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Objective. To investigate the efficacy of fluorouracil (FU) combined with paclitaxel (PTX) and oxaliplatin (OXA) as the first-line treatment for advanced gastric signet ring cell carcinoma (SRCC) and its influence on human epidermal growth factor receptor 2 (HER-2) expression. Methods. We collected one hundred and sixty-eight patients with advanced gastric SRCC, including 87 patients treated with FU combined with PTX and OXA as the study group (SG) and 81 patients treated with FU combined with OXA as the control group (CG). We compared indicators such as efficacy and adverse reactions after treatment between the two groups and also detected serum HER-2 expression pre- and post-treatment. Results. The incidence of adverse reactions differed insignificantly between SG and CG P > 0.05 . SG presented a notably higher objective response rate (ORR) and disease control rate (DCR) than that of CG P < 0.05 . After treatment, the serum HER-2 expression level of patients in both groups decreased significantly P < 0.05 , and that in SG was significantly declined compared to CG P < 0.05 . HER-2 was negatively correlated with the efficacy of both SG and CG. The 1-year survival rate in SG (29.89%) was significantly higher than that in CG (16.05%) P < 0.05 . The median OS and PFS were higher in DG than that in CG P < 0.05 . Conclusion. FU combined with PTX and OXA can effectively improve the efficacy of first-line treatment for advanced gastric SRCC while reducing HER-2 expression, without increasing the adverse reaction rate. This treatment is worthy of clinical promotion.

This study analyzes the impact of financial inclusion on economic growth in 104 developing countries from 2004–2019. We construct a novel composite financial inclusion index and apply the dynamic panel estimation technique to examine the impact of financial inclusion. The results indicate that financial inclusion positively correlates with economic growth in developing countries but not in high-income countries. This study shows that financial inclusion affects economic growth primarily by expanding opportunities for lower-income people. With increased financial access, those in the lower-income bracket can expand their economic activity, which results in economic growth in developing countries. In high-income countries, access to financial services is already high, and financial inclusion may not offer new opportunities to a larger segment of the population. The study also compares financial inclusion and financial development. The results suggest that financial inclusion contributes to financial development in developing countries by enhancing access to financial services. The findings recommend that policymakers in developing countries may use financial inclusion to increase economic growth.

A small A-cation in the ALaLiTeO6:Mn4+ phosphors leads to a compact structure and MnO6-octahedron, further resulting in a redshift in luminescence spectra and a remarkable enhancement in quantum efficiency and thermal stability.

Background Acute spontaneous intracerebral hemorrhage (sICH) is a morbid and deadly form of stroke. The lymphocyte-to-monocyte ratio (LMR) and systemic immune-inflammation index (SII) are two novel markers of systemic inflammation. We aimed at investigating the predictive value of LMR and SII in patients with sICH. Methods We retrospectively evaluated patients who were hospitalized for sICH at the First Affiliated Hospital of Zhengzhou University from September 2019 to July 2020. According to the 3-month modified Rankin Scale (mRS) score, we considered a good prognosis group (mRS: 0–2) and a poor prognosis group (mRS ≥ 3 or death). A logistic regression analysis was used to identify the factors affecting the prognosis at 3 months. Results A total of 171 patients with sICH were enrolled. A lower LMR measured at 24 h of admission was an independent predictor of 3-month prognosis (OR: 0.392, 95% CI 0.281–0.547, p Conclusions In patients with sICH, LMR showed an independent predictive value for anticipating 3-month prognosis.

Hybrid male sterility (HMS) is a reproductive isolation mechanism limiting the formation of fertile offspring through interspecific fertilization. Cattleyak is the interspecific hybrid presenting significant heterosis in several economic traits, but HMS restricted its wide reproduction in cettleyak breeding. In this study, we detected the specifically expressed genes of a variety of cells (undifferentiated spermatogonia, primary spermatocytes, secondary spermatocytes, haploid spermatids, sperm, Sertoli cells, Leydig cells, and macrophages) in the testis of yak and cattleyak, and found that the spermatogenesis of cattleyak might be blocked at meiosis I, and the expression of niche factors (NR5A1, GATA4, STAR, CYP11A1, CD68, TNF, and CX3CR1) in undifferentiated spermatogonia niche was abnormal. Then we isolated the undifferentiated spermatogonia and Sertoli cells from yak and cattleyak by enzyme digestion, and detected the specific genes in the two bovid testicular cells as well as the proliferation capacity of the undifferentiated spermatogonia. These results indicated that weak proliferation ability and scarce number of undifferentiated spermatogonia and abnormal gene expressions in Sertoli cells may contribute to male sterility of cattleyak.

Background: Sleep–wake disturbance is prevalent in patients with liver cancer, but there is no direct evidence of its association and related biological mechanisms. Our study was to assess quality of sleep and to describe prevalence of sleep disturbances in patients with different etiologies of liver cancer, especially to explore whether sleep quality influences immune factors. Methods: A total of 210 patients with liver cancer from August 2015 to December 2015 were randomly divided into two groups including HBV cirrhosis and non-HBV cirrhosis. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate their sleep quality, and then 202 patients enrolled in this study were divided into two groups according to their PSQI scores: PSQI ≤ 5 and PSQI > 5. The association between sleep disturbances and immune factors was analyzed by logistic regression models. Results: A total of 56.9% of liver cancer patients experienced poor sleep quality (PSQI > 5). The prevalence of sleep disturbances was significantly higher in patients with liver cancer of non-hepatitis B virus (HBV) cirrhosis than with that evolving from HBV cirrhosis (66.7% vs. 50%, p = 0.018). In non-HBV cirrhosis liver cancer patients, the PSQI > 5 group had a higher percentage of CD3+ T cells (71.06 ± 11.07 vs. 63.96 ± 14.18, p = 0.014) and lower natural killer (NK) cells (14.67 ± 9.65 vs. 20.5 ± 10.77, p = 0.014) compared with patients with PSQI ≤ 5. Logistic regression further confirmed that liver cancer patients without HBV cirrhosis are more prone to experience poor sleep with increased CD3+ T cells (OR = 1.07, 95% CI = 1.01–1.13, p = 0.030) and decreased NK cells (OR = 0.92, 95% CI = 0.85–0.98, p = 0.014). Our results indicate that increased CD3+ T cells and decreased NK cells are both associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis. Conclusions: Most liver cancer patients suffer from sleep disturbances, especially evolving from non-HBV cirrhosis. A rise in CD3+ T cells and a reduction in NK cells are associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis.

Sketch-based 3D shape retrieval (SBSR) is an important yet challenging task, which has drawn more and more attention in recent years. Existing approaches address the problem in a restricted setting, without appropriately simulating real application scenarios. To mimic the realistic setting, in this track, we adopt large-scale sketches drawn by amateurs of different levels of drawing skills, as well as a variety of 3D shapes including not only CAD models but also models scanned from real objects. We define two SBSR tasks and construct two benchmarks consisting of more than 46,000 CAD models, 1,700 realistic models, and 145,000 sketches in total. Four teams participated in this track and submitted 15 runs for the two tasks, evaluated by 7 commonly-adopted metrics. We hope that, the benchmarks, the comparative results, and the open-sourced evaluation code will foster future research in this direction among the 3D object retrieval community.

This study offers a bibliometric analysis of research trends in task-based language teaching (TBLT) from 1985 to 2020. The analysis covers research questions related to the publication trends, venues for publication, productive authors, highly cited articles and references and, more importantly, the most frequently explored TBLT-related topics and their developmental patterns across the past 35 years. Results showed that TBLT was still mostly approached from the traditional cognitive-interactionist and psycholinguistic perspectives with a focus on tasks, individuals (i.e., learners and teachers), task-related variables (e.g., task complexity and task repetition), task performance, and the resultant linguistic forms. While this field of research has witnessed a growing interest in learners’ individual differences and computer-mediated, technologies-assisted learning, a decreasing trend has been observed in topics related to error and recast. Implications for task-based research, pedagogy, and research methodologies are discussed.

Tumor-associated macrophages (TAMs) play an important role in tumor growth and metastasis. However, the involvement of TAMs infiltration in pulmonary osteosarcoma (OS) metastasis remains poorly understood. Therefore, the effect of OS cells on macrophages migration was investigated by in vivo and in vitro experiments to evaluate the infiltration and mechanism of TAMs in pulmonary OS metastases. The results showed that the zinc finger protein ZIM3 was upregulated in OS cells than in osteoblasts and activated the expression of CCL25, which subsequently promoted the migration of M2 macrophages. CCL25 or ZIM3 silencing in OS cells inhibited the infiltration of M2 macrophages and the formation of pulmonary metastatic nodules in a mouse model of pulmonary OS metastasis and prolonged the survival of the mice. Furthermore, bioinformatics analyses revealed that CCL25 and ZIM3 expressions are negatively correlated with the prognosis of OS patients. In conclusion, this study found that a large number of M2 TAMs were recruited into pulmonary metastatic nodules of OS through the activation of the ZIM3-CCL25 axis in OS cells, thereby facilitating OS metastasis. Therefore, the suppression of ZIM3-CCL25-induced recruitment of M2 TAMs to the metastatic sites might be considered as a therapeutic approach to inhibit the growth of pulmonary OS metastases.

In this study, while aiming at the prevention of fire accidents in underground commercial streets, an underground commercial street is selected as a research object, and the building fire is numerically simulated using the PyroSim software. Fire simulation scenarios are divided according to different fire zones by analyzing the temperature, carbon monoxide (CO) concentration, and visibility in the smoke layer inside a building. The available safe evacuation time is calculated according to the critical fire hazard judgment conditions. We found that the time when the flue gas temperature and CO concentration reached the critical value in the fire site was longer than the time when the visibility reached the critical value reducing or even avoiding the spread of smoke from the fire area to the evacuation stairs can provide effective help for crowd evacuation. Finally, the safety of the building is evaluated, and fire prevention countermeasures are defined based on the actual situation and fire numerical simulation results to reduce fire incidence, casualties, and economic losses.

The purpose of this study was to explore the establishment of an auxiliary scoring model for patients with acute pulmonary embolism (APE) complicated with atrial fibrillation (AF) based on random forest (RF) and its application effect. A retrospective analysis was performed on the general data, underlying diseases, laboratory indicators, and cardiac indicators of 100 patients with APE admitted to our hospital from 2018 to 2021. The occurrence of atrial fibrillation in patients with pulmonary embolism was taken as a categorical variable, and the general data, underlying diseases, laboratory indicators, and cardiac indicators were taken as input variables. Then, the risk auxiliary scoring model for patients with APE complicated with AF was established based on RF and logistic regression. Finally, the accuracy, sensitivity, specificity, recall rate, accuracy, F1 value, and the receiver operator characteristic (ROC) curve were used to evaluate the predictive value of the models. After statistical analysis, the optimal node value was 3 and the optimal number of decision trees was 500 in the RF model. The importance of predictors in descending order were Hcy, diabetes mellitus, FT3 level, UA level, left atrial diameter, hypertension, and smoking history. The prediction accuracy of the RF model was 0.934, sensitivity 0.966, specificity 0.876, recall rate 0.9660, accuracy 0.934, and F1 value 0.950. The logistic regression model prediction accuracy was 0.816, sensitivity 0.915, specificity 0.125, recall rate 0.902, accuracy 0.811, and F1 value 0.896. The RF model and logistic regression prediction model AUC values were 0.984 and 0.883, respectively. From this, we conclude that the RF model was better than the logistic regression model in predicting AF in APE patients. So, the RF model had the clinical application value.

Background: SREBP-1c/Insig/SCAP acts as a lipid de novo synthesis pathway, and its factors are highly expressed in the endoplasmic reticulum[4]. At present, this pathway has become a research hotspot in the development of metabolic-associated fatty liver disease. However, there are few studies on how various factors in this pathway change after endoplasmic reticulum stress; in particular, the role of the insulin-inducing gene-1 (Insig-1) has not been elucidated in detail. Objective: To investigate whether liraglutide has a therapeutic effect on rats with T2DM and MAFLD and to further study its possible mechanism Method: rats in the control group and modeling group were fed with normal diet and high-sugar and high-fat diet, respectively . After one month, the mice in the modeling group were injected with 35mg/kg STZ intraperitoneally to establish the model of type 2 diabetes mellitus. T2DM and MAFLD rats were randomly divided into three groups: model group, low dose liraglutide group, and high dose liraglutide group. Fasting blood glucose ,fasting insulin, blood lipid profile, alanine aminotransferase, and aspartate aminotransferase were measured at the end of the 8th week. Paraffin sections were obtained from the same part of the liver of rats in each group and observed by electron microscope after HE staining. Western blot was used to detect the expression of endoplasmic reticulum stress index (GRP78) and negative feedback index of lipid synthesis (Insig-1) in each group. Results: Liver tissue from the drug intervention groups caused a decrease in lipid droplet vacuoles, and the hepatocytes were arranged neatly again. While the expression of GRP78 rose, Insig-1 declined. There were differences with different doses of liraglutide; the higher the dose was, the more obvious the effect. No such changes were observed in T2DM and MAFLD rats after injection of saline. Conclusion: we show that liraglutide may have a therapeutic effect on rats with T2DM and MAFLD by reducing endoplasmic reticulum stress in the liver and increasing the expression of Insig-1.

Catalytic fast pyrolysis (CFP) for biomass treatment is a research hotspot but there is little information about the difference between the in situ and ex situ methods. In present work, the Ni-Fe/CaO-Al

This article reviews selected research on foreign language teaching and learning published in local, high-impact journals in China over the past ten years (2012–2021). A bibliometric analysis was conducted to elicit the most frequently researched topics in the field, which were grouped into four categories, that is, language learning and use, language pedagogy, language learners and teachers, and Teaching English as a Foreign Language approaches/theories, and a number of sub-categories. This was then followed by an in-depth and critical review of 71 studies corresponding to those categories and sub-categories. The review concluded with a discussion of inadequacies and recommendations for future research. It is hoped that a review on the experience of Chinese practitioners and researchers’ efforts to promote foreign language education may contribute to language teaching research and development in the international field.

As a potential selenium-enriched crop, it is of great significance to study the selenium application of Tartary buckwheat. Therefore, to study the effects of selenium application concentration, variety, selenium application period and method on the grain selenium content and yield of Tartary buckwheat, an orthogonal experimental design was used to carry out field experiments in the Jinzhong and Northwest Shanxi ecological regions at the same time. Heifeng 1 and Jinqiao 2 were applied at the branching stage and flowering stage in the Jinzhong, and Heifeng 1 and Jinqiao 6 were applied at the early flowering stage and peak flowering stage in the Northwest Shanxi with different concentrations of sodium selenite (0, 1.37, 2.74, 5.48, 8.22, 12.33, 18.495, 27.7425 g hmThe results showed that the selenium content in Tartary buckwheat grains was positively correlated with the selenium application concentration and increased with increasing selenium application concentration, while the yield of Tartary buckwheat first increased and then decreased with the selenium application concentration. The grain selenium content and yield of Tartary buckwheat were affected by the selenium application concentration, variety and application method.The most effective selenium biofortification program was spraying 2.32 g hm

To determine the association of uric acid (UA) and glucose in aqueous humor with diabetic macular edema (DME) in patients with Type 2 diabetes.Patients with DME or diabetes mellitus without retinopathy were enrolled from August 2016 to December 2020. Nondiabetic patients with age-related cataract or age-related macular degeneration were included as controls.A total of 585 eyes from 585 patients were included for this study. Statistical analysis showed that aqueous UA was associated with central retinal thickness (r = 0.39, P0.0001), with higher levels of UA in severe DME and lower levels in mild DME, suggesting an ocular source of UA from the diabetic retina. Aqueous UA {odds ratio (OR), 6.88 (95% confidence interval [CI], 2.61-18.12)}, but not aqueous glucose (0.95 [95% CI, 0.73-1.23]) or serum UA (0.90 [95% CI, 0.66-1.23]), was a stronger predictor for DME than the duration of DM (1.26 [95% CI, 1.12-1.42]) or hemoglobin A1c (1.35 [95% CI, 0.99-1.83]). If aqueous UA (2.46 mg/dL) and aqueous glucose (6.43 mmol/L) were used as reference, high UA (≥2.46 mg/dL) alone was associated with 5.83-fold increase in risk of DME, but high glucose (≥6.43 mg/dL) alone was not associated with DME.Increased aqueous UA, but not glucose, is an independent risk factor for DME. These data suggest that an intravitreal UA-lowering therapy could be beneficial for DME.

IntroductionGreater amounts of fertilizer are applied every year to meet the growing demand for food. Sugarcane is one of the important food sources for human beings.MethodsHere, we evaluated the effects of a sugarcane—Dictyophora indusiata (DI) intercropping system on soil health by conducting an experiment with three different treatments: (1) bagasse application (BAS process), (2) bagasse + DI (DIS process), and (3) the control (CK). We then analyzed soil chemistry, the diversity of soil bacteria and fungi, and the composition of metabolites to clarify the mechanism underlying the effects of this intercropping system on soil properties.Results and discussionSoil chemistry analyses revealed that the content of several soil nutrients such as nitrogen (N) and phosphorus (P) was higher in the BAS process than in the CK. In the DIS process, a large amount of soil P was consumed by DI. At the same time, the urease activity was inhibited, thus slowing down the loss of soil in the DI process, while the activity of other enzymes such as β-glucosidase and laccase was increased. It was also noticed that the content of lanthanum and calcium was higher in the BAS process than in the other treatments, and DI did not significantly alter the concentrations of these soil metal ions. Bacterial diversity was higher in the BAS process than in the other treatments, and fungal diversity was lower in the DIS process than in the other treatments. The soil metabolome analysis revealed that the abundance of carbohydrate metabolites was significantly lower in the BAS process than in the CK and the DIS process. The abundance of D(+)-talose was correlated with the content of soil nutrients. Path analysis revealed that the content of soil nutrients in the DIS process was mainly affected by fungi, bacteria, the soil metabolome, and soil enzyme activity. Our findings indicate that the sugarcane–DIS intercropping system can enhance soil health.

Nowadays, studies on genetic by environment interactions (G×E) are receiving increasing attention because of its theoretical and practical importance in explaining individual behavioral traits. Use information from different environments to improve the statistical power of genome-wide association and prediction in the hope of obtaining individuals with better breeding value is the most expedient way. However, there are significant challenges when performing genome-wide association studies (GWAS) and genomic selection (GS) using multiple environments or traits, mainly because most diseases and quantitative traits have numerous associated loci with minimal effects. Therefore, this study constructed a new genotype design model program (GbyE) for genome-wide association and prediction using Kronecker product, which can enhance the statistical power of GWAS and GS by utilizing the interaction effects of multiple environments or traits. The data of 282 maize, 354 yaks and 255 peaches were used to evaluate the power of the model at different levels of heritability and genetic correlation. The results show that GbyE can provide higher statistical power for the traditional GWAS and GS models in any heritability and genetic correlation, and can detect more real loci. In addition, GbyE has increased statistical power to three Bayesian models (BRR, BayesA, and BayesCpi). GbyE can make full use of multiple environment or trait informations to increase the statistical power of the model, which can help us understand the G×E and provide a method for predicting association loci for complex traits.

Afforestation is an important and effective way to curb wind-sand hazards in the Alxa Desert. However, over-afforestation makes soil drying occur frequently. The formation of a soil drying layer is seriously restricting the effectiveness of vegetation construction and regional ecological stability. To clarify the process of soil desiccation in Haloxylon ammodendron plantations and determine the suitable planting years, a typical H. ammodendron plantation in this area was selected as the research object, and the soil moisture variation characteristics of this sand-fixing vegetation region with vegetation age were analyzed. The analysis results on soil water supply, consumption, and balance showed that the soil water storage in 0–400 cm soil layer of H. ammodendron plantation varies significantly in different ages. The soil water storage in 0–11 years old was the largest, and the soil water supply was greater than the soil water consumption. The soil water storage in profile increased with the increase of precipitation, the soil water storage of H. ammodendron at 11–22 years old increased first and then decreased with precipitation, and the inflexion existed in 16.5 years old. The soil water consumption of H. ammodendron plantation at 22–46 years old was greater than that of soil water supplement, and the soil moisture appeared negative balance continuously. Therefore, to prevent further deterioration of soil moisture ecological environment in the H. ammodendron plantation and to promote the sustainable development of afforestation in desert areas, thinning measures are suggested when the growth period reaches 16.5 years. The research results could provide scientific basis for afforestation and soil dry layer regulation in the Alxa desert.

High spatial resolution soil moisture (SM) mapping is essential for a wide range of applications, especially for precision irrigation and crop management. This work proposes an SM estimation method combined with time series of L-band fully polarimetric synthetic aperture radar (PolSAR) and passive SM products over crop areas. Regarding the challenge of eliminating vegetation canopy scattering on SM estimation, model-based polarimetric decomposition is implemented as a pretreatment step in which the surface scattering component in both HH and VV channels are extracted. Afterward, dual-pol surface scattering information normalization is dealt with the cosine-squared incidence angle normalization method, which makes it possible for SM inversion with multiple tracks and multi-incidence SAR observations. With the time series of normalized surface scattering information, the alpha approximation-based change detection algorithm (AACD) is used for SM estimation. Since the AACD algorithm is reported with an underdetermined problem of parameter solution and the underestimation issue of soil moisture inversion, an extended AACD which incorporates dual-pol (HH and VV) SAR observations, namely the Dual-pol AACD algorithm, is proposed in this study. Besides, the minimum and maximum values of passive microwave soil moisture data of the whole study area and the entire study period are introduced as constraints in Dual-pol AACD when solving the unknown parameters of the real part of the soil dielectric constant. Finally, the obtained time series of soil dielectric constants are converted to volumetric soil water content using dielectric mixing model. 56 sets of collected UAVSAR L-band data with 4 different flight lines (#31603, #31604, #31605, #31606) of Winnipeg, Manitoba, Canada in 2012 (SMAPVEX12) are used to validate the Dual-pol AACD algorithm. Passive microwave SM constraints are collected from Soil Moisture and Ocean Salinity (SMOS) and Advanced Microwave Scanning Radiometer 2 (AMSR-2) products. The performance of the proposed method is evaluated by comparing the in-situ measurements against the soil moisture estimates of wheat, corn, soybeans, bean, and canola fields at different phenological stages. Results show that the proposed method provides an accuracy of RMSE ≤ 6.5 cm3•cm-3 over all the selected crop fields, which is better than that without the introduction of constraints from passive microwave SM products. This work also compares the SM estimation performance using constraints from SMOS and AMSR-2. In addition, SM estimates in different crop fields and growth stages are also provided regarding the variation of crop morphological characteristics and biophysical properties. It concludes that the proposed SM estimation method has great potential for local and global SM mapping in a high resolution with existing and upcoming L-band SAR data, such as ALOS-2 (Japan), LT-1 (China), NISAR (America and India) and Tandem-L (Germany), etc.

Background The fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is one of the most destructive invasive pests causing serious damage to maize crops in China. At present, the use of chemical pesticides is the main method to prevent and control S. frugiperda. However, the excessive use of chemical pesticides not only causes toxicity in humans and animals but also pollutes the environment and causes public harm. In this context, the present study aimed to isolate, identify and evaluate the pathogenicity of the native strain of Metarhizium guizhouense against eggs, larvae and pupae of S. frugiperda under laboratory conditions. Results The fungal isolate was identified as M. guizhouense (Xct1) based on its morphological and molecular characteristics by sequencing ITS, β-tubulin and EF1-α gene. Meanwhile, the fungal isolate was highly pathogenic to eggs of the S. frugiperda, at the highest concentration of 1 × 108 spores/ml, the cumulative egg hatching rate was only 8.33% at 10 days post exposure. After 10 days of exposure to the highest concentration of 1 × 108 spores/ml, the LC50 values for the first–fifth larval instars of S. frugiperda were 8.12 × 104, 1.11 × 105, 5.55 × 105, 3.87 × 106 and 1.43 × 107 spores/ml, respectively. Conclusions The pathogenicity of M. guizhouense Xct1 to S. frugiperda larvae gradually decreased with increasing the developmental stages. Metarhizium guizhouense Xct1 was more pathogenic to egg and younger larvae of S. frugiperda. This provides a basis for determining the optimal period of control.

Nodulation is the most efficient nitrate assimilation system in the ecosystem while excessive fertilization increased nitrate inhibition effect, deciphering the nitrate signal transduction mechanism in the process is of the utmost importance. In this study, genome-wide analysis of the GmCEP genes were applied to identify nodulation related CEPgenes, 22 GmCEP family members were identified while GmCEP6 mainly expressed in nodule and significantly responded to nitrate treatment and rhizobium infection, especially in later stages. Overexpression and CRISPR-Cas9 were used to validate its role in nodulation. We found GmCEP6overexpression significantly increased the nodule number while GmCEP6knock out significantly decreased nodule number suggests GmCEP6 function as a positive regulator in soybean nodulation. qRT-PCR shown that alterations in the expression of GmCEP6 affected the expression of marker genes in the Nod factor signaling pathway. Lastly the function of GmCEP6 in nitrate inhibition of nodulation was analyzed, nodule number in the GmCEP6 overexpressed roots significantly increased under nitrogen treatments suggests GmCEP6 functions in resistance to nitrate inhibition. The study will help us understand that GmCEP6 promotes nodulation and participates in the regulation of nitrate inhibition of nodulation, which is of great significance for high efficiency utilization of nitrogen in soybean.

Backgroud: A low number of retrieved oocytes significantly affects the clinical pregnancy rate (CLR) in patients with a poor ovarian response (POR).The aim of this study was to assess the effect of GnRH antagonist（GnRH-ant） pretreatment performed on days 2 to 4 of the menstrual cycle on pregnancy outcomes in women with POR undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Methods: We conducted a retrospective study of 208 women with POR undergoing IVF/ICSI from January 2018 to August 2021. The pretreatment GnRH-ant protocol (study group) comprised 32 patients, and the conventional antagonist protocol (control group) included 176 patients. A propensity-score-matching (PSM) method using nearest neighbour matching at a proportion of 1:3 was performed. After PSM, we compared the pregnancy outcomes of each group. Results: After PSM, there was no significant difference in age, antral follicle count (AFC), AMH level, or gonadotropin (Gn) level between the two groups (P>0.5). There were no significant differences in the number of retrieved oocytes, mature oocytes, normally fertilized oocytes, transferable embryos, and good-quality embryos between the two groups (P>0.05). There were no significant differences in biochemical and clinical pregnancy rates between the two groups (P>0.05). The implantation rate [34.4% (11/32)] and live birth rate [50.0% (8/16)] of the studygroup were higher than those of the control group [15.5% (9/58), P=0.039; 13.8% (4/29), P=0.014]. Conclusions: Treatment with a GnRH antagonist on day 2 to day 4 of the menstrual cycle did not increase the number of retrieved oocytes or the clinical pregnancy rate in women with POR undergoing IVF/ICSI, but it may increase the live birth rate. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800019730.

Glioblastoma (GBM), the most common malignant primary brain cancer in adults, nearly always becomes resistant to current treatments, including the chemotherapeutic temozolomide (TMZ). The long noncoding RNA (lncRNA) TMZ-associated lncRNA in GBM recurrence (lnc-TALC) promotes GBM resistance to TMZ. Exosomes can release biochemical cargo into the tumor microenvironment (TME) or transfer their contents, including lncRNAs, to other cells as a form of intercellular communication. In this study, we found that lnc-TALC could be incorporated into exosomes and transmitted to tumor-associated macrophages (TAM) and could promote M2 polarization of the microglia. This M2 polarization correlated with secretion of the complement components C5/C5a, which occurred downstream of lnc-TALC binding to ENO1 to promote the phosphorylation of p38 MAPK. In addition, C5 promoted the repair of TMZ-induced DNA damage, leading to chemotherapy resistance, and C5a-targeted immunotherapy showed improved efficacy that limited lnc-TALC–mediated TMZ resistance. Our results reveal that exosome-transmitted lnc-TALC could remodel the GBM microenvironment and reduce tumor sensitivity to TMZ chemotherapy, indicating that the lnc-TALC–mediated cross-talk between GBM cells and microglia could attenuate chemotherapy efficacy and pointing to potential combination therapy strategies to overcome TMZ resistance in GBM.See related Spotlight by Zhao and Xie, p. 1372.

Supplementary Figures 1-13 and Supplementary Tables 1-12

Objective: To investigate the clinical significance of Computational Fluid analysis in diagnosing and treating coarctation of aorta after three-dimensional reconstruction of CTA. Methods: The clinical data and imaging data of 40 children with coarctation of aorta and 24 normal children were retrospectively analyzed and summarized, and combined with statistical means and computational fluid dynamics and explored the potential of clinical application. Results: (1) Computational fluid pressure difference and color Doppler pressure difference analysis were performed in 40 children with coarctation of aortic arch and 24 normal children.There was no significant difference (P > 0.05) in fluid pressure between the 40 patients with coarctation group was 63.1 ± 5.1 mmHg compared with its preoperative color ultrasound pressure difference (64.1 ± 5.2 mmHg), whereas there was a significant difference (P Conclusion: Computational fluid dynamics for the diagnosis and treatment of coarctation of aorta is consistent with clinical imaging analysis methods; As a new tool for the diagnosis of coarctation of aorta , Computational fluid dynamics has the same clinical benefits, but also has many advantages that imaging does not have. Its application range is broader. Although the current sample size is not sufficient to develop new diagnostic standards, three-dimensional reconstruction of fluid dynamics analysis can provide a lower cost, less patient pressure, less uncertainty, and more accurate and intuitive assessment of the overall pressure change process of the aortic arch, It has a more comprehensive and systematic guiding significance for the diagnosis and treatment of children with coarctation of aorta.

Objective To investigate the clinical significance of hydrodynamics analysis in diagnosing and treating coarctation of the aorta after three-dimensional reconstruction of CTA. Methods The clinical data and imaging data were retrospectively analyzed for a child with coarctation of the aorta and analyzed using computational fluid dynamics combined with relevant literature. Results Through the computational fluid dynamics analysis after three-dimensional reconstruction of a child with coarctation of arch, the changes in pressure gradient in the main coarctation section of children's aortic path were deeply discussed and analyzed. The pressure in the coarctation section decreased sharply, the relevant values met the diagnostic criteria, and the hemodynamics could be relieved after surgical anastomosis. Reduced risk of postoperative constriction and postoperative hypertension made surgical intervention feasible. If the hemodynamics of a child could not be alleviated after surgical intervention, interventions such as balloon dilatation or stent could be considered. Conclusion Fluid dynamics analysis after three-dimensional reconstruction, under ideal circumstances, could be used to evaluate the overall aortic arch pressure change process more accurately and intuitively with lower cost, less patient pressure, and uncertainty, and has a more comprehensive and systematic guiding significance for the diagnosis and treatment of children with coarctation of the aorta.

Yue-yang Yu,1,2 Mei Yuan,1 Wei-jie Qin,3 Hai-hong Bai,4 Hong-zhuo Liu,2 Jin-jing Che1 1Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, People’s Republic of China; 2Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 3State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing, People’s Republic of China; 4Phase I Clinical Trial Center, Beijing Shijitan Hospital of Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Hong-zhuo Liu, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, People’s Republic of China, Tel/Fax +86 13236637187, Email liuhongzhuo@syphu.edu.cn Jin-jing Che, Beijing Institute of Pharmacology and Toxicology, No. 27 Taiping Road, Beijing, People’s Republic of China, Tel/Fax +86 01066930633, Email chejinjing80@126.comPurpose: Liposomes are nano-scale materials with a biofilm-like structure. They have excellent biocompatibility and are increasingly useful in drug delivery systems. However, the in vivo fate of liposomal drugs is still unclear because existing bioanalytical methods for quantitation of total and liposomal-encapsulated drugs have limits. A novel strategy for liposomal-encapsulated drug separation from plasma was developed via the specific coordinate binding interaction of TiO2 microspheres with the phosphate groups of liposomes.Methods: Liposomal-encapsulated docetaxel was separated from plasma by TiO2 microspheres and analyzed by the UPLC-MS/MS method. The amount of TiO2, pH of the dilutions, plasma dilution factors and incubation time were optimized to improve extraction recovery. The characterization of the adsorption of liposome-encapsulated drugs by TiO2 microspheres was observed by electron microscopy. For understanding the mechanism, pseudo-first and the pseudo-second order equations were proposed for the adsorption process. The study fully validated the method for quantitation of liposomal-encapsulated in plasma and the method was applied to the pharmacokinetic study of docetaxel liposomes.Results: The encapsulated docetaxel had a concentration range of 15– 4000 ng/mL from the plasma sample using a TiO2 extraction method. Successful method validation proved the method was sensitive, selective and stable, and was suitable for quantitation of docetaxel liposomes in plasma samples. Extraction recovery of this method was higher than that of SPE method. As shown in electron microscopy, the liposomes adsorbed on TiO2 microspheres were intact and there was no drug leakage. The study proposed pseudo-first and the pseudo-second order equations to facilitate the adsorption of liposomal drugs with TiO2 microspheres. The proposed strategy supports the pharmacokinetic study of docetaxel liposomes in rats.Conclusion: TiO2 extraction method was stable, reproducible, and reliable for quantitation of encapsulated docetaxel. Because of versatility of lipids, it is expected to a universal bioanalysis method for the pharmacokinetic study of liposomes.Graphical Abstract: Keywords: liposomal-encapsulated drug, docetaxel liposomes, TiO2 microspheres, coordinate binding, bioanalysis

Eczema is one of the common skin diseases in the neonatal period. The purpose of this study was to use Shotgun sequencing technology to analyze and compare the main components of the intestinal flora in the feces of eczema term infants and healthy term infants, and to explore the correlation between the characteristics of the intestinal flora and the incidence of eczema in term infants. There were 10 full-term infants who met the inclusion criteria in the Obstetrics Department of the First People's Hospital of Yancheng City, including 5 cases in the eczema group (group E) and 5 cases in the control group (group C). The fecal samples of the 10 full-term infants were collected at five time points: 0 days (meconium), 7 days, 14 days, 21 days, and 28 days, and the DNA of the fecal samples was extracted. According to the EASI scoring method, the eczema area and severity index of the eczema group were evaluated. The above 50 stool samples were subjected to high-throughput metagenomic sequencing of gut microbiota using Shotgun sequencing technology. SPSS 24.0 software was used to analyze the dynamic changes of Staphylococcus epidermidis, Escherichia coli and Bifidobacterium in feces from 0-28 days and the distribution difference of intestinal flora between the eczema group and the control group, and further explore the content of the above bacteria in the eczema group Correlation with eczema severity. The content and distribution characteristics of Staphylococcus epidermidis, Escherichia coli and Bifidobacterium in the intestinal flora of term infants have a certain correlation with the pathogenesis of eczema.