Transcription factor LBD16 targets cell wall modification/ion transport genes in peach lateral root formation.

LATERAL ORGAN BOUNDARIES DOMAIN/ASYMMETRIC LEAVES2-LIKEs (LBDs/ASLs) are plant-specific transcription factors that function downstream of auxin-regulated lateral root (LR) formation. Our previous research found that PpLBD16 positively regulates peach (Prunus persica) LR formation. However, the downstream regulatory network and target genes of PpLBD16 are still largely unknown. Here, we constructed a PpLBD16 homologous overexpression line and a PpLBD16 silenced line. We found that overexpressing PpLBD16 promoted peach root initiation, while silencing PpLBD16 inhibited peach root formation. Through RNA sequencing (RNA-seq) analysis of roots from PpLBD16 overexpression and silenced lines, we discovered that genes positively regulated by PpLBD16 were closely related to cell wall synthesis and degradation, ion/substance transport, and ion binding and homeostasis. To further detect the binding motifs and potential target genes of PpLBD16, we performed DNA-affinity purification sequencing (DAP-seq) analysis in vitro. PpLBD16 preferentially bound to CCNGAAANNNNGG (MEME-1), [C/T]TTCT[C/T][T/C] (MEME-2), and GCGGCGG (ABR1) motifs. By combined analysis of RNA-seq and DAP-seq data, we screened candidate target genes for PpLBD16. We demonstrated that PpLBD16 bound and activated the cell wall modification-related genes EXPANSIN-B2 (PpEXPB2) and SUBTILISIN-LIKE PROTEASE 1.7 (PpSBT1.7), the ion transport-related gene CYCLIC NUCLEOTIDE-GATED ION CHANNEL 1 (PpCNGC1) and the polyphenol oxidase (PPO)-encoding gene PpPPO, thereby controlling peach root organogenesis and promoting LR formation. Moreover, our results displayed that PpLBD16 and its target genes are involved in peach LR primordia development. Overall, this work reveals the downstream regulatory network and target genes of PpLBD16, providing insights into the molecular network of LBD16-mediated LR development.

METTL3-mediated lncRNA HNF1A-AS1/HNF4A-AS1 m6A modification regulates CYP expression.

Interindividual variations in the expression and activity of cytochrome P450 enzymes (CYPs) led to lower therapeutic efficacy or adverse drug events. We previously demonstrated that CYPs are regulated by the long non-coding RNAs (lncRNAs) HNF1A-AS1 and HNF4A-AS1 via transcription factors (TFs) including hepatocyte nuclear factor 1a (HNF1A), hepatocyte nuclear factor 4a (HNF4A), and pregnane X receptor (PXR). However, the upstream mechanisms regulating HNF1A-AS1 and HNF4A-AS1 are poorly understood. N6-methyladenosine (m6A) is a prevalent epi transcriptomic modification in mammalian RNA. Therefore, the aim of this study was to investigate whether m6A modification regulates the expression of HNF1A-AS1 and HNF4A-AS1 and affects CYP expression in HepG2 and Huh7 cells. The methyltransferase-like 3 (METTL3) inhibitor, STM2457, significantly suppressed the expression of HNF1A-AS1 and induced HNF4A-AS1 expression. Consistent with this, a loss-of-function assay of METTL3 in the cell lines resulted in the down-regulation of HNF1A-AS1 and its downstream HNF1A, PXR, and CYPs at the RNA level, as well as the down-regulation of some CYPs proteins, and up-regulation of HNF4A-AS1. The results of gain-of-function experiments showed the opposite trend. Mechanistically, subsequent RNA stability experiments confirmed that METTL3 affected the stability of both lncRNAs, but in opposite ways; that is, METTL3 reduced HNF1A-AS1 stability and increased HNF4A-AS1 stability. Rescue experiments confirmed that the regulation of METTL3 on TFs and CYPs may require the involvement of these two lncRNAs. Altogether, our study demonstrates that METTL3 is involved in TFs-mediated CYP expression by affecting HNF1A-AS1/HNF4A-AS1 stability. Significance Statement While the impact of lncRNAs (HNF1A-AS1 and HNF4A-AS1) on the downstream TF and CYP expression is well studied, the upstream regulation of these two lncRNAs by METTL3 remains unexplored. This study systematically investigated the regulation by METTL3 on the expression of lncRNAs (HNF1A-AS1 and HNF4A-AS1) and their downstream TFs (HNF1A, HNF4A, and PXR) and CYPs in HepG2 and Huh7 cells, revealing that METTL3 is involved in the regulation of lncRNA-TF-CYP expression by affecting the stability of HNF1A-AS1 and HNF4A-AS1.

GHS-R1a activity suppresses synaptic function of primary cultured hippocampal neurons.

Ghrelin is an orexigenic gastric hormone that promotes feeding behaviors and regulates energy homeostasis in both humans and rodents. Studies have reported intriguing yet conflicting roles that ghrelin and its receptor growth hormone secretagogue receptor 1a (GHS-R1a) play in regulating multiple brain functions, such as learning and memory; however, the underlying mechanism is largely unknown. In this study, we investigated the effect of ghrelin incubation and virus-mediated GHS-R1a overexpression on synaptic functions of primary cultured hippocampal neurons. Our results demonstrated that ghrelin pre-treatment for 24 h, with a concentration of either 4 nM or 200 nM, suppressed the frequency of miniature excitatory postsynaptic currents (mEPSCs), the frequency and the amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Similarly, GHS-R1a overexpression inhibited both the frequency and the amplitude of mEPSCs, and mIPSCs frequency. Moreover, our in vitro Ca2+-image study with Rhod-3AM reveals that ghrelin pre-treatment for either 3 h or 24 h suppressed glutamate-induced elevation of cytoplasmic [Ca2+]. Our findings thus suggest that GHS-R1a signaling inhibits synaptic function of hippocampal neurons, which may contribute to the blocking effect of ghrelin on memory formation.

Predictors for adverse events during cardiac lead extraction - Experience from a large single centre.

BACKGROUND: As the use of cardiac implantable electronic devices (CIED) has increased in recent years, the need for transvenous lead extraction (TLE) has also steadily increased. However, the TLE procedure could lead to serious complications and even death. Clinical decision-making tools are necessary for predicting these adverse events, but the appropriate tools have not yet been developed. OBJECTIVE: To explore the possible predictors and develop a clinical model to predict TLE related adverse events. METHODS: All the patients who were admitted to our cardiac center for TLE from January 2014 to January 2021 were included in this study. The patient information, device baseline characteristics, procedure-related information, complications and outcomes were recorded. Independent predictors of TLE related adverse events were identified by univariate, LASSO and multivariate analysis. A nomogram for predicting these adverse events was developed based on these independent predictors. Calibration and decision curve analysis were conducted to evaluate the nomogram. RESULTS: One thousand and one hundred patients were included in this study, 778 (70.7%) were male and the median age was 68 years old. A total of 2,208 leads were extracted and 2.01±0.74 leads were extracted per procedure. Fifty-five patients (5%) developed adverse events including minor complications (2.4%), major complications (2.3%) and death (0.27%). Seven independent predictors for TLE related adverse events were identified and selected to establish the nomogram including BMI, female gender, hypoalbuminemia, number of extracted leads>3, longest dwell time of the extracted leads and manual traction. The area under the receiver operating characteristic (ROC) curve (AUC) for the prediction model was 0.774. Calibration curve and decision curve analysis showed that the nomogram had good prediction performance. CONCLUSION: TLE related adverse events are some of the key issues that concern clinicians. We have identified seven independent factors and established a predictive model that may help clinicians identify at-risk patients and create better plans for lead extraction.

The Covid-19 outbreak, corporate financial distress and earnings management.

This study explores the association between the Covid-19 outbreak, corporate financial distress and earnings management practices in China. We investigate whether firms took advantage of the downturn in economic conditions during the pandemic to adjust their earnings using different earnings management techniques. Utilising a sample of 1832 listed firms and underlying theoretical frameworks (i.e., positive accounting and signalling theory), we find that firms were more inclined to manage earnings during the pandemic period. They favoured using the accrual-based rather than the real activity-based earnings management technique. We also find that firms engaged more in income-increasing practices in the shadow of the outbreak. In addition, our results further demonstrate that financially distressed firms were involved in earnings management, particularly accrual-based earnings management. However, compared to privately-owned firms, state-owned enterprises seem to be involved less in earnings management during the Covid-19 pandemic. Findings from this study raise some concerns for policymakers about the credibility of financial reporting information during Covid-19.

Dynamic Monitoring of Nutrition Inputs and Fertility Evaluation during a Decade in the Main Peach-Producing Areas of Shandong Province, China.

The main peach-producing area in Shandong is an important peach fruit-producing area in China. Understanding the nutritional properties of the soil in peach orchards helps us to understand the evolution of soil properties and adjust management methods in a timely manner. This study focuses on 52 peach orchards in the main peach-producing area in Shandong as the research object. The spatiotemporal changes in soil traits and their influential factors were studied in depth, and the changes in soil fertility were effectively evaluated. The results showed that the input of nitrogen, phosphorus and potassium from organic fertilizer in 2021 was significantly higher than that in 2011, while the input of fertilizer in 2011 was significantly higher than that in 2021. Compared with traditional parks, both organic fertilizer inputs and chemical fertilizer inputs in demonstration parks showed a significant downwards trend. There was no significant change in pH values between 2011 and 2021. In 2021, the soil organic matter (SOM) contents of the 0-20 cm and 20-40 cm layers were 24.17 g·kg-1 and 23.38 g·kg-1, respectively, an increase of 29.3% and 78.47% over the values measured in 2011. Compared with 2011, the content of soil alkaloid nitrogen (AN) decreased significantly in 2021, and the contents of available phosphorus (AP) and available potassium (AK) in the soil increased significantly. According to the calculation results of the comprehensive fertility index (IFI) value, we found that in 2021, compared with 2011, the quality of soil fertility improved, most of which was at the medium and high levels. The research results show that the fertilizer-saving and synergistic approach in peach orchards in China significantly improved the soil nutrition. In the future, research on suitable comprehensive technologies should be strengthened in the management of peach orchards.

Lung Microbiota Signature and Corticosteroid Responses in Pneumonia-Associated Acute Respiratory Distress Syndrome in Hematological Patients.

OBJECTIVE: In this study, we aim to classify hematological patients with the pneumonia-associated acute respiratory syndrome (ARDS) into different groups that were characterized by distinct early responsiveness to corticosteroids, describe the microbiota signatures of the non-responders and responders, and compare the prognosis of the two groups. METHODS: Hematological patients with ARDS were included and treated with mechanical ventilation and corticosteroid. According to the early improvement to the corticosteroid therapy, patients were classified as non-responders and responders. The lung microbiota signatures and the outcomes of the non-responders and responders were compared. RESULTS: Fifty patients were included in this study. Twenty-eight patients were classed as non-responders and 22 as responders. Compared to the non-responders, responders had higher serum levels of IL-6, IL-8, TNF-α and CRP, their lung microbiota was with lower alpha diversity and enriched with virus species. The responders had an overall higher ventilator free days than the non-responders [4 (0-6) vs 6 (0-10), p=0.034], for survivors the difference was more significant [5 (3-6) vs 8 (3-10), p=0.012]. Survival analysis showed that there was no difference in survival rate between the two groups over time (Log-rank p=0.073). When non-responders were stratified into subgroups of patients with infection or co-infection, those non-responders with co-infection had significantly lower survival rate than other patients (Log-rank p= 0.028). CONCLUSION: For hematological patients with pneumonia-associated ARDS, the responders of corticosteroids had higher ventilator free days at day 28 than the non-responders. The microbiota signatures were distinct in the two groups. The non-responders with coinfections had the lowest survival rate when compared to the non-responders with no coinfections and the responders.

Risk factors of prolonged ventilation after thymectomy in thymoma myasthenia gravis patients.

BACKGROUND: To explore the risk factors for prolonged ventilation after thymectomy in patients with thymoma associated with myasthenia gravis (TAMG). METHODS: We reviewed the records of 112 patients with TAMG after thymectomy between January 2010 and December 2019 in Peking University People's Hospital. Demographic, pathological, preoperative data and the Anesthesia, surgery details were assessed with multivariable logistic regression analysis to predict the risk of prolonged ventilation after thymectomy. A nomogram to predict the probability of post-thymectomy ventilation was constructed with R software. Discrimination and calibration were employed to evaluate the performance of the nomogram. RESULTS: By multivariate analysis, male, low vital capacity (VC), Osserman classification (IIb, III, IV), total intravenous anesthesia, and long operation time were identified as the risk factors and entered into the nomogram. The nomogram showed a robust discrimination, with an area under the receiver operating characteristic curve (AUC) of 0. 835 (95% confidence interval [CI], 0.757-0.913). The calibration plot indicated that the nomogram-predicted probabilities compared very well with the actual probabilities (Hosmer-Lemeshow test: P = 0.921). CONCLUSION: The nomogram is a valuable predictive tool for prolonged ventilation after thymectomy in patients with TAMG.

Application of Bag-Controlled Release Fertilizer Facilitated New Root Formation, Delayed Leaf, and Root Senescence in Peach Trees and Improved Nitrogen Utilization Efficiency.

It is very important to promote root growth and delay root and leaf senescence, to improve nitrogen absorption and utilization efficiency, and to improve the storage nutrition level of the tree, so as to improve the fruit quality and yield of peach. In this experiment, we compared and analyzed the effects of traditional fertilization and bag-controlled release fertilizer (BCRF) on the growth of shoots and roots, senescence of leaves and roots, and fruit yield and quality. Moreover, the impacts of BCRF on ammonia volatilization, nitrogen utilization rate, fine root turnover, and plant storage nutrients were also investigated. Compared with conventional fertilizer use, the application of BCRF significantly promoted the shoot growth of young peach trees. Additionally, BCRF delayed leaf senescence and increased root activity in autumn. This increased the storage nutrients of the peach tree. Compared with traditional fertilizer, ammonia volatilization reduced to 54.36% under BCRF application situation. BCRF also promoted the occurrence of fine roots and decreased the annual turnover rate. A 15N tracer test showed that, compared with traditional fertilizer, BCRF nitrogen utilization efficiency increased by 37.73% in peach trees under BCRF treatment significantly. The results from 3 consecutive years showed that the application of BCRF increased the yield of individual plants by 21.35% on average compared to the yield from plants receiving equal amounts of fertilizer applied by spreading (FSA). Thus, BCRF can promote the occurrence of fine roots and decrease the root annual turnover rate in peach trees, and it also improves the utilization efficiency of fertilizer, reduces ammonia volatilization, delays leaf senescence, and enhances storage nutrition, fruit yield, and fruit quality in peach trees.

Regulation of growth in peach roots by exogenous hydrogen sulfide based on RNA-Seq.

Hydrogen sulfide (H2S) has been shown to regulate many physiological processes of plants. In this study, we observed that 0.2 mM sodium hydrosulfide (NaHS), a donor of H2S, can regulate the root architecture of peach seedlings, increasing the number of lateral roots by 40.63%. To investigate the specific mechanisms by which H2S regulates root growth in peach, we used RNA sequencing and heterologous expression technology. Our results showed that exogenous H2S led to a 44.50% increase in the concentration of endogenous auxin. Analyses of differentially expressed genes (DEGs) revealed that 963 and 1113 genes responded to H2S on days one and five of treatment, respectively. Among the DEGs, 26 genes were involved in auxin biosynthesis, transport, and signal transduction. Using weighted correlation network analysis, we found that the auxin-related genes in the H2S-specific gene module were disproportionately involved in polar transport, which may play an important role in H2S-induced root growth. In addition, we observed that the expression of LATERAL ORGAN BOUNDARIES DOMAIN 16 (PpLBD16) was significantly up-regulated by exogenous application of H2S in peach. Overexpression of PpLBD16 in an Arabidopsis system yielded a 66.83% increase in the number of lateral roots. Under exposure to exogenous H2S, there was also increased expression of genes related to cell proliferation, indicating that H2S regulates the growth of peach roots. Our work represents the first comprehensive transcriptomic analysis of the effects of exogenous application of H2S on the roots of peach, and provides new insights into the mechanisms underlying H2S-induced root growth.

Experimental Study on High-Performers Quaternary Copolymer Based on Host-Guest Effect.

A quaternary polymer (HGP) was prepared by the free-radical polymerization of acrylamide, acrylic acid, maleic anhydride functionalized ß-cyclodextrin (MAH-ß-CD), and N-(3-methacrylamidopropyl)-N, N-dimethylnaphthalen-1-aminium chloride (NAP). It was found that host-guest behavior occurred most effectively at a molar rate of NAP and CD with 1:1, which exhibited better solubility than hydrophobically associative polymer. Moreover, the as-prepared polymer has superior salt tolerance, shear resistance, and viscoelasticity due to host-guest strategy. More importantly, the HGP solution simulates the distribution of formation water in the Bohai SZ1-1 oilfield has good rheological properties at 120 °C. All results show that the proposed polymer could be a competitive candidate in oilfield applications such as fracturing fluids, displacement fluids, and drilling fluids.

Risk factors of non-invasive ventilation failure in hematopoietic stem-cell transplantation patients with acute respiratory distress syndrome.

BACKGROUND: Non-invasive ventilation (NIV) was one of the first-line ventilation supports for hematopoietic stem-cell transplantation (HSCT) patients with acute respiratory distress syndrome (ARDS). Successful NIV may avoid need for intubation. However, the influence NIV failure had on patients' outcome and its risk factors were hardly known. METHODS: In this retrospective observational study, we reported risk factors and incidence of NIV failure in HSCT patients who were admitted to the Intensive Care Unit (ICU) with a diagnosis of ARDS and supported with mechanical ventilation, in a 5-year period. Patient outcomes, such as ventilator-free days, ICU-free days, and ICU mortality were also reported. RESULTS: Of all the 94 patients included, 70 patients were initially supported with NIV. NIV failure occurred in 44 (63%) patients. Male sex, elevated serum galactomannan (GM) test, (1-3)-ß-D-glucan (BG) assay, or elevated serum creatinine level were risk factors for NIV failure. When compared with the NIV success group, failure of NIV was associated with much fewer ICU-free days (22 versus 0, p < 0.001, Cohen's d = 0.62) and higher ICU mortality (9.5% versus 75.5%, p < 0.001, Pearson's r = 0.75). There was no difference in ICU-free days, ventilator-free days and ICU mortality between NIV failure and initial invasive mechanical ventilation (IMV) groups. Patients who failed in NIV support had a higher ICU mortality (75.5%) than those who succeeded (9.5%). CONCLUSION: In a small cohort of HSCT patients with mainly moderate severity of ARDS, male patients with elevated serum GM/BG test or serum creatinine level had a higher risk of NIV failure. Both NIV failure and initial IMV groups were characterized by high mortality rate and extremely low ICU-free days and ventilator-free days; failure of NIV support may further aggravate patient prognosis. The reviews of this paper are available via the supplemental material section.

Corrigendum: Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC.

[This corrects the article DOI: 10.3389/fphar.2019.01544.].

Differential serum exosome microRNA profile in a stress-induced depression rat model.

BACKGROUND: Increasing evidence has shown the important role of exosomes in the maintenance of brain function and pathogenesis of brain disease, but little is known about their association with depression. The aim of this project was to explore the miRNA profile of exosomes in the serum of rats with depression induced by chronic unpredictable mild stress (CUMS). METHODS: A rat model of depression was replicated via CUMS. Behavioral performance was observed, and serum exosomes were isolated and identified. The protein expression levels of brain-derived neurotrophic factor (BDNF), TrkB, and synaptotagmin 1 in the hippocampus, prefrontal cortex (PFC), and serum exosomes were measured. GO and KEGG enrichment analysis of differential genes was carried out using the R package clusterProfiler. RESULTS: The CUMS rats showed depression-like behaviors, together with decreased expression levels of BDNF, TrkB, and synaptotagmin 1 in the hippocampus, PFC, and serum exosomes. GO and KEGG enrichment analysis indicated that the differential expression of miRNAs might play an important role in the pathogenesis of stress-induced depression through the MAPK pathway, Wnt pathway, and mTOR pathway. LIMITATIONS: The protein expression levels of BDNF, TrkB, and synaptotagmin 1 were measured only in the hippocampus and PFC. The function of the differentially expressed miRNAs was not verified in the animal model, which should be investigated in detail in future studies. CONCLUSIONS: The miRNA profile was altered in rats with stress-induced depression, which might be considered a potential biomarker for the early diagnosis of depression.

Preparation of a Novel Fracturing Fluid System with Excellent Elasticity and Low Friction.

The quaternary polymer was synthesized by radical polymerization and characterized by 1H NMR. The tests of critical associating concentration and SEM suggest that there is a multilayered and robust network structure in the polymer solution. An excellent elasticity in the polymer solution by the first normal stress difference, viscoelasticity, and thixotropy was observed. The critical crosslinker concentration of polymer with sodium dodecyl sulfate and its interaction mechanism were investigated. According to the reaction kinetics, the supramolecular structure had the lowest activation energy, stable network structure, and greater thermal stability. Then the polymer was employed in the fracturing fluid due to its excellent elasticity using the intermolecular forces, which showed superior sand suspension capacity by dynamic sand suspension measurement. Meanwhile, a theoretical analysis was proposed as to why polymer solution has excellent suspension and drag reduction properties. Therefore, this polymer could be an alternative in many fields, especially in fracking, which is significant for the development of oil and gas resources in deep wells.

Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC.

Quercetin is a polyphenol with multiple biological activities, and results of our preliminary study showed that it could shorten the immobility time of mice in the forced swimming test and tail suspending test. The aim of this study was to investigate its effects on the behavioral performance of lipopolysaccharide (LPS)-challenged rats and explore the potential mechanism. The results showed that intragastrical administration of quercetin (40 mg/kg) could improve the bodyweight gain of LPS-challenged rats, increase the saccharin preference index in the saccharin preference test and the novel arm preference index in the Y-maze, and decrease the immobility time in the FST. However, it showed no significant effect on the performance of LPS-challenged rats in the Morris water maze and the plasma concentrations of nesfatin-1, C-reactive protein (CRP), and IL-6. Results of western blot showed that the expression levels of BDNF, Copine 6, p-TrkB, and the triggering receptors expressed on myeloid cells (TREM) 1 were decreased in both the hippocampus and the prefrontal cortex (PFC) of LPS-challenged rats, while the expression of TREM2 was increased. The protein expression of synapsin-1 was decreased in the hippocampus without significant changes in the PFC. These imbalance protein expressions could be balanced by treatment with quercetin. The results suggested that quercetin could alleviate LPS-induced depression-like behaviors and impairment of learning and memory in rats, the mechanism of which might be involved with regulating the BDNF-related imbalance expression of Copine 6 and TREM1/2 in the hippocampus and the PFC.