Genome-wide identification of GH28 family and insight into its contributions to pod shattering resistance in Brassica napus L.

Rapeseed (Brassica napus L.), accounts for nearly 16% of vegetable oil, is the world's second produced oilseed. However, pod shattering has caused significant yield loses in rapeseed production, particularly during mechanical harvesting. The GH28 genes can promote pod shattering by changing the structure of the pod cell wall in Arabidopsis. However, the role of the GH28 gene family in rapeseed was largely unknown. Therefore, a genome-wide comprehensive analysis was conducted to classify the role of GH28 gene family on rapeseed pod shattering. A total of 37 BnaGH28 genes in the rapeseed genome were identified. These BnaGH28s can be divided into five groups (Group A-E), based on phylogenetic and synteny analysis. Protein property, gene structure, conserved motif, cis-acting element, and gene expression profile of BnaGH28 genes in the same group were similar. Specially, the expression level of genes in group A-D was gradually decreased, but increased in group E with the development of silique. Among eleven higher expressed genes in group E, two BnaGH28 genes (BnaA07T0199500ZS and BnaC06T0206500ZS) were significantly regulated by IAA or GA treatment. And the significant effects of BnaA07T0199500ZS variation on pod shattering resistance were also demonstrated in present study. These results could open a new window for insight into the role of BnaGH28 genes on pod shattering resistance in rapeseed.

Genome-wide characterization of SDR gene family and its potential role in seed dormancy of Brassica napus L.

Rapeseed (Brassica napus L.) with short or no dormancy period are easy to germinate before harvest (pre-harvest sprouting, PHS). PHS has seriously decreased seed weight and oil content in B. napus. Short-chain dehydrogenase/ reductase (SDR) genes have been found to related to seed dormancy by promoting ABA biosynthesis in rice and Arabidopsis. In order to clarify whether SDR genes are the key factor of seed dormancy in B. napus, homology sequence blast, protein physicochemical properties, conserved motif, gene structure, cis-acting element, gene expression and variation analysis were conducted in present study. Results shown that 142 BnaSDR genes, unevenly distributed on 19 chromosomes, have been identified in B. napus genome. Among them, four BnaSDR gene clusters present in chromosome A04、A05、C03、C04 were also identified. These 142 BnaSDR genes were divided into four subfamilies on phylogenetic tree. Members of the same subgroup have similar protein characters, conserved motifs, gene structure, cis-acting elements and tissue expression profiles. Specially, the expression levels of genes in subgroup A, B and C were gradually decreased, but increased in subgroup D with the development of seeds. Among seven higher expressed genes in group D, six BnaSDR genes were significantly higher expressed in weak dormancy line than that in nondormancy line. And the significant effects of BnaC01T0313900ZS and BnaC03T0300500ZS variation on seed dormancy were also demonstrated in present study. These findings provide a key information for investigating the function of BnaSDRs on seed dormancy in B. napus.

Impact of preoperative [18F]FDG PET/CT vs. contrast-enhanced CT in the staging and survival of patients with clinical stage I and II non-small cell lung cancer: a 10-year follow-up study.

OBJECTIVES: To elucidate the impact of [18F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC. METHODS: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis. RESULTS: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90). CONCLUSION: Addition of preoperative [18F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy.

Parameter optimization analysis of rotary electromagnetic vibration energy harvester for performance enhancement under free vibration.

In this paper, three new important aspects of rotary electromagnetic vibration energy harvesting technology (RE-VEH) are concerned and investigated: (i) vibro-electric coupling mechanism of the RE-VEH system is studied through theoretical modeling; (ii) quantitative analysis of system parameters based on numerical simulation method is carried out for the optimal design of RE-VEH; and (iii) dynamic power output performance of the RE-VEH system in free vibration is discussed. The parameter adjusting methods of the RE-VEH system in free vibration mode are obtained through theoretical analysis and numerical simulation. The experimental results show that the power output performance of RE-VEH in free vibration mode matches the numerical simulation results. The simulation and experimental results show that the maximum voltage output and power output of the RE-VEH with different structure parameters under free vibration can be up to the level of 100∼101 V/watt. The above results indicate that RE-VEH in a free vibration environment has significant energy output performance.

Identification and Expression Analysis of DFR Gene Family in Brassica napus L.

Dihydroflavonol 4-reductase (DFR) is a key enzyme in the flavonoid biosynthetic pathway and is essential for the formation of plants' color. In this study, 26 BnDFR genes were identified using 6 Arabidopsis DFR genes as reference. The physicochemical properties, subcellular localization, and conserved structure of BnDFR proteins were analyzed; the evolutionary relationship, collinearity analysis, and expression characteristics of BnDFR genes were studied; and the correlation between the expression level of BnDFR genes and anthocyanin content in rape petals were analyzed. The results showed that the 26 BnDFRs were located in chloroplasts, cytoplasm, nuclei, and mitochondria, distributed on 17 chromosomes, and divided into 4 groups; members of the same group have a similar function, which may be related to the environmental response elements and plant hormone response elements. Intraspecific collinearity analysis showed 51 pairs of collinear genes, and interspecific collinearity analysis showed 30 pairs of collinear genes. Analysis of the expression levels of BnDFRs and anthocyanin content in different color rape petals showed that BnDFR6 and BnDFR26 might play an important role in the synthesis of anthocyanins in rape petals. This provides theoretical guidance for further analysis of the anthocyanin anabolism mechanism involved in the DFR gene in Brassica napus.

Jujuboside A ameliorates cognitive deficiency in delirium through promoting hippocampal E4BP4 in mice.

OBJECTIVE: Delirium (acute brain syndrome) is a common and serious neuropsychiatric disorder characterized by an acute decline in cognitive function. However, there is no effective treatment clinically. Here we investigated the potential effect of jujuboside A (JuA, a natural triterpenoid saponin) on cognitive impairment in delirium. METHODS: Delirium models of mice were established by injecting lipopolysaccharide (LPS) plus midazolam and implementing a jet lag protocol. Novel object recognition test and Y maze test were used to evaluate the effects of JuA on delirium-associated cognitive impairment. The mRNA and protein levels of relevant clock factors and inflammatory factors were measured by qPCR and Western blotting. Hippocampal Iba1+ intensity was determined by immunofluorescence staining. KEY FINDINGS: JuA ameliorated delirium (particularly delirium-associated cognitive impairment) in mice, which was proved by the behavioural tests, including a preference for new objects, an increase of spontaneous alternation and improvement of locomotor activity. Furthermore, JuA inhibited the expression of ERK1/2, p-p65, TNFα and IL-1ß in hippocampus, and repressed microglial activation in delirious mice. This was attributed to the increased expression of E4BP4 (a negative regulator of ERK1/2 cascade and microglial activation). Moreover, loss of E4bp4 in mice abrogated the effects of JuA on delirium as well as on ERK1/2 cascade and microglial activation in the hippocampus of delirious mice. Additionally, JuA treatment increased the expression of E4BP4 and decreased the expression of p-p65, TNFα and IL-1ß in LPS-stimulated BV2 cells, supporting a protective effect of JuA on delirium. CONCLUSIONS: JuA protects against delirium-associated cognitive impairment through promoting hippocampal E4BP4 in mice. Our findings are of great significance to the drug development of JuA against delirium and related disorders.

Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors.

In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in "cold tumors" with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this review, we provide an updated overview of the progress made in recent years concerning ICB therapy assisted by FUS-controlled small-molecule delivery systems. We highlight the value of different FUS-augmented small-molecules delivery systems to ICB and describe the synergetic effects and underlying mechanisms of these combination strategies. Furthermore, we discuss the limitations of the current strategies and the possible ways that FUS-mediated small-molecule delivery systems could boost novel personalized ICB treatments for solid tumors.

[Ecological Risk and Migration Patterns of Heavy Metals in Soil and Crops in the Lead-Zinc Mining Area in Guizhou, China].

An accumulation of heavy metals in soil poses a risk to the ecological environment and human health. In this study, the concentrations of heavy metals in soil and crops were examined in a lead-zinc mining area in Guizhou Province, China. The distribution and sources of heavy metals were analyzed using GIS spatial mapping. The potential ecological risks of heavy metals were assessed using the potential ecological risk index (RI), and the human health risk assessment method recommended by the United States Environmental Protection Agency (USEPA) was used to quantify the health risk of residents exposed to heavy metals in the soil around lead-zinc mines. According to the results, the average of concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the soil were 58, 7.9, 175, 64, 0.461, 65, 1539, and 2513 mg·kg-1, respectively, which were significantly higher than the background values in Guizhou Province. It was found that the As, Cd, Cu, Hg, Pb, and Zn concentrations were extremely irregular in the soil and that the concentrations decreased significantly with the distance to the smelters, which were greatly disturbed by human activities. Comprehensive evaluation of soil heavy metals using the potential ecological risk index revealed that the risks of soil heavy metals were pole-strength and strong levels, and Cd constituted the primary ecological risk factor. A total of 22% and 10% of the corn samples contained Pb and As above the heavy metal pollution thresholds in the national food safety standards. According to human health risk assessments, heavy metals in the soil present potential non-carcinogenic risks to adults or children, and pose a potential carcinogenic risk to children. Soil pH was an important controlling factor affecting the bioavailability, migration, and accumulation of Cd in soil-crop systems. This study provides data and theoretical support for the prevention and control of soil pollution in lead-zine mining areas.

Reprogramming of rhythmic liver metabolism by intestinal clock.

BACKGROUND & AIMS: Temporal oscillations in intestinal nutrient processing and absorption are coordinated by the local clock, which leads to the hypothesis that the intestinal clock has major impacts on shaping peripheral rhythms via diurnal nutritional signals. Here, we investigate the role of the intestinal clock in controlling liver rhythmicity and metabolism. METHODS: Transcriptomic analysis, metabolomics, metabolic assays, histology, quantitative (q)PCR, and immunoblotting were performed with Bmal1-intestine-specific knockout (iKO), Rev-erba-iKO, and control mice. RESULTS: Bmal1 iKO caused large-scale reprogramming of the rhythmic transcriptome of mouse liver with a limited effect on its clock. In the absence of intestinal Bmal1, the liver clock was resistant to entrainment by inverted feeding and a high-fat diet. Importantly, Bmal1 iKO remodelled diurnal hepatic metabolism by shifting to gluconeogenesis from lipogenesis during the dark phase, leading to elevated glucose production (hyperglycaemia) and insulin insensitivity. Conversely, Rev-erba iKO caused a diversion to lipogenesis from gluconeogenesis during the light phase, resulting in enhanced lipogenesis and an increased susceptibility to alcohol-related liver injury. These temporal diversions were attributed to disruption of hepatic SREBP-1c rhythmicity, which was maintained via gut-derived polyunsaturated fatty acids produced by intestinal FADS1/2 under the control of a local clock. CONCLUSIONS: Our findings establish a pivotal role for the intestinal clock in dictating liver rhythmicity and diurnal metabolism, and suggest targeting intestinal rhythms as a new avenue for improving metabolic health. IMPACT AND IMPLICATIONS: Our findings establish the centrality of the intestinal clock among peripheral tissue clocks, and associate liver-related pathologies with its malfunction. Clock modifiers in the intestine are shown to modulate liver metabolism with improved metabolic parameters. Such knowledge will help clinicians improve the diagnosis and treatment of metabolic diseases by incorporating intestinal circadian factors.

Whole-Genome Comparison Reveals Structural Variations behind Heading Leaf Trait in Brassica oleracea.

Brassica oleracea displays remarkable morphological variations. It intrigued researchers to study the underlying cause of the enormous diversification of this organism. However, genomic variations in complex heading traits are less known in B. oleracea. Herein, we performed a comparative population genomics analysis to explore structural variations (SVs) responsible for heading trait formation in B. oleracea. Synteny analysis showed that chromosomes C1 and C2 of B. oleracea (CC) shared strong collinearity with A01 and A02 of B. rapa (AA), respectively. Two historical events, whole genome triplication (WGT) of Brassica species and differentiation time between AA and CC genomes, were observed clearly by phylogenetic and Ks analysis. By comparing heading and non-heading populations of B. oleracea genomes, we found extensive SVs during the diversification of the B. oleracea genome. We identified 1205 SVs that have an impact on 545 genes and might be associated with the heading trait of cabbage. Overlapping the genes affected by SVs and the differentially expressed genes identified by RNA-seq analysis, we identified six vital candidate genes that may be related to heading trait formation in cabbage. Further, qRT-PCR experiments also verified that six genes were differentially expressed between heading leaves and non-heading leaves, respectively. Collectively, we used available genomes to conduct a comparison population genome analysis and identify candidate genes for the heading trait of cabbage, which provides insight into the underlying reason for heading trait formation in B. oleracea.

Genome-Wide Identification and Functional Characterization of Stress Related Glyoxalase Genes in Brassica napus L.

Rapeseed (Brassica napus L.) is not only one of the most important oil crops in the world, but it is also an important vegetable crop with a high value nutrients and metabolites. However, rapeseed is often severely damaged by adverse stresses, such as low temperature, pathogen infection and so on. Glyoxalase I (GLYI) and glyoxalase II (GLYII) are two enzymes responsible for the detoxification of a cytotoxic metabolite methylglyoxal (MG) into the nontoxic S-D-lactoylglutathione, which plays crucial roles in stress tolerance in plants. Considering the important roles of glyoxalases, the GLY gene families have been analyzed in higher plans, such as rice, soybean and Chinese cabbage; however, little is known about the presence, distribution, localizations and expression of glyoxalase genes in rapeseed, a young allotetraploid. In this study, a total of 35 BnaGLYI and 30 BnaGLYII genes were identified in the B. napus genome and were clustered into six and eight subfamilies, respectively. The classification, chromosomal distribution, gene structure and conserved motif were identified or predicted. BnaGLYI and BnaGLYII proteins were mainly localized in chloroplast and cytoplasm. By using publicly available RNA-seq data and a quantitative real-time PCR analysis (qRT-PCR), the expression profiling of these genes of different tissues was demonstrated in different developmental stages as well as under stresses. The results indicated that their expression profiles varied among different tissues. Some members are highly expressed in specific tissues, BnaGLYI11 and BnaGLYI27 expressed in flowers and germinating seed. At the same time, the two genes were significantly up-regulated under heat, cold and freezing stresses. Notably, a number of BnaGLY genes showed responses to Plasmodiophora brassicae infection. Overexpression of BnGLYI11 gene in Arabidopsis thaliana seedlings confirmed that this gene conferred freezing tolerance. This study provides insight of the BnaGLYI and BnaGLYII gene families in allotetraploid B. napus and their roles in stress resistance, and important information and gene resources for developing stress resistant vegetable and rapeseed oil.

Sodium hydrosulfide alleviates aluminum toxicity in Brassica napus through maintaining H2S, ROS homeostasis and enhancing aluminum exclusion.

Hydrogen sulfide (H2S) is a gaseous mediator that plays versatile roles in plant growth and stress responses. However, the regulatory functions of H2S in plant responses to aluminum (Al) stress remain elusive. We observed that application of 20 µM of NaHS (H2S donor) or 0.2 mM of hypotaurine (HT, H2S scavenger) significantly mitigated the inhibition of rapeseed root growth caused by Al stress (150 µM). Exposure to Al for 6 h induced significant H2S accumulation and high levels were maintained thereafter, owing to the elevation of cysteine (83.73 %), L-cysteine desulfhydrase (LCD, 92.32 %), and cyanoalanine synthase (CAS, 11.23 %), and the inhibition of O-Acetyl-l-serine (thiol) lyase (OAS-TL, 15.13 %). Addition of HT significantly scavenged the prolonged H2S accumulation caused by Al stress. Exogenous NaHS maintained the H2S homeostasis through increasing OAS-TL activity (34.99 %) and inhibiting LCD activity (25.72 %), and cysteine level (39.53 %). Moreover, exogenous NaHS mitigated oxidative damage by enhancing antioxidant enzyme activity (SOD 26.27 %, POD 28.62 %, CAT 400.5 % and APX 92.68 %) and proline content (19.85 %). It also decreased root cell wall Al accumulation (20.52 %) by decreasing PME activity (24.64 %) and facilitating pectin methylation (16.74 %). Similar alleviative effects were observed when HT was added. These results suggest that H2S functions differential roles in Al stress response in rapeseed seedlings, depending on its local concentration and duration. Prolonged high H2S emissions might contribute to Al toxicity, while moderate exogenous H2S improves Al tolerance through controlling H2S and ROS accumulation and enhancing Al exclusion through replenishing antioxidant reservoirs and facilitating pectin methylation. It is therefore important that further study investigates how to orchestrate endogenous H2S levels and improve plant stress tolerance.

Photo-crosslinked GelMA loaded with dental pulp stem cells and VEGF to repair critical-sized soft tissue defects in rats.

BACKGROUND: Tissue engineering of skin and mucosa is essential for the esthetic and functional reconstruction of individuals disfigured by trauma, resection surgery, or severe burns while overcoming the limited amount of autograft and donor site morbidity. PURPOSE: We aimed to determine whether a combination of Gelatin-methacryloyl (GelMA) hydrogel scaffold alone or loaded with either dental pulp stem cells (DPSCs) and/or vascular endothelial growth factor (VEGF) could improve skin wound healing in rats. MATERIALS AND METHODS: Four 10 mm full-thickness skin defects were created on the dorsum of 15 Sprague-Dawley rats. The wounds were treated with GelMA alone, GelMA+DPSCs, or GelMA+DPSCs+VEGF. Unprotected wounds were used as controls. Animals were euthanized at 1-, 2-, and 4 weeks post-surgery, and the healing wounds were harvested for clinical, histological, and RT-PCR analysis. RESULTS: No signs of clinical inflammation were observed among all groups. Few and sparse mononuclear inflammatory cells were observed in GelMA+DPSCs and GelMA+DPSCs+VEGF groups at 2 weeks, with complete epithelialization of the wounds. At 4 weeks, the epidermis in GelMA+DPSCs and GelMA+DPSCs+VEGF groups was indistinguishable from the empty defect and GelMA groups. The decrease in cellularity and increase in density of collagen fibers were observed over time in both GelMA+DPSCs and GelMA+DPSCs+VEGF groups but were more evident in the GelMA+DPSCs+VEGF group. The GelMA+DPSCs+VEGF group showed a higher expression of the KER 10 gene at all time points compared with the other groups. Expression of Col1 A1 and TGFß-1 were not statistically different over time neither among the groups. CONCLUSION: GelMA scaffolds loaded with DPSCs, and VEGF accelerated the re-epithelialization of skin wounds.

Tangeretin prevents cognitive deficit in delirium through activating RORα/γ-E4BP4 axis in mice.

Delirium is a common and serious neuropsychiatric syndrome characterized with acute cognitive and attentional deficits, however, the effective therapies are lacking. Here, using mouse models of delirium, we investigated the effects of tangeretin (TAN, a natural flavonoid) on cognitive impairment by assessing object preference with novel object recognition (NOR) test and spontaneous alternation with Y maze test. We found that TAN, as a RORα/γ agonist, prevented cognitive decline in delirious mice as evidenced by a normal novel object preference and increased spontaneous alternation. This was accompanied by decreased expression of ERK1/2, TNFα and IL-1ß as well as diminished microglial activation in delirious mice. The protective effect of TAN on delirium was mainly attributed to increased hippocampal E4BP4 expression (a known target of RORs and a regulator of cognition in delirium through modulating the ERK1/2 cascade and microglial activation) via activation of RORα/γ. In addition, TAN treatment modulated the expression of RORα/γ target genes (such as E4bp4 and Bmal1) and inhibited the expression of TNFα and IL-1ß in lipopolysaccharide (LPS)-stimulated cells, supporting a beneficial effect of TAN on delirium. In conclusion, TAN is identified as a RORα/γ agonist which promotes E4BP4 expression to prevent cognitive decline in delirious mice. Our findings may have implications for drug development of TAN for prevention and treatment of various diseases associated with cognitive deficiency.

Heavy Metal Pollution and Source Contributions in Agricultural Soils Developed from Karst Landform in the Southwestern Region of China.

Heavy metal pollution of soil in agricultural areas is the most prominent environmental pollution problem in China, seriously affecting human health and food security. It has become one of the environmental problems to which all sectors of society attach great importance. Soil heavy metals in the weathering area of hazardous geological bodies in southwest China have naturally high background attributes. Therefore, ecological risk assessment and analysis of potential sources of soil heavy metals in southwest China is of great significance for soil health management, soil heavy metal pollution control and territorial spatial planning. In this study, we collected 787 soil samples (0-20 cm) in Xuanwei County in China and analyzed the concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb and Zn in soils. Igeo, RI, HI and CR were used to calculate the pollution levels, ecological risks and human health risks. Additionally, the PMF model and one-way ANOVA were used to identify the potential sources and discuss the factors affecting the enrichment of heavy metals. The results showed that the mean contents of the surface soils were 1.190 (Cd), 139.4 (Cr), 96.74 (Cu), 0.081 (Hg), 56.97 (Ni), 46.66 (Pb) and 130.1 (Zn) mg/kg. All heavy metals exceeded the background values of the A layer soil in Yunnan Province. The Igeo showed that Cd was the most hazardous element in the study area, followed by Cu, Cr, As, Ni and Pb. The RI showed that low ecological risks, moderate ecological risks, considerable ecological risks and strong ecological risks accounted for 3.81%, 55.27%, 37.74% and 3.18%, respectively, of the total samples, and Cd was the main dominant element. The HI values of the As element in children were greater than 1, indicating a non-carcinogenic risk, and other elements' risks were acceptable. The CR values of Cr and Ni were higher than their limits (1 × 10-4), and both had carcinogenic risks in children and adults, as did As in children. According to the PMF model, four heavy metals sources were identified: geological sources (32%), sources from mining activities (19.38%), atmospheric deposition sources (17.57%) and agricultural sources (31.05%). Thereinto, As and Pb were mainly derived from agricultural sources, Cd and Cr were mainly associated with geological sources, Cu was largely from mining activity sources, Hg was mainly from atmospheric deposition sources and Ni and Zn were mainly from geological sources, mining activities and agricultural activities. The parent material has a significant influence on the enrichment of heavy metals in the soil, and the heavy metals are significantly enriched in the carbonate parent material and quaternary parent material. Topography also plays a role in heavy metal accumulation; Cd, Cr, Cu, Ni and Zn gradually decreased with the increase in altitude, and As and Pb increased with the increase in altitude. Mn-oxide played a crucial part in the enrichment of Cu and Zn, while SOC, K2O and pH had little influence on the accumulation of heavy metals.

The nuclear receptor REV-ERBα regulates CYP2E1 expression and acetaminophen hepatotoxicity.

CYP2E1 plays an important role in drug metabolism and drug-induced hepatotoxicity. Here, we aimed to investigate a potential role for the nuclear receptor REV-ERBα in regulation of CYP2E1 expression and acetaminophen (APAP)-induced hepatotoxicity, and to determine the underlying mechanisms.Regulatory effects of REV-ERBα on CYP2E1 expression were assessed in vivo (using Rev-erbα-/- mice) and in vitro (using AML12 and HepG2 cells). In vitro microsomal CYP2E1 activity was probed using its specific substrate p-nitrophenol. Pharmacokinetic and acute toxicity studies were performed with Rev-erbα-/- and wild-type mice after APAP administration.We found that Rev-erbα ablation led to decreases in hepatic CYP2E1 expression and activity in mice. In line with this, APAP-induced hepatotoxicity was attenuated in Rev-erbα-deficient mice. The attenuated toxicity was due to down-regulation of APAP metabolism mediated by CYP2E1, which was evidenced by a decrease in formation of the toxic intermediate metabolite NAPQI (i.e. reduced APAP-cysteine and APAP-N-acetylcysteine levels). Furthermore, positive regulation of CYP2E1 expression by REV-ERBα was confirmed in both AML12 and HepG2 cells. Based on luciferase reporter assays, it was found that REV-ERBα regulated Cyp2e1 transcription and expression through repression of DEC2.In conclusion, REV-ERBα positively regulates CYP2E1 expression in mice, thereby affecting APAP metabolism and hepatotoxicity.

Human Umbilical Vein Endothelial Cells Survive on the Ischemic TCA Cycle under Lethal Ischemic Conditions.

It is generally believed that vascular endothelial cells (VECs) rely on glycolysis instead of the tricarboxylic acid (TCA) cycle under both normoxic and hypoxic conditions. However, the metabolic pattern of human umbilical vein endothelial cells (HUVECs) under extreme ischemia (hypoxia and nutrient deprivation) needs to be elucidated. We initiated a lethal ischemic model of HUVECs, performed proteomics and bioinformatics, and verified the metabolic pattern shift of HUVECs. Ischemic HUVECs displayed extensive aerobic respiration, including upregulation of the TCA cycle and mitochondrial respiratory chain in mitochondria and downregulation of glycolysis in cytoplasm. The TCA cycle was enhanced while the cell viability was decreased through the citrate synthase pathway when substrates of the TCA cycle (acetate and/or pyruvate) were added and vice versa when inhibitors of the TCA cycle (palmitoyl-CoA and/or avidin) were applied. The inconsistency of the TCA cycle level and cell viability suggested that the extensive TCA cycle can keep cells alive yet generate toxic substances that reduce cell viability. The data revealed that HUVECs depend on "ischemic TCA cycle" instead of glycolysis to keep cells alive under lethal ischemic conditions, but consideration must be given to relieve cell injury.

E4BP4 Coordinates Circadian Control of Cognition in Delirium.

Improved understanding of the etiologies of delirium, a common and severe neuropsychiatric syndrome, would facilitate the disease prevention and treatment. Here, the authors invesitgate the role of circadian rhythms in the pathogenesis of delirium. They observe perturbance of circadian rhythms in mouse models of delirium and disrupted clock gene expression in patients with delirium. In turn, physiological and genetic circadian disruptions sensitize mice to delirium with aggravated cognitive impairment. Likewise, global deletion of E4bp4 (E4 promoter-binding protein), a clock gene markedly altered in delirium conditions, results in exacerbated delirium-associated cognitive decline. Cognitive decline in delirium models is attributed to microglial activation and impaired long-term potentiation in the hippocampus. Single-cell RNA-sequencing reveals microglia as the regulatory target of E4bp4. E4bp4 restrains microglial activation via inhibiting the ERK1/2 signaling pathway. Supporting this, mice lacking in microglial E4bp4 are delirious prone, whereas mice with E4bp4 specifically deleted in hippocampal CA1 neurons have a normal phenotype. Mechanistically, E4bp4 inhibits ERK1/2 signaling by trans-repressing Mapk1/3 (genes encoding ERK1/2) via direct binding to a D-box element in the promoter region. These findings define a causal role of clock dysfunction in delirium development and indicate E4bp4 as a regulator of cognition at the crosstalk between circadian clock and delirium.

Genomic selection and genetic architecture of agronomic traits during modern rapeseed breeding.

Rapeseed (Brassica napus L.) is an important oil-producing crop for the world. Its adaptation, yield and quality have been considerably improved in recent decades, but the genomic basis underlying successful breeding selection remains unclear. Hence, we conducted a comprehensive genomic assessment of rapeseed in the breeding process based on the whole-genome resequencing of 418 diverse rapeseed accessions. We unraveled the genomic basis for the selection of adaptation and agronomic traits. Genome-wide association studies identified 628 associated loci-related causative candidate genes for 56 agronomically important traits, including plant architecture and yield traits. Furthermore, we uncovered nonsynonymous mutations in plausible candidate genes for agronomic traits with significant differences in allele frequency distributions across the improvement process, including the ribosome recycling factor (BnRRF) gene for seed weight. This study provides insights into the genomic basis for improving rapeseed varieties and a valuable genomic resource for genome-assisted rapeseed breeding.

[Sources Identification, Ecological Risk Assessment, and Controlling Factors of Potentially Toxic Elements in Typical Lead-Zinc Mine Area, Guizhou Province, Southwest China].

Carbonatite and basalt are widely distributed in southwest China, and potentially toxic elements (PTEs) are associated with the naturally high background properties. It is important to carry out ecological risk assessments and identify potential sources of PTEs. A total of 3180 soil samples (0-20 cm) were collected in Hezhang county, a typical high background area of PTEs with the parent lithology of carbonatite and basalt. Samples were obtained from 18 large lead-zinc mines, which belong to a multi-ecological risk superimposed area with high ecological risk. The concentration of PTEs (Cd, Cr, As, Hg, Pb, Cu, Zn, and Ni) in the topsoil were analyzed, and statistical analysis (SA), geographic information system (GIS), enrichment factor (EF), potential ecological risk index (RI), and positive matrix factorization (PMF) methods were used to assess the ecological risk and quantify sources of PTEs. The mean values of PTEs concentrations in topsoil were 24.55, 2.25, 176.40, 89.60, 0.19, 64.20, 102.00, and 257.00 mg·kg-1 for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, respectively, which were remarkably higher than the average background value (ABV) of soils in Guizhou Province. The average concentrations of Cd, Cr, Cu, Ni, Pb, and Zn exceeded the screening values specified for the soil contamination risk in agricultural land (GB 15618-2018) by 7.50, 1.18, 1.79, 1.07, 1.40, and 1.29 times, respectively. The EF showed that Cd had a large area of moderate pollution; Pb, Zn, and Cu had a small area of slight pollution; the EFs values of Hg, Cr, Ni, and As were near the baseline value (EF≈1), and contaminations were slight or nonexistent. The PMF indicated that there were five sources, namely pyrite mines, lead-zinc mines, natural sources of basalt and carbonatite, and agricultural activities; the risk contribution ratios were 5.25%, 27.37%, 28.94%, 17.91%, and 20.53%, respectively. The most toxic coefficients of Hg and Cd were mainly natural sources, with contribution ratios of 86.3% and 72.7%, respectively. The soil samples in the mining areas expectedly contained high ratios of Zn/Cd and Pb/Cd, which confirmed that PTEs in the soil were mainly derived from the smelting wastes. The contents of metal oxides such as Fe, Mn, and Si were the influencing factors of PTEs enrichment. On the contrary, soil samples exhibited much lower Zn/Cd and Pb/Cd ratios in non-mining areas, indicating that the main origin of these metals in soil was the smelting flue gas dusts and geological background.