path of crack growth, a simulation of crack growth progress has been presented by using the redevelopment function of ANSYS APDL and introducing the random criterion of crack propagate directions with critical plane approach. Based on the C(T) specimen test, extract the stress fields of crack tips, and set reasonable simulation parameters to verify the simulation method. The result shows that the initiation site and propagation path of crack are basically anastomoses to the results of test, which make a guiding function for preventing the accidents of crack growth and making anti crack plan.

Cell proliferation is critical to the outgrowth of biological structures including the face and limbs. This cellular process has traditionally been studied via sequential histological sampling of these tissues. The length and tedium of traditional sampling is a major impediment to analyzing the large datasets required to accurately model cellular processes. Computerized cell localization and quantification is critical for high-throughput morphometric analysis of developing embryonic tissues. We have developed the Incremental Cell Search (ICS), a novel software tool that expedites the analysis of relationships between morphological outgrowth and cell proliferation in embryonic tissues. Based on an estimated average cell size and stain color, ICS rapidly indicates the approximate location and amount of cells in histological images of labeled embryonic tissue and provides estimates of cell counts in regions with saturated fluorescence and blurred cell boundaries. This capacity opens the door to high-throughput 3D and 4D quantitative analyses of developmental patterns.

Abstract Background We have previously reported that inhibition of astrocytic activation contributes to the analgesic effects of intrathecal ketamine on spinal nerve ligation (SNL)-induced neuropathic pain. However, the underlying mechanisms are still unclear. c-Jun N-terminal kinase (JNK), a member of mitogen-activated protein kinase (MAPK) family, has been reported to be critical for spinal astrocytic activation and neuropathic pain development after SNL. Ketamine can decrease lipopolysaccharide (LPS)-induced phosphorylated JNK (pJNK) expression and could thus exert its anti-inflammatory effect. We hypothesized that inhibition of astrocytic JNK activation might be involved in the suppressive effect of ketamine on SNL-induced spinal astrocytic activation. Methods Immunofluorescence histochemical staining was used to detect SNL-induced spinal pJNK expression and localization. The effects of ketamine on SNL-induced mechanical allodynia were confirmed by behavioral testing. Immunofluorescence histochemistry and Western blot were used to quantify the SNL-induced spinal pJNK expression after ketamine administration. Results The present study showed that SNL induced ipsilateral pJNK up-regulation in astrocytes but not microglia or neurons within the spinal dorsal horn. Intrathecal ketamine relieved SNL-induced mechanical allodynia without interfering with motor performance. Additionally, intrathecal administration of ketamine attenuated SNL-induced spinal astrocytic JNK activation in a dose-dependent manner, but not JNK protein expression. Conclusions The present results suggest that inhibition of JNK activation may be involved in the suppressive effects of ketamine on SNL-induced spinal astrocyte activation. Therefore, inhibition of spinal JNK activation may be involved in the analgesic effects of ketamine on SNL-induced neuropathic pain.

Abstract Background Neuropathic pain is an intractable clinical problem. Intrathecal ketamine, a noncompetitive N--methyl-D-aspartate receptor (NMDAR) antagonist, is reported to be useful for treating neuropathic pain in clinic by inhibiting the activity of spinal neurons. Nevertheless, emerging studies have disclosed that spinal astrocytes played a critical role in the initiation and maintenance of neuropathic pain. However, the present clinical therapeutics is still just concerning about neuronal participation. Therefore, the present study is to validate the coadministration effects of a neuronal noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine and astrocytic cytotoxin L-α-aminoadipate (LAA) on spinal nerve ligation (SNL)-induced neuropathic pain. Results Intrathecal ketamine (10, 100, 1000 μg/kg) or LAA (10, 50, 100 nmol) alleviated SNL-induced mechanical allodynia in a dose-dependent manner respectively. Phosphorylated NR1 (pNR1) or glial fibrillary acidic protein (GFAP) expression was down-regulated by intrathecal ketamine (100, 1000 μg/kg) or LAA (50, 100 nmol) respectively. The combination of ketamine (100 μg/kg) with LAA (50 nmol) showed superadditive effects on neuropathic pain compared with that of intrathecal administration of either ketamine or LAA alone. Combined administration obviously relieved mechanical allodynia in a quick and stable manner. Moreover, down-regulation of pNR1 and GFAP expression were also enhanced by drugs coadministration. Conclusions These results suggest that combining NMDAR antagonist ketamine with an astrocytic inhibitor or cytotoxin, which is suitable for clinical use once synthesized, might be a potential strategy for clinical management of neuropathic pain.