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Objectives: This study explores the correlation between serum cholesterol, interleukin-10 (IL-10), macrophage migration inhibitory factor (MIF), and post-intracerebral hemorrhage (post-ICH) depression in patients with acute ICH. Methods: 35 patients with acute primary supratentorial ICH were recruited. Serum cholesterol, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC), IL-10, and MIF were measured in the first morning after admission. Additionally, a 24-item Hamilton Depression Scale (HAMD-24) was used to detect depressive symptoms one week after admission. HAMD scores ≥ 8 indicated a diagnosis of post-ICH depression. Results: The levels of TC were significantly lower in ICH patients with depression compared to those without [169.26(139.23–215.67) mg/dL vs. 200.46(182.81–224.74) mg/dL, P = 0.010]. Similarly, levels of LDLC [102.18(78.39–137.28) mg/dL vs. 135.14(120.22–170.63) mg/dL, P = 0.001] and IL-10 [17.56(16.03–22.52) pg/mL vs. 31.17(23.42–37.53) pg/mL, P = 0.001] were also lower in patients with post-ICH depression. Furthermore, the levels of TC (r = -0.433, P = 0.009), TG (r = -0.345, P = 0.043), LDLC (r = -0.549, P = 0.001), and IL-10 levels (r = -0.603, P

Abstract Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio

Background First‐pass successful reperfusion (FPSR), defined as a successful/complete reperfusion achieved after a single thrombectomy pass, is predictive of favorable outcome in patients with acute ischemic stroke with large‐vessel occlusion. It is unknown whether intravenous tirofiban is effective in increasing the rate of FPSR in acute anterior large‐vessel occlusion stroke. Methods and Results Patients who had acute large‐vessel occlusion stroke presenting within 24 hours and underwent endovascular thrombectomy were analyzed from the RESCUE BT (Intravenous Tirofiban for Patients With Large Vessel Occlusion Stroke) clinical trial, of which the main analysis was neutral. The RESCUE BT trial randomized patients to receive either intravenous tirofiban or placebo before endovascular thrombectomy. The primary end point was FPSR, defined as successful reperfusion (extended thrombolysis in cerebral infarction scale 2b50, 2c, or 3) at first thrombectomy attempt. A modified Poisson regression analysis assessed the association between intravenous tirofiban treatment and FPSR. Of 948 enrolled patients, 463 patients were randomized to the tirofiban group and 485 to the placebo group. The mean age was 67 years, and 41.0% of the patients were women. FPSR was achieved more often in the tirofiban group (30.5% versus 23.5%; adjusted risk ratio, 1.24 [95% CI, 1.01–1.51]; P=0.04). FPSR was associated with a favorable shift to lower modified Rankin Scale disability levels at 90 days (common odds ratio, 1.42 [95% CI, 1.08–1.86]; P=0.01). Conclusions In this post hoc analysis of the RESCUE BT trial, treatment with intravenous tirofiban before endovascular thrombectomy was associated with increased FPSR in patients with acute ischemic stroke due to large‐vessel occlusion in the anterior circulation. FPSR was associated with reduced 90‐day levels of disability. Registration URL: http://chictr.org; Unique Identifier: ChiCTR‐INR‐17014167.

Abstract Background The gibberellic acid (GA) inhibitor, uniconazole, is a plant growth regulator commonly used in banana cultivation to promote dwarfing but also enhances the cold resistance in plants. However, the mechanism of this induced cold resistance remains unclear. Results We confirmed that uniconazole induced cold tolerance in bananas and that the activities of Superoxide dismutase and Peroxidase were increased in the uniconazole-treated bananas under cold stress when compared with the control groups. The transcriptome and metabolome of bananas treated with or without uniconazole were analyzed at different time points under cold stress. Compared to the control group, differentially expressed genes (DEGs) between adjacent time points in each uniconazole-treated group were enriched in plant-pathogen interactions, MAPK signaling pathway, and plant hormone signal transduction, which were closely related to stimulus-functional responses. Furthermore, the differentially abundant metabolites (DAMs) between adjacent time points were enriched in flavone and flavonol biosynthesis and linoleic acid metabolism pathways in the uniconazole-treated group than those in the control group. Temporal analysis of DEGs and DAMs in uniconazole-treated and control groups during cold stress showed that the different expression patterns in the two groups were enriched in the linoleic acid metabolism pathway. In addition to strengthening the antioxidant system and complex hormonal changes caused by GA inhibition, an enhanced linoleic acid metabolism can protect cell membrane stability, which may also be an important part of the cold resistance mechanism of uniconazole treatment in banana plants. Conclusions This study provides information for understanding the mechanisms underlying inducible cold resistance in banana, which will benefit the production of this economically important crop.

【Objective】The study was conducted to screen plant growth regulators that could shorten the plant height of banana without affecting the yield, and explore the dwarfing effects of their application times on banana plants. Furthermore, appropriate concentrations of uniconazole were detected for identifying the changes in the activities of several defensive antioxidant enzymes, and the contents of soluble protein, potassium, calcium, magnesium and phosphorus in banana leaves, to further analyze the positive auxiliary effect of uniconazole on banana plant growth in addition to dwarfing effect, which would provide references for the safe and rational use of plant growth regulators in banana production.【Method】The dwarfing effects of several plant growth regulators including uniconazole (XX), paclobutrazol (DX), chlormequat chloride (AZ), mepiquat (JP), compound agents 0802 and 0501 on banana plants were evaluated by root spraying method. The contents of polyphenol oxidase (PPO), superoxide dismutase (SOD), catalase (CAT), phenylalanine ammonia lyase (PAL), soluble protein, potassium, calcium, magnesium and phosphorus in banana leaves were determined after 15, 20 and 25 days of 0.3 g/plant XX treatment.【Result】According to the evaluation standard of dwarfing effect, banana plant could grow normally in the 3-5 level of internode distance after dwarfing. Under one dwarfing treatment, the banana plant heights of XX1, DX1, 0501, XX3, JP2, 0802, AZ1 and JP4 treatments were decreased by 11.67-24.00 cm. The banana plant heights of JP2, DX1, JP4, 0802, AZ1, 0501 and XX3 under two dwarfing treatments were decreased by 29.67-39.00 cm with normal growth. It found that the banana plant height was shortened with the increase of the concentrations and application times of these grow regulators. XX3, 0802 and 0501 treatments could promote the early bud shooting of banana, and the duration periods were 8-19 days earlier than that of the control; The plant shooting was neat. The shooting rate of XX3 under two drarfing and 0802 treatment was 62.01% and 89.32%. The yield per plant showed decreasing trends with the increase of XX concentration. The plant yields of banana were 27.26, 25.62 and 23.45 kg for the one time treatment of XX1, XX3 and XX5, respectively. Of which, the yields per plant of XX3 and XX5 treatment were significantly decreased compared with that of the control (27.45 kg). The yields per plant of banana treated with 0802 and 0501 were 27.37 and 26.99 kg, respectively, and there was no significant difference with that of the control. It was found that the yield performance of banana plants was similar under the two dwarfing treatments of different plant grow regulators. Under the treatment with low concentrations of chlormequat chloride and paclobutrazol, the early shooting of banana could be promoted. Whereas the shooting of banana was delayed when the treating concentration was above 0.2 g per plant, and the plant yield was greatly affected or even reduced. The uniconazole treatment could increase the activities of PPO, CAT and PAL in banana leaves as well as the contents of soluble protein, calcium, magnesium, phosphorus and potassium, and enhance plant resistance.【Conclusion】It is recommended to use uniconazole, compound agents 0802 and 0501 as banana dwarfing agents with concentration ranging of 0.2-0.3 g/plant in banana production, and the newly planted banana could be dwarfed once. Banana is more susceptible to paclobutrazol (DX) and chlormequat chloride (AZ), which are not recommended.

Abstract Background Whether iron intake can affect cardiovascular disease (CVD) and dyslipidemia is controversial. However, few studies have focused on reducing the risk of CVD in people at risk for dyslipidemia. This study explored the linear relationship and possible nonlinear relationship between CVD and dyslipidemia. Methods Dietary data were obtained from the China Health and Nutrition Survey between 2004 and 2015. The survey included 8173 participants older than 18 years. CVD risk was estimated by the Framingham risk score (FRS). Logistic regression analysis was used to determine whether iron intake affects CVD incidence and lipid profiles. The nonlinear association was tested with restricted cubic splines (RCSs). Results For males, higher total iron intake [the fifth quintile (Q) vs. Q1 odds ratio (OR): 0.335, 95% confidence interval (CI): 0.248–0.453], heme iron intake (OR: 0.679, 95% CI: 0.492–0.937) and non-heme iron intake (OR: 0.362, 95% CI: 0.266–0.492) reduced CVD incidence. Heme iron intake increased high low-density lipoprotein cholesterol (LDL-C) (OR: 1.786, 95% CI: 1.226–2.602), high total cholesterol (TC) (OR: 2.404, 95% CI: 1.575–3.669), high triglyceride (TG) (OR: 1.895, 95% CI: 1.423–2.523), and low apolipoprotein A1/apolipoprotein B (ApoA-1/ApoB) risk (OR: 1.514, 95% CI: 1.178–1.945). Moderate non-heme iron intake reduced high-density lipoprotein cholesterol (HDL-C) incidence (Q5 vs. Q1 OR: 0.704, 95% CI: 0.507–0.979). For females, higher total iron intake (Q5 vs. Q1 OR: 0.362, 95% CI: 0.266–0.492) and non-heme iron intake (OR: 0.347, 95% CI: 0.154–0.781) reduced CVD incidence. Heme iron intake increased high LDL-C (OR: 1.587, 95% CI: 1.160–2.170) and high TC incidence (OR: 1.655, 95% CI: 1.187–2.309). Conclusions Men, especially those at risk of developing dyslipidemia, should consume non-heme rather than heme iron to reduce CVD incidence. For women, increased heme iron intake did not reduce CVD incidence. Therefore, women should minimize their heme iron intake to prevent dyslipidemia.

Dark tea refers to a kind of post-fermented product, and its quality and price vary owing to the distinct altitudes at which it grows. In this study, a novel method based on high performance liquid chromatography with a diode-array detector (HPLC-DAD) and an evaporative light scattering detector (HPLC-ELSD) was proposed for the classification of dark teas from distinct altitudes in China. Through implementing a strategy fusing feature-level data to construct a combined dataset, the classification performance of dark teas from distinct altitudes in China was evaluated after preprocessing. The results suggested that, through the feature fusion strategy, the identification accuracy rate increased from

Background In China, the prevalence of severe asthma with eosinophilic phenotype is rising, yet treatment options are limited. Mepolizumab is the first targeted biologic therapy for eosinophilic-driven disease in China. This study (clinicaltrials.gov identifier NCT03562195) evaluated efficacy and safety of mepolizumab in Chinese patients with severe asthma. Methods The phase III, multicentre, randomised, placebo-controlled, double-blind, parallel-group study enrolled patients aged ≥12 years with severe asthma, with two or more exacerbations in the previous year, and on inhaled corticosteroids plus at least one controller medication. Following a 1–4-week run-in, patients were randomised 1:1 to mepolizumab 100 mg or placebo subcutaneously every 4 weeks for 52 weeks. The primary end-point was annualised rate of clinically significant exacerbations (CSEs) through week 52. Secondary end-points were time to first CSE, frequency of CSEs requiring hospitalisation/emergency department visits or hospitalisation over 52 weeks, mean change in St George's Respiratory Questionnaire (SGRQ) total score and pre-bronchodilator forced expiratory volume in 1 s (FEV1) at week 52; safety was evaluated. Results The modified intention-to-treat population included 300 patients. At week 52 with mepolizumab versus placebo, annualised rate of CSEs was 65% lower (0.45 versus 1.31 events per year; rate ratio 0.35, 95% CI 0.24–0.50; p

This study established a residue detection method based on the QuEChERS pre-treatment method and combined it with high-performance liquid chromatography–tandem mass spectrometry to test six herbicides (metamitron, clopyralid, desmedipham, phenmedipham, ethofumesate, and haloxyfop-p-methyl) in sugar beet plants, soil, and roots. The degradation dynamics and terminal residues of each herbicide in sugar beets were analysed. Finally, the dietary risks of various herbicides in sugar beets were evaluated based on the dietary structure of Chinese people, and the risk quotient values were below 100%. Using this detection method, all reagents exhibited good linearity (0.9724 ≤ R2 ≤ 0.9998), The limit of quantification (LOQ) ranged from 0.01 to 0.05 mg/L, the matrix effect ranged from −1.2% to −50%, the addition recovery rate ranged from 77.00% to 103.48%, and the relative standard deviation ranged from 1.61% to 16.17%; therefore, all indicators of this method met the residue detection standards. Under field conditions, the half-lives (t1/2) ranged about 0.65 ∼ 2.96 d and 0.38 ∼ 27.59 d in sugar beet plants and soil, respectively. All herbicides were easily degraded in sugar beet plants and soil (t1/2 < 30 d). The terminal residue amounts in the beet plants, soil, and roots ranged from < LOQ to 0.243 mg/kg. The dietary risk assessment of each pesticide was conducted based on the residual median of the terminal residues and the highest residual values on the edible part of the beetroot. The chronic exposure risk quotient (RQc) and acute exposure risk quotient (RQa) values were < 100%, indicating that the residue of each pesticide in beetroot posed low risks to consumers in China at the recommended dosage.

Abstract Background Diabetes and hyperlipidaemia are both risk factors for coronary artery disease, and both are associated with a high triglyceride-glucose index (TyG index). The TyG index has been presented as a marker of insulin resistance (IR). Its utility in predicting and detecting cardiovascular disease has been reported. However, few studies have found it to be a helpful marker of atherosclerosis in patients with symptomatic coronary artery disease (CAD). The purpose of this study was to demonstrate that the TyG index can serve as a valuable marker for predicting coronary and carotid atherosclerosis in symptomatic CAD patients, regardless of diabetes mellitus and hyperlipidaemia. Methods This study included 1516 patients with symptomatic CAD who underwent both coronary artery angiography and carotid Doppler ultrasound in the Department of Cardiology at Tianjin Union Medical Center from January 2016 to December 2022. The TyG index was determined using the Ln formula. The population was further grouped and analysed according to the presence or absence of diabetes and hyperlipidaemia. The Gensini score and carotid intima-media thickness were calculated or measured, and the patients were divided into four groups according to TyG index quartile to examine the relationship between the TyG index and coronary or carotid artery lesions in symptomatic CAD patients. Results In symptomatic CAD patients, the TyG index showed a significant positive correlation with both coronary lesions and carotid plaques. After adjusting for sex, age, smoking, BMI, hypertension, diabetes, and the use of antilipemic and antidiabetic agents, the risk of developing coronary lesions and carotid plaques increased across the baseline TyG index. Compared with the lowest quartile of the TyG index, the highest quartile (quartile 4) was associated with a greater incidence of coronary heart disease [OR = 2.55 (95% CI 1.61, 4.03)] and carotid atherosclerotic plaque [OR = 2.31 (95% CI 1.27, 4.20)] (P

BackgroundDiabetic cardiomyopathy (DCM) lacks specific and sensitive biomarkers, and its diagnosis remains a challenge. Therefore, there is an urgent need to develop useful biomarkers to help diagnose and evaluate the prognosis of DCM. This study aims to find specific diagnostic markers for diabetic cardiomyopathy.MethodsTwo datasets (GSE106180 and GSE161827) from the GEO database were integrated to identify differentially expressed genes (DEGs) between control and type 2 diabetic cardiomyopathy. We assessed the infiltration of immune cells and used weighted coexpression network analysis (WGCNA) to construct the gene coexpression network. Then we performed a clustering analysis. Finally, a diagnostic model was built by the least absolute shrinkage and selection operator (LASSO).ResultsA total of 3066 DEGs in the GSE106180 and GSE161827 datasets. There were differences in immune cell infiltration. According to gene significance (GS) > 0.2 and module membership (MM) > 0.8, 41 yellow Module genes and 1474 turquoise Module genes were selected. Hub genes were mainly related to the “proteasomal protein catabolic process”, “mitochondrial matrix” and “protein processing in endoplasmic reticulum” pathways. LASSO was used to construct a diagnostic model composed of OXCT1, CACNA2D2, BCL7B, EGLN3, GABARAP, and ACADSB and verified it in the GSE163060 and GSE175988 datasets with AUCs of 0.9333 (95% CI: 0.7801-1) and 0.96 (95% CI: 0.8861-1), respectively. H9C2 cells were verified, and the results were similar to the bioinformatics analysis.ConclusionWe constructed a diagnostic model of DCM, and OXCT1, CACNA2D2, BCL7B, EGLN3, GABARAP, and ACADSB were potential biomarkers, which may provide new insights for improving the ability of early diagnosis and treatment of diabetic cardiomyopathy.

Background Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense race 4 (Foc4), is the most lethal disease of bananas in Asia. Methods To better understand the defense response of banana to Fusarium wilt, the transcriptome and metabolome profiles of the roots from resistant and susceptible bananas inoculated with Foc4 were compared. Results After Foc4 inoculation, there were 172 and 1,856 differentially expressed genes (DEGs) in the Foc4-susceptible variety (G1) and Foc4-resistant variety (G9), respectively. In addition, a total of 800 DEGs were identified between G1 and G9, which were mainly involved in the oxidation-reduction process, cell wall organization, phenylpropanoid biosynthesis, and lipid and nitrogen metabolism, especially the DEGs of Macma4_08_g22610, Macma4_11_g19760, and Macma4_03_g06480, encoding non-classical arabinogalactan protein; GDSL-like lipase; and peroxidase. In our study, G9 showed a stronger and earlier response to Foc4 than G1. As the results of metabolomics, lipids, phenylpropanoids and polyketides, organic acids, and derivatives played an important function in response to Fusarium wilt. More importantly, Macma4_11_g19760 might be one of the key genes that gave G9 more resistance to Foc4 by a lowered expression and negative regulation of lipid metabolism. This study illustrated the difference between the transcriptomic and metabolomic profiles of resistant and susceptible bananas. These results improved the current understanding of host-pathogen interactions and will contribute to the breeding of resistant banana plants.

In this work, novel turned-bearing extrusions (TBE) conducted by using the dies with the single corner and double corner, named SC-TBE and DC-TBE respectively, are developed to introduce additional shear strain during the preparation of AZ31 alloy sheets, which is expected to improve the strengths of sheets. Numerical simulations are conducted to uncover the effect of additional shear deformation on the microstructure during the TBE. The results show that the high strain during the TBE leads to a high nucleation rate for dynamic recrystallization (DRX), resulting in grain refinement of the extruded Mg alloy sheet. However, the high strain also increases the temperature of the material due to the heat generated by plastic deformation, which provides a great driving force for grain growth and consumes dislocations. As these two effects compete with each other when increasing the strain near the die orifice, the SC-TBE sheet has finer grains and a higher residual dislocation density compared to the DC-TBE sheet or the sheet prepared by the conventional extrusion (CE). Fine-grain strengthening and substructure strengthening work together and enhance the tensile yield strength (TYS) of the SC-TBE sheet. The TYSs along extrusion direction (ED), transverse direction (TD) and 45° direction (the half angle between ED and TD) of the SC-TBE sheet are improved by 32 MPa, 65 MPa and 35 MPa respectively compared with the CE sheet. The findings of this research provide some new insights into the development of new preparation methods for Mg alloy sheets with higher strength.

Abstract Background Germline mosaicisms could be inherited to offspring, which considered as “de novo” in most cases. Paternal germline MECP2 mosaicism has been reported in fathers of girls with Rett syndrome (RTT) previously. For further study, we focused on MECP2 germline mosaicism in males, not only RTT fathers. Methods Thirty-two fathers of RTT girls with MECP2 pathogenic mutations and twenty-five healthy adult males without history and family history of RTT or other genetic disorders were recruited. Sperm samples were collected and ten MECP2 hotspot mutations were detected by micro-droplet digital PCR (mDDPCR). And routine semen test was performed at the same time if the sample was sufficient. Additionally, blood samples were also detected for those with sperm MECP2 mosaicisms. Results Nine fathers with RTT daughters (28.1%, 9/32) were found to have MECP2 mosaicism in their sperm samples, with the mutant allele fractions (MAFs) ranging from 0.05% to 7.55%. Only one father with MECP2 c.806delG germline mosaicism (MAF 7.55%) was found to have mosaicism in the blood sample, with the MAF was 0.28%. In the group of healthy adult males, MECP2 mosaicism was found in 7 sperm samples (28.0%, 7/25), with the MAFs ranging from 0.05% to 0.18%. None of the healthy adult males with MECP2 germline mosaicisms were found with MECP2 mosaicism in blood samples. There were no statistical differences in age, or the incidence of asthenospermia between fathers with RTT daughters and healthy adult males with MECP2 germline mosaicisms. Additionally, there was no linear correlation between MAFs of MECP2 mosaicisms and the age of males with germline MECP2 mosaicisms. Conclusions Germline MECP2 mosaicism could be found not only in fathers with RTT daughters but also in healthy adult males without family history of RTT. As germline mosaic mutations may be passed on to offspring which commonly known as “de novo”, more attention should be paid to germline mosaicism, especially in families with a proband diagnosed with genetic disorders.

Cupressus gigantea is an endangered species mainly distributed on beach land, down-slope, and middle-slope positions along the Yarlung Zangbo River on the Tibet Plateau of China, with an altitude ranging from 3000 to 3400 m. We investigated the rhizosphere and fine root microbiomes of C. gigantea at these three slope positions through metagenomic analysis. Slope positions had a greater influence on microbiome composition in the rhizosphere than that in the fine roots. Down- and middle-slope positions presented higher microbial richness indeces and community similarity, while a more complex co-occurrence network was observed in the beach land samples. Rhizosphere bacterial community assembly was determined via deterministic processes in the beach land and via stochastic processes in the down- and middle-slope positions. Archaeal and fungal community assemblies were both dominated by stochastic processes in the rhizosphere and fine roots at the three slope positions. Nitrogen (N) functional genes were more sensitive to changes in slope positions than phosphorus (N) functional genes. Soil properties explained more than 60% and 34% of the variations in the N and P functional genes and more than 30% and 10% of the variations in the microbiomes in the rhizosphere and fine roots, respectively. Variation in the microbiome was significantly driven by total nirtogen, total potassium, pH, and soil moisture in rhizosphere, and by pH and soil moisture in fine roots. Our observations suggest that the effect of slope position on the microbiomes of C. gigantea was greater for the rhizosphere than the fine roots, with down- and middle-slope positions presenting higher community similarity.

The global atmospheric nitrogen (N) deposition has intensified in recent years, resulting in a complex impact on forest ecosystems. This study investigated the effects of canopy (CAN) and understory additions of N (UAN) on leaf carbon (C) and N assimilations, as well as growth parameters of representative woody plant species in an evergreen broad-leaved forest, i.e. Castanea henryi, Schefflera heptaphylla, Blastus cochinchinensis, and Lasianthus chinensis. The results showed that leaf N assimilation key enzyme nitrate reductase (NR) activities of B. cochinchinensis and S. heptaphylla were significantly decreased by UAN, and were significantly decreased by CAN for C. henryi. CAN significantly decreased the nitrite reductase activity of C. henryi, while significantly increased that of L. chinensis. However, the Amax values of each woody species were not significantly different among control (CK), CAN, and UAN. Community surveys demonstrated that CAN and UAN inhibited the growth (diameter at breast height, height, or crown width) of the representative large tree, C. henryi, while promoting the growths of understory woody species (B. cochinchinensis and L. chinensis). Overall, N addition was found to change the physiological processes of N and C metabolisms of the dominant woody species in an evergreen broad-leaved forest. The community of subtropical evergreen broad-leaved forests may further decline and its C fixation capacity may be detrimentally changed under N deposition in the future.

Abstract Background Uniconazole is an effective plant growth regulator that can be used in banana cultivation to promote dwarfing and enhance lodging resistance. However, the mechanisms underlying banana dwarfing induced by uniconazole are unknown. In uniconazole-treated bananas, gibberellin (GA) was downregulated compared to the control groups. An integrative analysis of transcriptomes and metabolomes was performed on dwarf bananas induced by uniconazole and control groups. The key pathways involved in uniconazole-induced dwarfism in banana were determined according to the overlap of KEGG annotation of differentially expressed genes and (DEGs) differential abundant metabolites (DAMs). Results Compared with the control groups, the levels of some flavonoids, tannins, and alkaloids increased, and those of most lipids, amino acids and derivatives, organic acids, nucleotides and derivatives, and terpenoids decreased in uniconazole-treated bananas. Metabolome analysis revealed the significant changes of flavonoids in uniconazole-treated bananas compared to control samples at both 15 days and 25 days post treatment. Transcriptome analysis shows that the DEGs between the treatment and control groups were related to a series of metabolic pathways, including lignin biosynthesis, phenylpropanoid metabolism, and peroxidase activity. Comprehensive analysis of the key pathways of co-enrichment of DEGs and DAMs from 15 d to 25 d after uniconazole treatment shows that flavonoid biosynthesis was upregulated. Conclusions In addition to the decrease in GA, the increase in tannin procyanidin B1 may contribute to dwarfing of banana plants by inhibiting the activity of GA. The increased of flavonoid biosynthesis and the change of lignin biosynthesis may lead to dwarfing phenotype of banana plants. This study expands our understanding of the mechanisms underlying uniconazole-induced banana dwarfing.

Abstract Background Previous studies on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have found that those who died in hospital had higher blood urea nitrogen levels and a worse nutritional status compared to survivors. However, the association between the blood urea nitrogen to serum albumin ratio (BUN/ALB ratio) and in-hospital and short-term prognosis in patients with AECOPD remains unclear. The aim of this study was to explore the usefulness of BUN/ALB ratio in AECOPD as an objective predictor for in-hospital and 90-day all-cause mortality. Methods We recorded the laboratory and clinical data in patients with AECOPD on admission. By drawing the ROC curve for the patients, we obtained the cut-off point for the BUN/ALB ratio for in-hospital death. Multivariate logistic regression was used for analyses of the factors of in-hospital mortality and multivariate Cox regression was used to analyze the factors of 90-day all-cause mortality. Results A total of 362 patients were recruited and 319 patients were finally analyzed. Twenty-three patients died during hospitalization and the fatality rate was 7.2%. Furthermore, 14 patients died by the 90-day follow-up. Compared with in-hospital survivors, patients who died in hospital were older (80.78 ± 6.58 vs. 75.09 ± 9.73 years old, P = 0.001), had a higher prevalence of congestive heart failure(69.6% vs. 27.4%, P

Despite the laminated composite sheets of dissimilar magnesium (Mg) alloys have attracted great attention due to their excellent comprehensive mechanical properties as compared to the sheets of individual alloys, how the structural parameters, especially the layer thickness ratio (LTR), influence their formability is still left unstated in the previous researches. We investigate the effects of LTR on the bendability of the co-extruded laminated composite sheet of Mg alloys, Mg-Al-Zn/Mg-Gd, by combining the V-shaped bending experiments, quasi-in-situ electron backscattered diffraction (EBSD) measurement and finite element (FE) simulations. When the layer Mg-Gd is placed in the outer layer, the bendability of the laminated composite sheet first increases and then decreases, and it reaches the optimum at an LTR (AZ31:Mg-Gd) of 2:1, which goes against the intuition that the higher the volume fraction of the Mg-Gd alloy, the better the bendability. This phenomenon is explained by the competitive effect between the improved plasticity of the outer layer and the enhanced tensive-compressive asymmetry of the outer and inner layers with increasing the thickness of layer Mg-Gd. The neutral layer migrates from the geometrical central layer to the compressive zone due to the asymmetrical responses of the inner and outer layers. Both the shift of the neutral layer and the strain of the outer layer increased by reducing the LTR. It is believed that this research provides some new insights into the design and development of high-formability laminated composite sheets of Mg alloys.

Application of soil nitrogen limitation selective pressure enhanced seed yield and nitrogen use efficiency in the 9th generation of Brassica rapa, likely due to alterations in soil microbiome composition.

This study aimed to clarify the maximum residue limit value of muskmelon, the additional types and their recommended values. Based on the quantitative analysis of 60 pesticide residues in 545 melon samples from 6 provinces in 2018 and 2019, the detected pesticide varieties were evaluated for chronic dietary intake risk (%ADI)，acute dietary intake risk (%ARfD) and risk matrix. The quality and safety risks of pesticide residues in muskmelon were discussed, and the research and analysis on the relatively high risks of pesticide residues and the supplementary types and recommended values of maximum residue limits (MRLs) were carried out. The results showed that the acute and chronic dietary risks of residual pesticides were less than 100%, and the acute dietary risk of pendimethalin was relatively high, reaching 56.67%, among the residual pesticides, pyridaben, emamectin benzoate, and bifenthrin had relatively high risk. And 65.22% of residual pesticides had no MRLs, including 3 residual pesticides with relatively high risks. Based on the above analysis, pyridaben, emamectin benzoate, bifenthrin and pendimethalin had the characteristics of relatively high risk and no maximum residue limit. It was recommended to formulate corresponding limit values. The recommended values were as follows: 1, 0.05, 1, 3 mg·kg−1.

In recent years, environmental problems have become an important bottleneck restricting the sustainable development of Marine economy in China. CO2 is one of the main greenhouse gases which contributes to marine environmental problems. As CO2 emissions can transfer among industries, identifying the industries that release CO2 most and clarifying the carbon emission flows among marine industries are helpful for decision-makers to curb CO2 emissions of marine industries. This paper applies the network method to measure carbon emission flows. First, carbon transfer coefficient is calculated. Second, carbon transfer network of marine industry is constructed based on carbon transfer coefficient. Then the structure of marine industry carbon transfer network is analyzed. Finally, the method proposed in this paper is applied to the case of China and some suggestions for carbon reduction is put forward.

BackgroundLipid storage myopathy (LSM) is an autosomal recessive inherited lipid and amino metabolic disorder with great clinical heterogeneity. Variations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene cause multiple acyl-CoA dehydrogenase deficiency (MADD), and have a manifestation of LSM. Muscle biopsy helps clarify the diagnosis of LSM, and next-generation sequencing (NGS) can be useful in identifying genomic mutation sites. The diagnosis of MADD contributes to targeted therapy.Case presentationWe report on a teenager who appeared to have muscle weakness and exercise intolerance at the onset. Before the referral to our hospital, he was unsuccessfully treated with glucocorticoid for suspected polymyositis. The next-generation sequencing of the proband and his parents revealed heterozygous variations, c.365G>A (p.G122D) inherited from the father, c.176-194_176-193del, and c.832-316C>T inherited from the mother in the ETFDH gene. The tandem mass spectrometry identified the mutations to be pathogenic. However, his parents and his younger sister who were detected with a mutation of c.365G>A presented no clinical symptoms. This indicates that the combination of the three compound heterozygous mutations in ETFDH is significant. After MADD was diagnosed, a dramatic clinical recovery and biochemical improvement presented as riboflavin was given to the patient across a week, which further confirmed the diagnosis of MADD.ConclusionOur observations extend the spectrum of ETFDH variants in Chinese the population and reinforce the role of NGS in diagnosis of MADD. Early diagnosis and appropriate treatment of LSM lead to great clinical efficacy and avoid some lethal complications.

Deficits in responding to joint attention (RJA) are early symptoms of autism spectrum disorder (ASD). Currently, no automated tools exist for identifying and quantifying RJA behaviors. A few eye tracking studies have investigated RJA in ASD children but have produced conflicting results. In addition, little is known about the trajectory of RJA development through developmental age. Here, a new video was designed including 12 clips of an actor pointing to or looking at an object. Eye tracking technology was used to monitor RJA in three groups: 143 ASD children assessed with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) (4–7 years old), 113 age- and gender-matched typically developing children (TDC), and 43 typically developing adults (TDA) (19–32 years old). RJAfinder was developed in R and MATLAB to quantify RJA events from the eye tracking data. RJA events were compared among the three groups. Spearman correlation coefficients between total number of RJA events in ASD and the Social Responsiveness Scale (SRS) scores were calculated. A logistic regression model was built using the average valid sampling rate and the total number of RJA events as two predictive variables to classify ASD and TDC groups. ASD children displayed statistically significantly less RJA events than the TDC and TDA groups with medium-to-large-sized effects. ASD and TDC children both displayed more RJA events in response to pointing stimuli than to looking stimuli. Our logistic regression model predicted ASD tendency with 0.76 accuracy in the testing set. RJA ability improved more slowly between the ages of 4–7 years old in the ASD group than in the TDC group. In ASD children, RJA ability showed negative correlation with SRS total T-score as well as the scores of five subdomains. Our study provides an automated tool for quantifying RJA and insights for the study of RJA in ASD children, which may help improve ASD screening, subtyping, and behavior interventions.

Processing oils are indispensable in the rubber industry. Conventional oils just physically exist in compounds and migrate out of samples over time, which deteriorates the properties of materials and pollutes the environment. In this study, liquid 3,4-polyisoprene (L3,4-IR) has been synthesized, and it can co-cure with matrix to mitigate migration problems. Furthermore, L3,4-IR gives compounds lower Mooney viscosity, reduced Payne effect, and better filler dispersion than conventional treated distillate aromatic extracted (TDAE) oils. Vulcanizates with the high tan δ value at 0 °C and the decreased tan δ value at 60 °C were also obtained using L3,4-IR instead of TDAE oil and commercial liquid polyisoprene or polybutadiene, indicating the better wet-grip and lower rolling resistance properties. Compounds containing L3,4-IR also exhibit higher thermal stabilities and better abrasion resistance than sample containing TDAE oils after thermal aging. The excellent properties obtained in this work make L3,4-IR a strong candidate for developing the next generation of green tires with high performance.

Hypoxia is a major regulator of tumor aggressiveness and metastasis in cancer progression. Exosomes (exos) play an important role in the communication between lung cancer and hypoxic microenvironment. However, the underlying mechanisms are largely undefined. Exos were isolated from A549 cells under hypoxia conditions. Transmission electron microscopy and nanoparticle tracking analysis were carried out to characterize exos. CCK-8 assay, flow cytometry, Western blot, wound healing, and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of A549 cells, respectively. The M2 polarization of macrophages was evaluated by RT-qPCR and Western blot analysis. In vivo nude mice model was established to determine the regulatory effect of hypoxia/exos on the progression of lung cancer. Hypoxic A549 cell-derived exos (hypoxia/exos) promoted the proliferation and migration, and inhibited the apoptosis in A549 cells. The expression of PKM2 was significantly upregulated in hypoxia/exos. Hypoxic exosomal PKM2 induced M2 polarization of macrophages by activating AMPK pathway. Co-culture with hypoxia/exos-treated macrophages enhanced the migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. Moreover, treatment with hypoxia/exos facilitated the tumor growth and lung metastasis of A549 cells. Our findings reveal that hypoxic exosomal PKM2 induces M2 macrophage polarization via AMPK pathway, and thus exerts a simulative effect on the growth and metastasis of lung carcinoma.

As a new generation of green media and functional materials, ionic liquids (ILs) have been extensively investigated in scientific and industrial communities, which have found numerous ap-plications in polymeric materials. On the one hand, much of the research has determined that ILs can be applied to modify polymers which use nanofillers such as carbon black, silica, graphene oxide, multi-walled carbon nanotubes, etc., toward the fabrication of high-performance polymer composites. On the other hand, ILs were extensively reported to be utilized to fabricate polymeric materials with improved thermal stability, thermal and electrical conductivity, etc. Despite substantial progress in these areas, summary and discussion of state-of-the-art functionalities and underlying mechanisms of ILs are still inadequate. In this review, a comprehensive introduction of various fillers modified by ILs precedes a systematic summary of the multifunctional applications of ILs in polymeric materials, emphasizing the effect on vulcanization, thermal stability, electrical and thermal conductivity, selective permeability, electromagnetic shielding, piezoresistive sensitivity and electrochemical activity. Overall, this review in this area is intended to provide a fundamental understanding of ILs within a polymer context based on advantages and disadvantages, to help researchers expand ideas on the promising applications of ILs in polymer fabrication with enormous potential.

In this paper, we study the global structure of nodal solutions of $$ \begin{cases} u''''(x)=\lambda h(x)f(u(x)), & 0 0$ is a parameter, $h\in C([0,1],(0, \infty))$, $f\in C(\mathbb{R})$ and $sf(s)>0$ for $|s|>0$. We show the existence of $S$-shaped component of nodal solutions for the above problem. The proof is based on the bifurcation technique.

Background and ObjectivesAccumulating evidence suggests that oxidative stress is involved in the development of chronic obstructive pulmonary disease (COPD) and its progression. Activity of extracellular superoxide dismutase (ecSOD), the only extracellular enzyme eliminating superoxide radicals, has been reported to decline in acute exacerbations of COPD (AECOPD). However, the association between serum ecSOD activity and 1-year all-cause mortality in AECOPD patients remains unclear. The objective of our study was to explore the usefulness of ecSOD activity on admission in AECOPD as an objective predictor for 1-year all-cause mortality.MethodsWe measured serum ecSOD activity in AECOPD patients on admission in a prospective cohort study. We also recorded their laboratory and clinical data. Multivariate Cox regression was used to analyze the association between ecSOD activity and the risk of 1-year all-cause mortality. Restricted cubic spline curves were used to visualize the relationship between ecSOD activity and the hazard ratio of 1-year all-cause mortality.ResultsA total of 367 patients were followed up for 1 year, and 29 patients died during a 1-year follow-up period. Compared with survivors, the non-survivors were older (79.52 ± 8.39 vs. 74.38 ± 9.34 years old, p = 0.004) and had increased levels of tobacco consumption (47.07 ± 41.67 vs. 33.83 ± 31.79 pack-years, p = 0.037). Having an ecSOD activity ≤ 98.8 U/ml was an independent risk factor of 1-year all-cause mortality after adjustment for baseline differences, clinical variables and comorbidities [hazard ratio = 5.51, 95% confidence interval (CI): 2.35–12.95, p < 0.001].ConclusionLower serum ecSOD activity was a strong and independent predictor of 1-year all-cause mortality in AECOPD patients.

In this paper we study the global bifurcation of sign-changing radial solutions for some semilinear elliptic problems of order 2m in an annulus with Dirichlet boundary conditions.

Abstract We show the global structure of the set of positive solutions of a discrete Dirichlet problem involving the p-Laplacian difference operator suggesting suitable conditions on the weight function and nonlinearity. We obtain existence and multiplicity of positive solutions for λ lying in various intervals in R $\mathbb {R}$ by using the directions of a bifurcation and the Picone-type identity for discrete p-Laplacian operators.

Mosaic variants resulting from postzygotic mutations are prevalent in the human genome and play important roles in human diseases. However, except for cancer-related variants, there is no collection of postzygotic mosaic variants in noncancer disease-related and healthy individuals. Here, we present MosaicBase, a comprehensive database that includes 6698 mosaic variants related to 266 noncancer diseases and 27,991 mosaic variants identified in 422 healthy individuals. Genomic and phenotypic information of each variant was manually extracted and curated from 383 publications. MosaicBase supports the query of variants with Online Mendelian Inheritance in Man (OMIM) entries, genomic coordinates, gene symbols, or Entrez IDs. We also provide an integrated genome browser for users to easily access mosaic variants and their related annotations for any genomic region. By analyzing the variants collected in MosaicBase, we find that mosaic variants that directly contribute to disease phenotype show features distinct from those of variants in individuals with mild or no phenotypes, in terms of their genomic distribution, mutation signatures, and fraction of mutant cells. MosaicBase will not only assist clinicians in genetic counseling and diagnosis but also provide a useful resource to understand the genomic baseline of postzygotic mutations in the general human population. MosaicBase is publicly available at http://mosaicbase.com/ or http://49.4.21.8:8000.

Ginseng is a perennial herb with a long growth cycle and is known to easily accumulate pesticides during its growth process, seriously threatening people's health. Therefore, to ensure safe consumption, it is necessary to detect and monitor pesticide residues in ginseng. In this study, a novel analysis method was established for simultaneous determination of 31 pesticides in ginseng by high-performance liquid chromatography-mass spectrometry. Ginseng samples were extracted using acetonitrile, cleaned up by primary secondary amine (PSA) solid-phase extraction column eluted with acetonitrile-toluene, and then detected in multiple reaction mode (MRM). The calibration curves of target compounds were linear in the range of 0.005–1.0 mg/L, with correlation coefficients greater than 0.9921. The limits of detection of all the pesticides in ginseng were between 4.4×10−5 and 1.6 × 10−2 mg/kg. For fresh ginseng, the average recoveries ranged from 72.1 to 111.6%, and the relative standard deviations were 1.3–12.2%. For dry ginseng, the average recoveries were 74.3–108.3%, and the relative standard deviations were 0.9–14.9%. The residual concentrations of some pesticides in real samples were greater than the maximum residue limit (MRL) for European Union (EU). The method established here is rapid and simple with high sensitivity and good reproducibility, which is sensitive in the residue analysis of many pesticides in ginseng.

Background and Objectives: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often lead to high mortality. Chronic obstructive pulmonary disease and asthma physiology score (CAPS) is a simple clinical severity score. The aim of this study was to explore whether CAPS could be an effective predictor for in-hospital and 1-year mortality in AECOPD patients. Methods. We used CAPS to grade all patients and record their clinical characteristics. The receiver operator characteristic (ROC) curve was used to determine the cut-off of CAPS that discriminated survivors and non-survivors. Univariate and multivariate logistic regression analyses and Cox regression analyses were used to identify the risk factors for in-hospital and 1-year mortality, respectively. Results. 240 patients were enrolled in our study; 18 patients died during hospitalization and 29 patients died during the 1-year follow-up. Compared with in-hospital survivors, those who died were older (80.83 ± 6.06 vs. 76.94 ± 8.30 years old, P = 0.019) and had a higher percentage of congestive heart failure (61.1% vs. 14.4%, P

In this study, the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method, combined with high-performance liquid chromatography–tandem mass spectrometry, was chosen for detecting pydiflumetofen residues in soybean plants, soybeans and soil, and assessing the risk of short- and long-term dietary intake. Pydiflumetofen concentrations ranging from 0.001–0.5 mg/L exhibited good linearity (r > 0.997). At varying doses, the average pydiflumetofen recovery rates and relative standard deviations among soybean plants, soybeans, and soil ranged from 83.9 ± 1.1% to 99.5 ± 3.3% and from 0.77 to 7.77%, respectively. The sensitivity, accuracy, and precision of the chosen methodology met the requirements of pesticide residue analysis. The results of the degradation dynamics test showed that the half-life of pydiflumetofen (t1/2) in soybean plants and in soil were 3.6 to 5.7 and from 7.9 to 25.7 d, respectively. Assessment of the concentration of pydiflumetofen residues in soybeans revealed acute and chronic dietary exposure risks of 0.06 and 7.54%, respectively. As these values are very low, pydiflumetofen residues in soybeans present an acceptable risk to public health. The results of this study will help to guide the practical application of pydiflumetofen and minimize the environmental risks associated with its use.

Although the effects of N deposition on forest plants have been widely reported, few studies have focused on rare and endangered fern species (REFs). Information is also lacking on the effects of micro-environments on REFs. We investigated the effects of N addition (canopy and understory N addition, CAN, and UAN) and micro-environments (soil and canopy conditions) on the functional traits (growth, defense, and reproduction; 19 traits in total) of two REFs—Alsophila podophylla and Cibotium baromet—in a subtropical forest in South China. We found that, compared to controls, CAN or UAN decreased the growth traits (e.g., plant height, H) of C. baromet, increased its defense traits (e.g., leaf organic acid concentrations, OA), delayed its reproductive event (all-spore release date), and prolonged its reproductive duration. In contrast, A. podophylla showed increased growth traits (e.g., H), decreased defense traits (e.g., OA), and advanced reproductive events (e.g., the all-spore emergence date) under CAN or UAN. Meanwhile, the negative effects on the C. baromet growth traits and A. podophylla defense traits were stronger for CAN than for UAN. In addition, the soil chemical properties always explained more of the variations in the growth and reproductive traits of the two REFs than the N addition. Our study indicates that, under simulated N deposition, C. baromet increases its investment in defense, whereas A. podophylla increases its investment in growth and reproduction; this may cause an increasing A. podophylla population and decreasing C. baromet population in subtropical forests. Our study also highlights the importance of considering micro-environments and the N-addition approach when predicting N deposition impact on subtropical forest REFs.

Mulberry extract from Fructus Mori contains an anthocyanin pigment and has been widely used as a food additive in China and other Eastern Asian countries. Only few research has been done on toxicological profiling of mulberry extract for its safety evaluation; however, the data is inconclusive. In the current study, mulberry extract of 4200, 1400, or 466 mg/kg were orally administrated to Sprague Dawley rats for 90 consecutive days followed by a recovery period of 28 days. No abnormalities were detected in body weights, food intake, ophthalmological, hematological, coagulation, clinical chemistry, and organ weights parameters. Discoloration of urine (red, purple, and brown) and feces (black), along with bedding material (purple) were observed in the 4200 mg/kg group. Further, microscopic examination revealed brown granules in the renal tubular cells for rats in 4200 and 1400 mg/kg groups. Since these changes were associated with excretory effect of the extract, the No Observed Adverse Effect Level was determined to be 4200 mg/kg, which was equivalent to the 1058.5 mg/kg of anthocyanin.

Objective: The purpose of this study was to investigate the effect of dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, on relieving cardiac hypertrophy and its potential molecular mechanism.Methods: Cardiac hypertrophy induced by abdominal aortic constriction (AAC) in mice, dapagliflozin were administered in the drinking water at a dose of 25 mg/kg/d for 12 weeks was observed. Echocardiography was used to detect the changes of cardiac function, including LVEF, LVFS, LVEDd, LVEDs, HR and LV mass. Histological morphological changes were evaluated by Masson trichrome staining and wheat germ agglutinin (WGA) staining. The enrichment of differential genes and signal pathways after treatment was analyzed by gene microarray cardiomyocyte hypertrophy was induced by AngII (2 μM) and the protective effect of dapagliflozin (1 μM) was observed in vitro. The morphological changes of myocardial cells were detected by cTnI immunofluorescence staining. ELISA and qRT-PCR assays were performed to detect the expressions levels of cardiac hypertrophy related molecules.Results: After 12 weeks of treatment, DAPA significantly ameliorated cardiac function and inhibited cardiac hypertrophy in AAC-induced mice. In vitro, DAPA significantly inhibited abnormal hypertrophy in AngII-induced cardiacmyocytes. Both in vivo and in vitro experiments have confirmed that DAPA could mediate the Plin5/PPARα signaling axis to play a protective role in inhibiting cardiac hypertrophy.Conclusion: Dapagliflozin activated the Plin5/PPARα signaling axis and exerts a protective effect against cardiac hypertrophy.

Butralin can effectively mitigate the spreading of weeds in ginseng fields, however, the dissipation and residues of butralin in ginseng have not been investigated. In this study, we established a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method to determine the butralin residue and its dissipation in ginseng and its dietary intake risk. The mean recoveries of butralin in ginseng (fresh, dried, plants, and soil) ranged from 93.1–107.5% with relative standard deviations of 0.7–6.4%. The half-lives of butralin in ginseng plant and soil were 10.81–18.91 days, and its final residues in ginseng, dried gingeng, gingeng plant, and soil were −4, which suggests that the consumption of butralin-treated ginseng during the harvest period does not affect human health.

Abstract The application of endophytic bacteria, particularly members of the genus Bacillus, offers a promising strategy for the biocontrol of plant fungal diseases, owing to their sustainability and ecological safety. Although multiple secondary metabolites that demonstrate antifungal capacity have been identified in diverse endophytic bacteria, the regulatory mechanisms of their biosynthesis remain largely unknown. To elucidate this, we sequenced the entire genome of Bacillus amyloliquefaciens GKT04, a strain isolated from banana root, which showed high inhibitory activity against Fusarium oxysporum f. sp. cubense race 4 (FOC4). The GKT04 genome consists of a circular chromosome and a circular plasmid, which harbors 4,087 protein‐coding genes and 113 RNA genes. Eight gene clusters that could potentially encode antifungal components were identified. We further applied RNA‐Seq analysis to survey genome‐wide changes in the gene expression of strain GKT04 during its inhibition of FOC4. In total, 575 upregulated and 242 downregulated genes enriched in several amino acid and carbohydrate metabolism pathways were identified. Specifically, gene clusters associated with difficidin, bacillibactin, and bacilysin were significantly upregulated, and their gene regulatory networks were constructed. Our work thereby provides insights into the genomic features and gene expression patterns of this B. amyloliquefaciens strain, which presents an excellent potential for the biocontrol of Fusarium wilt.

The unprecedented use of English as a means of international and intercultural communication around the world has made it increasingly unrealistic and inappropriate to hold to the native speaker norms. This paper examines preservice teachers’ perceptions of teaching English as an International Language (EIL), employing qualitative methods. The participants were 31 teacher candidates enrolled in an undergraduate course “Teaching English as a Second Language” in the teacher education program of a public university in a Southwestern State of the U.S. The data sources included online postings, interview transcripts, and synthesis papers. This study revealed that although the participants were all aware of the heterogeneity of the English language and were willing to promote multilingualism, the majority of them still clung to the notion that “Standard” English is the only variety of English that should be taught in the classroom. This paper maintains that in order to raise classroom teachers’ awareness of teaching EIL, teacher educators should demolish American or British English as the orthodox and establish a new pedagogic model that de-emphasizes the native speaker norms and embraces all varieties of the English language.

Abstract Background Autism prevalence in the West is approximately 1% of school age children. Autism prevalence in China has been reported to be lower than in the West. This is likely due to at least two reasons: (1) most studies in China only included the special school population, overlooking the mainstream school population; and (2) most studies in China have not used contemporary screening and diagnostic methods. To address this, we tested total autism prevalence (mainstream and special schools) in Jilin City, and mainstream school autism prevalence in Jiamusi and Shenzhen cities. Methods The study included a three-step process: (1) screening; (2) clinical assessment of ‘screen positives’ plus controls; and (3) research diagnostic assessment of those meeting clinical threshold for concerns at step 2. Prevalence estimates per 10,000 children aged 6–10 years old were weighted for study design using diagnostic criteria applied at the research assessment stage. Results In Jilin City, 77 cases of autism were identified from a total population of 7258, equating to a prevalence of 108 per 10,000 (95% confidence interval (CI) 89, 130). In Shenzhen City: 21,420 children were screened and 35 cases of autism were identified, resulting in a mainstream prevalence of 42 per 10,000 (95% CI 20–89). In Jiamusi City, 16,358 children were screened, with 10 autism cases being identified, with a mainstream prevalence of 19 per 10,000 (95% CI 10–38). Conclusions Results from Jilin City, where both mainstream and special school data were available, revealed a similar prevalence of autism in China to the West, at around 1%. Results from Shenzhen and Jiamusi cities, where only mainstream data were available, prevalence is also in line with Western estimates. In all three cities, new cases of autism were identified by the study in mainstream schools, reflecting current under-diagnosis. Non-significant variation across different cities is seen indicating the need to explore potential variation of autism across diverse Chinese regions with large sample sizes to achieve a fully robust national picture.

Photon-counting analysis plays a key role in many areas, such as biology, chemistry, and medicine. In this paper, we present an integrated time-correlated single photon counting (TCSPC) lifetime analytical system with a complete signal path-from fluorophore excitation, emission detection, to lifetime extraction. The time-to-digital module of the proposed TCSPC system achieves a root-mean-square differential non-linearity of 4% of the least significant bit and a full width at half maximum temporal resolution from 121 to 145 ps within the 500-ns full-scale range. To evaluate the lifetime extraction and detection limit of the proposed TCSPC system, a wide variety of samples, such as fluorescein in water, coumarin 6 in dimethyl sulfoxide, and rhodamine 6G in water, each prepared in 14 concentrations from 0.5 nM (nanomolar, 10-9 mol/L) to 25 μM (micromolar, 10-6 mol/L), are tested. With the optimized hardware and firmware design, the proposed TCSPC system can accurately extract the fluorescence lifetime of fluorescein, coumarin 6, and rhodamine 6G down to the concentration of 1, 1, and 2.5 nM, respectively, significantly outperforming similar fluorescence lifetime analysis systems.

Time-resolved fluorescence is a widely adopted technique for DNA detection due to its high sensitivity and selectivity. However, due to stringent requirements on optics and electronics, instrumentation with time-resolved capability is bulky and expensive, prohibiting their use in portable and point-of-care applications. In this work, a fully-integrated DNA biosensor based on liquid-core waveguide (LCW) optics for fluorescence lifetime analysis is presented. The DNA biosensor encompasses all-custom bioassay, optics and electronics into a microsystem, delivering a near sample-to-answer level of integration. Lifetime, rather than intensity, is exploited as the analytical signal from the V-carbazole probe for the first time. Excitation propagation within the LCW is investigated both analytically and in simulations to achieve high excitation rejection and low temporal dispersion, enabling the proposed LCW-based system with much smaller instrumentation size to deliver comparable lifetime measurement accuracy to traditional systems. Detection of DNA down to 15 base pairs at a low detection limit of 1.38 nM demonstrates the high applicability of the proposed biosensor for compact, application-specific, and low-cost diagnostics devices.

A new route to obtain a layer of micro-nanostructured Fe3O4 using hydrothermal method has been reported. The prepared dual-scale film, after a two-stage heat treatment and surface modification with dopamine and octadecylamine, shows a contact angle of 158.3° and sliding angle of 3.3°. The corrosion current density and the impedance of the superhydrophobic surface protected steel sample were, respectively, one order of magnitude lower and 32 times higher than that of the bare N80 steel in a 5 wt% NaCl aqueous solution. The superhydrophobic Fe3O4 film demonstrated excellent self-cleaning performance and was able to maintain its anti-wetting performance after water jetting test. Our work finds that annealing in N2 and then in O2 plays a significant role in fabricating the superhydrophobic Fe3O4 film for corrosion protection as this treatment is able to realize the desirable micro-nanostructured oxide structure. Keywords: Superhydrophobic, Fe3O4, Corrosion protection, Annealing, N80 steel

The incidence rate of thyroid carcinoma ranks ninth among human malignancies, and it accounts for the most frequent malignancy in endocrine-related tumors. This study aimed to investigate the role of long noncoding RNA (lncRNA) ZFAS1 in the metastasis of papillary thyroid carcinoma (PTC) and the potential molecular mechanisms. Both ZFAS1 and MMP3 were highly expressed in thyroid carcinoma and PTC cell, as measured by the q-PCR and TCGA database. In addition, ZFAS1 induced TPC-1 metastasis through inducing the epithelial–mesenchymal transition (EMT) process. Besides, ZFAS1 knockdown by siRNA induced miR-373-3p expression and reduced MMP3 expression, as quantified by q-PCR and Western blotting. According to the luciferase assay, both ZFAS1 and MMP3 were classified as the direct targets of miR-373-3p. However, MMP3 itself did not affect ZFAS1. Using the online prediction tool, CREB3 was predicted as the transcription factor (TF) of ZFAS1 that contained two binding sites on its promoter region, and CREB3 was positively correlated with ZFAS1 in thyroid carcinoma cohorts. Results from the dual-luciferase assay and ChIP-qPCR indicated that both the two binding sites were essential for the transcription of ZFAS1. In conclusion, CREB3 activated lncRNA ZFAS1 at the transcriptional level to promote PTC metastasis by modulating miR-373-3p/MMP3.

Aberrant activation of angiotensin II (Ang II) accelerates hypertensive heart failure (HF); this has drawn worldwide attention. The complex Ang II/transforming growth factor (TGF)-β1 networking consists of central mechanisms underlying pro-fibrotic effects; however, this networking still remains unclear. Cellular communication network 5 (CCN5), known as secreted matricellular protein, mediates anti-fibrotic activity by inhibiting fibroblast-to-myofibroblast transition and the TGF-β1 signaling pathway. We hypothesized that endogenous CCN5 plays an essential role in TGF-β1/Ang II networking-induced cardiac fibrosis (CF), which accelerates the development of hypertensive HF. This study aimed to investigate the potential role of CCN5 in TGF-β1/Ang II networking-induced CF. Our clinical retrospective study demonstrated that serum CCN5 decreased in hypertensive patients, but significantly increased in hypertensive patients taking oral angiotensin-converting enzyme inhibitor (ACEI). A negative association was observed between CCN5 and Ang II in grade 2and 3 hypertensive patients receiving ACEI treatment. We further created an experimental model of high Ang II-induced hypertensive HF. CCN5 was downregulated in the spontaneously hypertensive rats (SHRs) and increased via the inhibition of Ang II production by ACEI. This CCN5 downregulation may activate the TGF-β1 signaling pathway, which promotes direct deposition of the extracellular matrix (ECM) and fibroblast-to-myofibroblast transition via activated Smad-3. Double immunofluorescence staining of CCN5 and cell markers of cardiac tissue cell types suggested that CCN5 was mainly expressed in the cardiac fibroblasts. Isolated cardiac fibroblasts were exposed to Ang II and transfected with small interfering RNA targeting CCN5. The expression of TGF-β1 together with Col Ia and Col IIIa was further promoted, and alpha-smooth muscle actin (α-SMA) was strongly expressed in the cardiac fibroblasts stimulated with Ang II and siRNA. In our study, we confirmed the anti-fibrotic ability of endogenous CCN5 in high Ang II-induced hypertensive HF. Elevated Ang II levels may decrease CCN5 expression, which subsequently activates TGF-β1 and finally promotes the direct deposition of the ECM and fibroblast-to-myofibroblast transition via Smad-3 activation. CCN5 may serve as a potential biomarker for estimating CF in hypertensive patients. A novel therapeutic target should be developed for stimulating endogenous CCN5 production.

BackgroundMetabolic remodeling plays a vital role in the development of heart failure. The trimetazidine can optimize fatty acid and glucose oxidation via inhibition of long-chain 3-ketoacyl CoA thiolase in the heart. So, trimetazidine commonly used in cardiovascular therapy as a myocardial metabolic drug. This study was conducted to assess the effects and mechanisms of trimetazidine on ketone body metabolism in heart failure rats.MethodsA rat model of heart failure was established by continuous subcutaneous injection of isoproterenol in 10 mg/kg/d. We examined body weight, heart weight index, and tested B-type natriuretic peptide by kit. We detected the structure and function of the heart. Hematoxylin-eosin staining and Masson’s trichrome staining was performed to assess myocardial tissue morphology. To evaluate apoptosis, we used Tunel staining. Metabolic substrate contents of glucose, free fatty acid, ketone bodies, lactic acid, and pyruvate and ATP levels in myocardial tissues were measured with the corresponding kit. We detected the levels of protein expressions related to myocardial substrate uptake and utilization by Western blot.ResultsTrimetazidine remarkably reduced the heart weight index and B-type natriuretic peptide levels. Besides, trimetazidine increased the level of blood pressure and decreased heart rate. Moreover, trimetazidine inhibited decreases in left ventricular ejection fraction and left ventricular fractional shortening. Further, trimetazidine decreased the levels of collagen volume fraction and promoted ATP production in myocardial tissues. Trimetazidine also reduced the levels of free fatty acid, ketone bodies, lactic acid, and increased glucose and pyruvate levels in myocardial tissues. Furthermore, trimetazidine markedly inhibited apoptosis. More importantly, the protein expression levels related to myocardial substrate uptake and utilization increased dramatically in the trimetazidine group. In particular, the protein expressions related to ketone body utilization were prominent.ConclusionsTrimetazidine could attenuate metabolic remodeling and improve cardiac function in heart failure rats. The potential mechanism for the cardioprotective effect of trimetazidine may be highly associated with its regulation of adenosine monophosphate-activated protein kinase, and peroxisome proliferator activated receptor α expressions. Along with the regulation, myocardial substrate utilization was improved, especially the utilization of ketone bodies.

Pancreatic cancer is one of the most severe types of tumors, with a 5-year survival rate of less than 7%. The prognosis and treatment of pancreatic cancer are largely limited by the extent of tumor invasion and the presence of lymph node and distant metastases. Therefore, exploring the biological behavior of pancreatic cancer cells (PCCs) is extremely important for the understanding, diagnosis, and treatment of pancreatic cancer. Current studies have shown that pancreatic stellate cells (PSCs) regulate the biological behavior of PCCs, such as their proliferation, apoptosis, invasion, and migration, by remodeling the extracellular matrix. Though Hic-5 is an important gene in PSCs, no study has investigated the regulation of PCCs by Hic-5. Here, we demonstrate that Hic-5 expression is upregulated in pancreatic cancer and that siRNA transfection can effectively inhibit Hic-5 expression. Compared to the control group, Hic-5 inhibition significantly reduced proliferation, increased apoptosis, and reduced invasion and migration of PCCs. Moreover, the inhibition of Hic-5 expression simultaneously reduced matrix metalloproteinase-9 (MMP-9) expression. Statistical analysis revealed that Hic-5 expression was higher among the pancreatic cancer group than among the normal group and was negatively correlated with postoperative survival time among patients with pancreatic cancer. These results have important clinical significance for further exploring the molecular mechanism involved in Hic-5-mediated invasion and metastasis of pancreatic cancer and ameliorating the prognosis of patients with pancreatic cancer.

Abstract Characterization of the rupture risk factors for small intracranial aneurysms (SIAs, ≤5 mm) is clinically valuable. The present study aims to identify image-based morphological parameters and anatomical locations associated with the rupture status of SIAs. Two hundred and sixty-three patients with single SIAs (128 ruptured, 135 unruptured) were included, and six morphological parameters, including size, aspect ratio (AR), size ratio (SR), height–width ratio (H/W), flow angle (FA) and aneurysm width–parent artery diameter ratio, and the aneurysm locations were evaluated using three-dimensional geometry, and were used to identify a correlation with aneurysm rupture. Statistically significant differences were observed between ruptured and unruptured groups for AR, SR, H/W, FA, and aneurysm locations, from univariate analyses. Logistic regression analysis further revealed that AR (p = 0.034), SR (p = 0.004), H/W (p = 0.003), and FA (p