Impact of mechanical ventilation on clinical outcomes in ICU-admitted Alzheimer's disease patients: a retrospective cohort study.

Background: Alzheimer's disease (AD) is increasingly recognized as a pressing global public health issue, demanding urgent development of scientific AD management strategies. In recent years, the proportion of AD patients in Intensive Care Units (ICU) has been on the rise. Simultaneously, the use of mechanical ventilation (MV) is becoming more prevalent among this specific patient group. Considering the pathophysiological characteristics of AD, the application of MV in AD patients may lead to different outcomes. However, due to insufficient research data, the significant impact of MV on the prognosis of AD patients in the ICU remains unclear. Therefore, we conducted this study to comprehensively evaluate the potential influence of MV on the survival rate of AD patients in the ICU. Methods: We obtained data from the MIMIC-IV database for patients diagnosed with AD. Using propensity score matching (PSM), we paired patients who received MV treatment with those who did not receive treatment. Next, we conducted Cox regression analysis to evaluate the association between MV and in-hospital mortality, 7-day mortality, 28-day mortality, 90-day mortality, 4-year mortality, length of hospital stay, and ICU stay. Results: The data analysis involved a cohort of 641 AD patients spanning from 2008 to 2019, inclusive. Following a 1:2 propensity score matching (PSM) procedure, 300 patients were successfully paired, comprising 123 individuals who underwent MV treatment and 177 who did not. MV demonstrated an association with an elevated risk of in-hospital mortality (HR 5.782; 95% CI 2.981-11.216; p < 0.001), 7-day mortality (HR 6.353; 95% CI 3.014-13.392; p < 0.001), 28-day mortality (HR 3.210; 95% CI 1.977-5.210; p < 0.001), 90-day mortality (HR 2.334; 95% CI 1.537-3.544; p < 0.001), and 4-year mortality (HR 1.861; 95% CI 1.370-2.527; p < 0.001). Furthermore, it was associated with a prolonged length of ICU stay [3.6(2.2,5.8) vs. 2.2(1.6,3.7); p = 0.001]. In the subgroup analysis, we further confirmed the robustness of the results obtained from the overall population. Additionally, we observed a significant interaction (p-interaction <0.05) between age, admission type, aspirin use, statin use, and the use of MV. Conclusion: In patients with AD who are receiving treatment in the ICU, the use of MV has been linked to higher short-term, medium-term, and long-term mortality rates, as well as prolong ICU stays. Therefore, it is crucial to break away from conventional thinking and meticulously consider both the medical condition and personal preferences of these vulnerable patients. Personalized treatment decisions, comprehensive communication between healthcare providers and patients, formulation of comprehensive treatment plans, and a focus on collaboration between the ICU and community organizations become imperative.

Systematic review and meta-analysis: multimodal functional and anatomical neural alterations in autism spectrum disorder.

BACKGROUND: This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD). METHODS: A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software. RESULTS: A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences. CONCLUSIONS: The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD.

Generation of CRISPR-edited birch plants without DNA integration using Agrobacterium-mediated transformation technology.

CRISPR/Cas9 system has emerged as a powerful tool in genome editing; however, generation of CRISPR-edited DNA-free plants is still challenging. In this study, Betula platyphylla (birch) was used to build a method to generate CRISPR-edited plant without foreign DNA integration using Agrobacterium-mediated transformation (CPDAT method). This technique utilizes transient genetic transformation to introduce T-DNA coding gRNA and Cas9 into birch cells, and T-DNA will express to synthesize gRNA and Cas9 protein, which will form a complex to cleave the target DNA site. The genome may be mutated due to DNA repair, and these mutations will be preserved and accumulated not dependent on whether T-DNA is integrated into the genome or not. After transient transformation, birch plants were cut into explants to induce adventitious buds without antibiotic selection pressure. Each adventitious bud can be considered as an independent potentially CRISPR-edited line for mutation detection. CRISPR-edited birch plants without foreign DNA integration are further selected by screening CRISPR-edited lines without T-DNA integration. Among 65 randomly chosen independent lines, the mutation rate was 80.00% including 40.00% of lines with both alleles mutated. In addition, 5 lines out of 65 studied lines (7.69%) were CRISPR-edited birch plants without DNA integration. In conclusion, this innovative method presents a novel strategy for generating CRISPR-edited birch plants, thereby significantly enhancing the efficiency of generating common CRISPR-edited plants. These findings offer considerable potential to develop plant genome editing techniques further.

A Multimodal Meta-Analytical Evidence of Functional and Structural Brain Abnormalities Across Alzheimer's Disease Spectrum.

BACKGROUND: Numerous neuroimaging studies have reported that Alzheimer's disease (AD) spectrum have been linked to alterations in intrinsic functional activity and cortical thickness (CT) of some brain areas. However, the findings have been inconsistent and the correlation with the transcriptional profile and neurotransmitter systems remain largely unknown. METHODS: We conducted a meta-analysis to identify multimodal differences in the amplitude of low-frequency fluctuation (ALFF)/fractional ALFF (fALFF) and CT in patients with AD and preclinical AD compared to healthy controls (HCs), using the Seed-based d Mapping with Permutation of Subject Images software. Transcriptional data were retrieved from the Allen Human Brain Atlas. The atlas-based nuclear imaging-derived neurotransmitter maps were investigated by JuSpace toolbox. RESULTS: We included 26 ALFF/fALFF studies comprising 884 patients with AD and 1,020 controls, along with 52 studies comprising 2,046 patients with preclinical AD and 2,336 controls. For CT, we included 11 studies comprising 353 patients with AD and 330 controls. Overall, compared to HCs, patients with AD showed decreased ALFF/fALFF in the bilateral posterior cingulate gyrus (PCC)/precuneus and right angular gyrus, as well as increased ALFF/fALFF in the bilateral parahippocampal gyrus (PHG). Patients with peclinical AD showed decreased ALFF/fALFF in the left precuneus. Additionally, patients with AD displayed decreased CT in the bilateral PHG, left PCC, bilateral orbitofrontal cortex, sensorimotor areas and temporal lobe. Furthermore, gene sets related to brain structural and functional changes in AD and preclincal AD were enriched for G protein-coupled receptor signaling pathway, ion gated channel activity, and components of biological membrane. Functional and structural alterations in AD and preclinical AD were spatially associated with dopaminergic, serotonergic, and GABAergic neurotransmitter systems. CONCLUSIONS: The multimodal meta-analysis demonstrated that patients with AD exhibited convergent functional and structural alterations in the PCC/precuneus and PHG, as well as cortical thinning in the primary sensory and motor areas. Furthermore, patients with preclinical AD showed reduced functional activity in the precuneus. AD and preclinical AD showed genetic modulations/neurotransmitter deficits of brain functional and structural impairments. These findings may provide new insights into the pathophysiology of the AD spectrum.

Association between acetaminophen administration and clinical outcomes in patients with sepsis admitted to the ICU: a retrospective cohort study.

Background: Sepsis, affecting over 30 million people worldwide each year, is a key mortality risk factor in critically ill patients. There are significant regional discrepancies in its impact. Acetaminophen, a common over-the-counter drug, is often administered to control fever in suspected infection cases in intensive care units (ICUs). It is considered generally safe when used at therapeutic levels. Despite its widespread use, there's inconsistent research regarding its efficacy in sepsis management, which creates uncertainties for ICU doctors about its possible advantages or harm. To address this, we undertook a retrospective cohort study utilizing the MIMIC-IV database to examine the correlation between acetaminophen use and clinical outcomes in septic patients admitted to the ICU. Methods: We gathered pertinent data on sepsis patients from the MIMIC-IV database. We used propensity score matching (PSM) to pair acetaminophen-treated patients with those who were not treated. We then used Cox Proportional Hazards models to examine the relationships between acetaminophen use and factors such as in-hospital mortality, 30-day mortality, hospital stay duration, and ICU stay length. Results: The data analysis involved 22,633 sepsis patients. Post PSM, a total of 15,843 patients were matched; each patient not receiving acetaminophen treatment was paired with two patients who received it. There was a correlation between acetaminophen and a lower in-hospital mortality rate (HR 0.443; 95% CI 0.371-0.530; p < 0.001) along with 30-day mortality rate (HR 0.497; 95% CI 0.424-0.583; p < 0.001). Additionally, it correlated with a decrease in the duration of hospitalization [8.4 (5.0, 14.8) vs. 9.0 (5.1, 16.0), p < 0.001] and a shorter ICU stay [2.8 (1.5, 6.0) vs. 3.1 (1.7, 6.5); p < 0.05]. Conclusion: The use of acetaminophen may lower short-term mortality in critically ill patients with sepsis. To confirm this correlation, future research should involve multicenter randomized controlled trials.

The therapeutic effect of wine-processed Corni Fructus on chronic renal failure in rats through the interference with the LPS/IL-1-mediated inhibition of RXR function.

ETHNOPHARMACOLOGICAL RELEVANCE: Corni Fructus, derived from the fruit of Cornus officinalis Sieb. et Zucc, is a widely utilized traditional Chinese medicine (TCM) with established efficacy in the treatment of diverse chronic kidney diseases. Crude Corni Fructus (CCF) and wine-processed Corni Fructus (WCF) are the main processed forms of Corni Fructus. Generally, TCM is often used after processing (paozhi). Despite the extensive use of processed TCM, the underlying mechanisms of processing for most TCMs have been unclear so far. AIM OF THE STUDY: In this study, an integrated strategy combined renal metabolomics with proteomics was established and investigated the potential processing mechanisms of CCF or WCF on chronic renal failure (CRF) models. MATERIALS AND METHODS: Firstly, the differences in biochemical parameters and pathological histology were compared to evaluate the effects of CCF and WCF on CRF model rats. Then, the tissue differential metabolites and proteins between CCF and WCF on CRF model rats were screened based on metabolomics and proteomics technology. Concurrently, a combined approach of metabolomics and proteomics was employed to investigate the underlying mechanisms associated with these marker metabolic products and proteins. RESULTS: Compared to the MG group, there were 27 distinct metabolites and 143 different proteins observed in the CCF-treatment group, while the WCF-treatment group exhibited 24 distinct metabolites and 379 different proteins. Further, the integration interactions analysis of the protein and lipid metabolite revealed that both WCF and CCF improved tryptophan degradation and LPS/IL-1-mediated inhibition of RXR function. WCF inhibited RXR function more than CCF via the modulation of LPS/IL-1 in the CRF model. Experimental results were validated by qRT-PCR and western blotting. Notably, the gene expression amount and protein levels of FMO3 and CYP2E1 among 8 genes influenced by WCF were higher compared to CCF. CONCLUSION: The results of this study provide a theoretical basis for further study of Corni Fructus with different processing techniques in CRF. The findings also offer guidance for investigating the mechanism of action of herbal medicines in diseases employing diverse processing techniques.

Meta-analysis of cortical thickness reduction in adult schizophrenia.

BACKGROUND: Numerous neuroimaging studies using surface-based morphometry analyses have reported altered cortical thickness among patients with schizophrenia, but the results have been inconsistent. We sought to provide a whole-brain meta-analysis, which may help enhance the spatial accuracy of identification. METHODS: We conducted a meta-analysis of whole-brain studies that explored cortical thickness alteration among adult patients with schizophrenia, including first-episode patients with schizophrenia, and patients with chronic schizophrenia, compared with healthy controls by using the seed-based d mapping with permutation of subject images (SDM-PSI) software. RESULTS: A systematic literature search identified 25 studies (33 data sets) of cortical thickness, including 2008 patients with schizophrenia and 2004 healthy controls. Overall, patients with schizophrenia showed decreased cortical thickness in the right inferior frontal gyrus (IFG) and bilateral insula extending to the superior temporal gyrus (STG). Subgroup meta-analysis reported that patients with chronic schizophrenia showed decreased cortical thickness in the right insula extending to the right IFG. There was no significant cortical thickness difference between first-episode patients with schizophrenia and healthy controls. LIMITATIONS: The results of meta-regression analyses should be viewed cautiously since they were driven by a small number of studies or did not overlap with the between-group differences found in the primary analyses. CONCLUSION: The meta-analysis suggested robust cortical thickness reduction in the IFG, insula and STG among adult patients with schizophrenia, particularly in those with chronic schizophrenia. The results provide useful insights to understanding the underlying pathophysiology of schizophrenia.

Bionic Structure Inspired by Tree Frogs to Enhance Damping Performance.

Magnetic fluid shock absorbers (MFSAs) have been successfully utilized to eliminate microvibrations of flexible spacecraft structures. The method of enhancing the damping efficiency of MFSAs has always been a critical issue. To address this, we drew inspiration from the tree frog's toe pads, which exhibit strong friction due to their unique surface structure. Using 3D printing, we integrated bionic textures copied from tree frog's toe pad surfaces onto MFSAs, which is the first time to combine bionic design and MFSAs. Additionally, this is also the first time that surface textures have been applied to MFSAs. However, we also had to consider practical engineering applications and manufacturing convenience, so we modified the shape of bionic textures. To do so, we used an edge extraction algorithm for image processing and obtained recognition results. After thorough consideration, we chose hexagon as the shape of surface textures instead of bionic textures. For theoretical analysis, a magnetic field-flow field coupling dynamic model for MFSAs was built for the first time to simulate the magnetic fluid (MF) flow in one oscillation cycle. Using this model, the flow rate contours of the MF were obtained. It was observed that textures cause vortexes to form in the MF layer, which produced an additional velocity field. This increased the shear rate, ultimately leading to an increase in flow resistance. Finally, we conducted vibration reduction experiments and estimated damping characteristics of the proposed MFSAs to prove the effectiveness of both bionic texture and hexagon surface textures. Fortunately, we concluded that hexagon surface textures not only improve the damping efficiency of MFSAs but also require less MF mass.

Integrated metabolomics, network pharmacology, and molecular docking to reveal the mechanisms of Isodon excisoides against drug-induced liver injury.

Isodon excisoides (Y.Z.Sun ex C.H.Hu) H. Hara has been often used to treat liver diseases in folk medicine. However, the potential hepatoprotective mechanism of I. excisoides remains unclear. In this study, the mechanism of I. excisoides in alleviating drug-induced liver injury (DILI) was explored using a strategy combining metabolomics with network pharmacology for the first time. First, serum metabolomics was applied to identify differential metabolites and enrich metabolic pathways. The potential targets of I. excisoides for the treatment of DILI were investigated by network pharmacology. Subsequently, a comprehensive network of network pharmacology and metabolomics was established to find the key genes. Finally, molecular docking technology was used to further verify the key targets. As a result, four key genes including TYMS, IMPDH2, DHODH, and ASAH1 were identified. The proteins produced by these genes had high affinity with the corresponding diterpenoids. These results indicate that the components of I. excisoides play a liver-protective role by affecting the aforesaid key genes and key proteins. Our results offer a novel strategy for determining the pharmacological effects and potential targets of natural compounds.

Study on mechanism of hepatoprotective effect of Chrysanthemum morifolium Ramat. based on metabolomics with network analysis and network pharmacology.

Hangju (HJ), the dried flower heads of Chrysanthemum morifolium Ramat., has a significant hepatoprotective effect. However, its underlying protection mechanism against acute liver injury (ALI) has been unclear. An integrated strategy based on metabolomics with network analysis and network pharmacology was developed to explore the potential molecular mechanism of HJ on ALI protection. Firstly, differential endogenous metabolites were screened and identified by metabolomics approach and metabolic pathway analysis was performed by MetaboAnalyst. Secondly, marker metabolites were used to construct metabolite-response-enzyme-gene networks and discover hub metabolites and potential gene targets in network analysis. Thirdly, hub genes through the protein-protein interaction (PPI) network were acquired by the aid of network pharmacology. Finally, the gene targets were taken to intersect with the relevant active ingredients for validation by molecular docking. In total, 48 flavonoids were identified in HJ, which were associated with 8 potential therapeutic targets in network pharmacological analysis. Biochemistry and histopathology analysis demonstrated that HJ exerted hepatoprotective effects. 28 biomarkers were successfully identified as possible biomarkers for the prevention of ALI. The sphingolipid metabolic pathway and the glycerophospholipid metabolic pathway was considered a crucial signaling pathway by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, phosphatidylcholine and sphingomyelin were considered as hub metabolites. Twelve enzymes and 38 genes were considered as potential targets in the network analysis. Based on the combined analysis above, HJ was shown to modulate 2 key upstream targets, including PLA2G2A and PLA2G4A. Molecular docking showed that active compounds of HJ had high binding affinity with these key targets. In conclusion, the flavonoid components of HJ can inhibit PLA2 and regulate glycerophospholipid and sphingolipid metabolism pathway to delay the pathological process of ALI, which may be a potential mechanism of HJ against ALI.

An integrated strategy to explore the wine-processed mechanism of Corni Fructus on chronic renal failure based on metabolomics, network analysis and bioinformatics approaches.

OBJECTIVES: Corni Fructus is one of the most famous traditional Chinese medicines (TCMs) for the treatment of various chronic kidney diseases. Wine-processed Corni Fructus (WCF) is the main processed form of Crude Corni Fructus (CCF). In this study, potential mechanisms of action of CCF and WCF on chronic renal failure (CRF) model were developed to explore wine-processed mechanism of Corni Fructus. METHODS: An integrated strategy combining metabolomics, network analysis and bioinformatics analysis has been established to investigate the therapeutic mechanisms of WCF and CCF in rats with CRF. KEY FINDINGS: The histopathological results showed that both WCF and CCF improved kidney injury and dysfunction of CRF rats, but WCF was more effective than CCF. Metabolic pathway analysis indicated that 24 metabolites and 5 major disturbed pathways associated with CCF, while WCF regulated 27 metabolites and 2 metabolic pathways. Bioinformatic analysis and network analysis revealed that 8 genes and 7 genes were regulated by CCF and WCF on CRF rats, respectively. The quantitative real-time polymerase chain reaction experiments verified the regulatory ability of CCF and WCF on the expression of 4 genes. CONCLUSIONS: An integrated strategy combined metabolomics, network analysis and bioinformatics was established to provide valuable holistic insight to explore the processing mechanism of TCMs.

Research hotspots and trend analysis of cell transplantation in traumatic spinal cord injury: a bibliometric and visualized analysis.

Background: A traumatic spinal cord injury (TSCI) can lead to severe nerve damage and disability. Cell transplantation therapy has shown great potential in the reconstruction of damaged spinal cords and promoting functional recovery. However, there is a lack of frontiers and futures analysis in the study of cell transplantation in TSCI. Methods: We used CiteSpace, VOSviewer and biblilometrix R package to perform bibliometric analysis on cell transplantation in TSCI from 2013 to 2023. Bibliometric records were extracted from English articles and reviews from the Web of Science core collection. Results: The bibliometric analysis included 284 papers published in 154 journals by 1,780 authors from 487 institutions in 41 countries and regions. The number of articles published in the past decade has fluctuated slightly, while the number of article citations has steadily increased. Mainland China and the United States are the leading countries and regions in this field, with the National Natural Science Foundation of China being the most funded foundation, and the United States being the country with the most funded articles. The University of Toronto in Canada is a prolific institution. Michael G. Fehlings has published the most articles, and D Michele Basso is the most cited author. Cell transplantation is the most published journal, and the Journal of Neurotrauma is the most cited journal. Cell and tissue engineering and clinical neurology are the basic disciplines in this field, and cutting-edge disciplines include developmental biology, biochemistry and molecular biology, and materials science and multidisciplinary. This study also helps scholars understand the current hotspots and future trends in this field. Marrow stromal cells, glial progenitor, and cell therapy are current research hotspots in this field, while nerve regeneration, cell therapy, and the safety of transplantation of transplantation may be potential research directions in the future. Conclusion: Cell transplantation after TSCI is receiving increasing attention. Cell therapy is both the frontier and a possible future trend in TSCI research. In addition, glial progenitor and marrow stromal cells are also current research hotspots. Meanwhile, nerve regeneration and safety of transplantation may be potential research directions. These findings will help further deepen research on cell transplantation for TSCI in scientific work.

Screening and Capability Assessment of Tyrosinase Inhibitors in Isodon excisoides by Ultrafiltration Coupled with UHPLC-Q-TOF-MS and Molecular Docking Technology.

Tyrosinase inhibitors can alleviate the harm to the liver caused by tyrosinase. How to effectively screen out natural tyrosinase inhibitors becomes a focus. In this study, Isodon excisoides was first extracted with the ultrasound optimized by response surface methodology. Then, a method combined ultrafiltration with ultra-liquid chromatography mass spectrometry (UHPLC/MS) was built to screen and identify tyrosinase inhibitors. The binding energies of active ingredients to tyrosinase were calculated by molecular docking. The reliability of the results was validated by the IC50 of enzyme inhibition assay. As a result, the binding energies of 7 components including excisanin B, lasiokaurin, rabdophyllin G, rabdoserrin B, rabdosin D, rabdosinate and weisiensin were lower than that of resveratrol. It was indicated that these components had high tyrosinase inhibitory activity. The IC50 values of lasiokaurin and excisanin B were 177 and 142 µmol/mL, which were less than that of resveratrol (183 µmol/mL). It showed that this way was simple, rapid, reliable and effective, which provided a new strategy to screen natural bioactive compounds from plants.

An Environmentally Adaptive and Contrastive Representation Learning Method for Condition Monitoring of Industrial Assets.

Condition monitoring of assets is significant to the efficiency and reliability of industrial automation systems. However, the accuracy of condition monitoring results is easily impaired by variational environments and volatile operations, especially for complex automation systems. In this article, an environmentally adaptive and contrastive representation learning method is proposed to address the problem. To suppress the unexpected effects of environmental variations on operating data, a regression model between the operational and environmental variables is developed. The variable regression adjustment is achieved by solving a penalized optimization problem based on spline functions, and the solution is explicitly derived. Then, negative samples and pseudo labels are generated based on the designed pattern of data augmentation, and valid data representations for asset condition monitoring can be obtained by contrastive learning. Moreover, the reference statue of healthy assets is established by kernel density estimation, and control charts are employed for online monitoring with alarm thresholds. Taking wind turbine blades as examples, the remarkable performance of the developed method is demonstrated with real-world measurements from wind farms. Furthermore, comparative analysis with benchmark approaches and ablation study are conducted to reveal the superiority and effectiveness of the proposed method.

Regulatory mechanisms of fatty acids biosynthesis in Armeniaca sibirica seed kernel oil at different developmental stages.

Background: Armeniaca sibirica seed kernel oil is rich in oleic acid and linoleic acid, thus holding potential value as a source of high-quality edible oils. However, some regulatory factors involved in fatty acids accumulation in A. sibirica seed kernels remain largely elusive. Thus, the aim of this study was to elucidate the regulatory mechanisms underlying fatty acids biosynthesis in A. sibirica developing seed kernels. Methods: Seed kernels from six plants from a single A. sibirica clone were taken at five different developmental stages (days 30, 41, 52, 63, and 73 after anthesis). Fatty acid composition in seed kernel oil was determined by gas chromatography-mass spectrometry (GC-MS). In addition, transcriptome analysis was conducted using second-generation sequencing (SGS) and single-molecule real-time sequencing (SMRT). Results: Rapid accumulation of fatty acids occurred throughout the different stages of seed kernels development, with oleic acid and linoleic acid as the main fatty acids. A total of 10,024, 9,803, 6,004, 6,719 and 9,688 unigenes were matched in the Nt, Nr, KOG, GO and KEGG databases, respectively. In the category lipid metabolism, 228 differentially expressed genes (DEGs) were annotated into 13 KEGG pathways. Specific unigenes encoding 12 key enzymes related to fatty acids biosynthesis were determined. Co-expression network analysis identified 11 transcription factors (TFs) and 13 long non-coding RNAs (lncRNAs) which putatively participate in the regulation of fatty acid biosynthesis. This study provides insights into the molecular regulatory mechanisms of fatty acids biosynthesis in A. sibirica developing seed kernels, and enabled the identification of novel candidate factors for future improvement of the production and quality of seed kernel oil by breeding.

Construction of a Hierarchical Gene Regulatory Network to Reveal the Drought Tolerance Mechanism of Shanxin Poplar.

Drought stress is a common adverse environment that plants encounter, and many drought-tolerant genes have been characterized. The gene regulatory network (GRN) is important in revealing the drought tolerance mechanism. Here, to investigate the regulatory mechanism of Shanxin poplar (Populus davidiana × P. bolleana) responding to drought stress, a three-layered GRN was built, and the regulatory relationship between genes in the GRN were predicted from expression correlation using a partial correlation coefficient-based algorithm. The GRN contains 1869 regulatory relationships, and includes 11 and 19 transcription factors (TFs) in the first and second layers, respectively, and 158 structural genes in the bottom layers involved in eight enriched biological processes. ChIP-PCR and qRT-PCR based on transient transformation were performed to validate the reliability of the GRN. About 88.0% of predicted interactions between the first and second layers, and 82.0% of predicted interactions between the second and third layers were correct, suggesting that the GRN is reliable. Six TFs were randomly selected from the top layer for characterizing their function in drought, and all of these TFs can confer drought tolerance. The important biological processes related to drought tolerance were identified, including "response to jasmonic acid", "response to oxidative stress", and "response to osmotic stress". In this GRN, PdbERF3 is predicted to play an important role in drought tolerance. Our data revealed the key regulators, TF-DNA interactions, and the main biological processes involved in adaption of drought stress in Shanxin poplar.

Genome-wide analysis of BpDof genes and the tolerance to drought stress in birch (Betula platyphylla).

BACKGROUND: DNA binding with one finger (Dof) proteins are plant-specific transcription factors playing vital roles in developmental processes and stress responses in plants. Nevertheless, the characterizations, expression patterns, and functions of the Dof family under drought stress (a key determinant of plant physiology and metabolic homeostasis) in woody plants remain unclear. METHODS: The birch (Betula platyphylla var. mandshuric) genome and plant TFDB database were used to identify Dof gene family members in birch plants. ClustalW2 of BioEdit v7.2.1, MEGA v7.0, ExPASy ProtParam tool, Subloc, TMHMM v2.0, GSDS v2.0, MEME, TBtools, KaKs Calculator v2.0, and PlantCARE were respectively used to align the BpDof sequences, build a phylogenetic tree, identify the physicochemical properties, analyze the chromosomal distribution and synteny, and identify the cis-elements in the promoter regions of the 26 BpDof genes. Additionally, the birch seedlings were exposed to PEG6000-simulated drought stress, and the expression patterns of the BpDof genes in different tissues were analyzed by qRT-PCR. The histochemical staining and the evaluation of physiological indexes were performed to assess the plant tolerance to drought with transient overexpression of BpDof4, BpDof11, and BpDof17 genes. SPSS software and ANOVA were used to conduct all statistical analyses and determine statistically significant differences between results. RESULTS: A total of 26 BpDof genes were identified in birch via whole-genome analysis. The conserved Dof domain with a C(x)2C(x)21C(x)2C zinc finger motif was present in all BpDof proteins. These birch BpDofs were classified into four groups (A to D) according to the phylogenetic analysis of Arabidopsis thaliana Dof genes. BpDof proteins within the same group mostly possessed similar motifs, as detected by conserved motif analysis. The exon-intron analysis revealed that the structures of BpDof genes differed, indicating probable gene gain and lose during the BpDof evolution. The chromosomal distribution and synteny analysis showed that the 26 BpDofs were unevenly distributed on 14 chromosomes, and seven duplication events among six chromosomes were found. Cis-acting elements were abundant in the promoter regions of the 26 BpDof genes. qRT-PCR revealed that the expression of the 26 BpDof genes was differentially regulated by drought stress among roots, stems, and leaves. Most BpDof genes responded to drought stress, and BpDof4, BpDof11, and BpDof17- were significantly up-regulated. Therefore, plants overexpressing these three genes were generated to investigate drought stress tolerance. The BpDof4-, BpDof11-, and BpDof17--overexpressing plants showed promoted reactive oxygen species (ROS) scavenging capabilities and less severe cell damage, suggesting that they conferred enhanced drought tolerance in birch. This study provided an in-depth insight into the structure, evolution, expression, and function of the Dof gene family in plants.

Oral Bioavailability and Lymphatic Transport of Pueraria Flavone-Loaded Self-Emulsifying Drug-Delivery Systems Containing Sodium Taurocholate in Rats.

We developed self-microemulsifying drug-delivery systems (SMEDDS), including bile salts, to improve the oral bioavailability of pueraria flavones (PFs). The physical properties of the SMEDDS using Cremophor RH 40, and bile salts as mixed surfactants at weight ratios of 10:0⁻0:10 were determined. The particle sizes of PFs-SMEDDSNR containing sodium taurocholate (NaTC) and Cremophor RH 40, and PFs-SMEDDSR containing Cremophor RH 40 were measured upon dilution with deionized water and other aqueous media. Dilution volume presented no remarkable effects on particle size, whereas dilution media slightly influenced particle size. PFs-SMEDDSNR and PFs-SMEDDSR provided similar release rates in pH-1.2 hydrochloride solution. However, the release rate of PFs-SMEDDSNR was faster than that of PFs-SMEDDSR in pH-6.8 phosphate buffer containing 20 mM NaTC and 500 U/mL porcine pancreas lipase. The pharmacokinetics and bioavailability were measured in rats. The oral bioavailability of PFs-SMEDDSNR was 2.57- and 2.28-fold that of a suspension of PFs (PFs-suspension) before and after the blockade of the lymphatic transport route by cycloheximide, respectively. These results suggested PFs-SMEDDSNR could significantly improve the oral relative absorption of PFs via the lymphatic uptake pathway. SMEDDS containing NaTC may provide an effective approach for enhancing the oral bioavailability of PFs.

Evaluation of the cytotoxicity and intestinal absorption of a self-emulsifying drug delivery system containing sodium taurocholate.

Currently, many surfactants used in self-emulsifying drug delivery systems (SMEDDS) can cause gastrointestinal mucosal irritation and systemic toxicity. In the present study, SMEDDS were loaded with pueraria flavones, using sodium taurocholate to replace polyoxyl 40 dydrogenated castor oil (Cremophor® RH 40) as the surfactant (PF-SMEDDSNR) to reduce the toxicity of SMEDDS using Cremophor® RH 40 as the surfactant (PF-SMEDDSR). The absorption rate constants (Ka) and intestinal permeability coefficients (Peff) were measured. The effects of P-glycoprotein inhibitor (verapamil), adenosine triphosphate (ATP) inhibitor (2,4-dinitrophenol), and carrier inhibitor on Ka and Peff values in the ileum were determined. Biological safety was also evaluated. The Ka and Peff values increased for PF-solution concentrations of 200µg/ml>100µg/ml>400µg/ml in individual segments of the intestines. The results indicated that Peff values of PF-SMEDDSNR were distinctly higher than those of SMEDDS loaded with pueraria flavones using Cremophor®RH 40 as the surfactant (PF-SMEDDSR) and PF-solution in four intestinal segments. However, the Ka values of PF-SMEDDSNR were higher only in the jejunum and ileum segments compared with those of PF-SMEDDSR and PF-solution. The Ka and Peff values without verapamil were significantly lower than those with verapamil. 2,4-Dinitrophenol had no effect on Ka and Peff values. The Ka and Peff values of PF-SMEDDSNR significantly decreased after perfusing B-SMEDDSNR for 1h prior to the study. The cell viabilities after exposure to SMEDDSNR were higher than those of SMEDDSR in the range of 81-324µg/ml. Lactate dehydrogenase release from cells treated with PF-SMEDDSNR or B-SMEDDSNR was significantly lower than that from cells treated with PF-SMEDDSR or B-SMEDDSR at surfactant concentrations of 243 and 324µg/ml. However, there were no differences with SMEDDS treatment at surfactant concentrations of 0-162µg/ml. Hence, we conclude that SMEDDS using sodium taurocholate as the surfactant can reduce the toxicity of SMEDDS, meanwhile, maintain the characteristics of SMEDDS, and enhance intestinal absorption.

Enhanced Oral Bioavailability of Pueraria Flavones by a Novel Solid Self-microemulsifying Drug Delivery System (SMEDDS) Dropping Pills.

To improve bioavailability of pueraria flavones (PF), a self-microemulsifying drug delivery system (SMEDDS) dropping pills composed of PF, Crodamol GTCC, Maisine 35-1, Cremophor RH 40, 1,2-propylene glycol and polyethylene glycol 6000 (PEG6000) was developed. Particle size, zeta potential, morphology and in vitro drug release were investigated, respectively. Pharmacokinetics, bioavailability of PF-SMEDDS dropping pills and commercial Yufengningxin dropping pills were also evaluated and compared in rats. Puerarin treated as the representative component of PF was analyzed. Dynamic light scattering showed the ability of PF-SMEDDS dropping pills to form a nanoemulsion droplet size in aqueous media. The type of media showed no significant effects on the release rate of PF. PF-SMEDDS dropping pills were able to improve the in vitro release rate of PF, and the in vitro release of these dropping pills was significantly faster than that of Yufengningxin dropping pills. There was a dramatic difference between the mean value of t1/2, peak concentration (Cmax), the area of concentration-time curve from 0 to 6 h (AUC0-6 h) of PF-SMEDDS dropping pills and that of commercial Yufengningxin dropping pills. A pharmacokinetic study showed that the bioavailability of PF was greatly enhanced by PF-SMEDDS dropping pills. The value of Cmax and relative bioavailability of PF-SMEDDS dropping pills were dramatically improved by an average of 1.69- and 2.36-fold compared with that of Yufengningxin dropping pills after gavage administration, respectively. It was concluded that bioavailability of PF was greatly improved and that PF-SMEDDS dropping pills might be an encouraging strategy to enhance the oral bioavailability of PF.