ABSTRACT
Herein, we employed linear-response time-dependent functional theory nonadiabatic dynamic simulations to explore the photoinduced exciton dynamics of a chiral single-walled carbon nanotube CNT(6,5) covalently doped with a 4-nitrobenzyl group (CNT65-NO2). The results indicate that the introduction of a sp3 defect leads to the splitting of the degenerate VBM/VBM-1 and CBM/CBM+1 states. Both the VBM upshift and the CBM downshift are responsible for the experimentally observed redshifted E11* trapping state. The simulations reveal that the photoinduced exciton relaxation dynamics completes within 500 fs, which is consistent with the experimental work. On the other hand, we also conducted the nonadiabatic carrier (electron and hole) dynamic simulations, which completely ignore the excitonic effects. The comparison demonstrates that excitonic effects are indispensable. Deep analyses show that such effects induce several dark states, which play an important role in regulating the photoinduced dynamics of CNT65-NO2. The present work demonstrates the importance of including excitonic effects in simulating photoinduced processes of carbon nanotubes. In addition, it not only rationalizes previous experiments but also provides valuable insights that will help in the future rational design of novel covalently doped carbon nanotubes with superior photoluminescent properties.
ABSTRACT
BACKGROUND: Liver fibrogenesis is orchestrated by the paracrine signaling interaction between several resident cell types regulating the activation of hepatic stellate cells (HSCs). However, the molecular mechanisms underlying paracrine regulation are largely unknown. The aim of this study is to elucidate the role of Ninjurin2 in the crosstalk between hepatocytes and HSCs and better understand the implications of Ninjurin2 in liver fibrosis. METHODS: Ninj2 knockout mice (Ninj2-/-) and hepatocyte-specific Ninj2 overexpression mice (Ninj2Hep-tg) were constructed and followed by the induction of liver fibrosis using methionine- and choline-deficient (MCD) diet. The relationship between Ninjurin2 and liver fibrosis phenotype was evaluated in vivo by measurement of fibrotic markers and related genes. We used an in vitro transwell cell co-culture model to examine the impact of Ninjurin2 in hepatocytes on the crosstalk to HSCs. The interaction of Ninjurin2 and IGF1R and the regulation of PI3K-AKT-EGR1 were analyzed in vivo and in vitro. Finally, an inhibitory Ninjurin2 peptide was injected intravenously via the tail vein to investigate whether inhibiting of Ninjurin2 cascade can attenuate MCD diet-induced liver fibrosis in mice. RESULTS: We found that hepatic Ninjurin2 expression was significantly increased in fibrotic human liver and MCD diet-induced liver injury mouse models. In the mouse model, hepatocyte-specific overexpression of Ninj2 exacerbates MCD-induced liver fibrosis, while global Ninj2 knockout reverses the phenotype. To mimic hepatocyte-HSC crosstalk during liver fibrosis, we used co-culture systems containing hepatocytes and HSCs and determined that Ninjurin2 overexpression in hepatocytes directly activates HSCs in vitro. Mechanistically, Ninjurin2 directly interacts with insulin-like growth factor 1 receptor (IGF1R) and increases the hepatocyte secretion of the fibrogenic cytokine, platelet-derived growth factor-BB (PDGF-BB) through IGF1R-PI3K-AKT-EGR1 cascade. Inhibition of PDGFRB signaling in HSCs can abolish the profibrogenic effect of Ninjurin2. In addition, we demonstrated that a specific inhibitory Ninjurin2 peptide containing an N-terminal adhesion motif mitigates liver fibrosis and improves hepatic function in the mouse models by negatively regulating the sensitivity of IGF1R to IGF1 in hepatocytes. CONCLUSION: Hepatic Ninjurin2 plays a key role in liver fibrosis through paracrine regulation of PDGF-BB/PDGFRB signaling in HSCs, and the results suggesting Ninjurin2 may be a potential therapeutic target.
Subject(s)
Cell Adhesion Molecules, Neuronal , Hepatic Stellate Cells , Liver , Signal Transduction , Animals , Humans , Mice , Becaplermin/metabolism , Becaplermin/pharmacology , Becaplermin/therapeutic use , Cell Adhesion Molecules, Neuronal/metabolism , Cell Adhesion Molecules, Neuronal/pharmacology , Cell Adhesion Molecules, Neuronal/therapeutic use , Disease Models, Animal , Early Growth Response Protein 1/genetics , Early Growth Response Protein 1/metabolism , Early Growth Response Protein 1/pharmacology , Hepatic Stellate Cells/metabolism , Hepatocytes/metabolism , Liver/pathology , Liver Cirrhosis/metabolism , FibrosisABSTRACT
The sodium voltage-gated channel beta subunit 3 (SCN3B) plays a crucial role in electrically excitable cells and conduction tissue in the heart. Some previous studies have established that genetic modification in sodium voltage-channel genes encoding for the cardiac ß-subunits, such as SCN1B, SCN2B, SCN3B and SCN4B, can result in atrial fibrillation (AF). In the current study, we identified two rare variants in 5'UTR (NM_018400.4: c.-324C>A, rs976125894 and NM_018400.4: c.-303C>T, rs1284768362) of SCN3B in two unrelated lone AF patients. Our further functional studies discovered that one of them, the A allele of c.-324C>A (rs976125894), can improve transcriptional activity and may raise SCN3B expression levels. The A allele of c.-324C>A (rs976125894) has higher transcriptional activity when it interacts with GATA4, as we confirmed transcription factor GATA4 is a regulator of SCN3B. To the best of our knowledge, the current study is the first to demonstrate that the gain-of-function mutation of SCN3B can produce AF and the first to link a mutation occurring in the non-coding 5'UTR region of SCN3B to lone AF. The work also offers empirical proof that GATA4 is a critical regulator of SCN3B gene regulation. Our findings may serve as an encyclopedia for AF susceptibility variants and can also provide insight into the investigation of the functional mechanisms behind AF variants discovered by genetic methods.
ABSTRACT
In this study, a two-step functionalizing strategy by combining co-condensation with grafting procedures was employed to synthesize well-ordered Amino- and Thiol-Bifunctionalized SBA-15 (ATBS) mesoporous silica. Its physicochemical properties, performance, and mechanisms in immobilization of toxic metals Pb and Cd in water and soil were investigated. After bi-functionalization, X-ray diffractometer, transmission electron microscope, and N2 adsorption-desorption measurements confirmed that the ATBS maintained a highly-ordered mesoporous structure, large surface area and pore volume. The elemental analysis, Fourier transform infrared spectroscopy and X-ray Photoelectron Spectroscopy (XPS) evidenced the successful incorporation of amine and thiol groups into ATBS. These structure and functional characteristics of ATBS benefited Pb and Cd sorption. Sorption isotherms of Pb and Cd were better fit with Sips and Redlich-Peterson models. Sorption kinetics suggested that Pb sorption was mainly regulated by chemical reactions, whereas both diffusion process and chemical reactions were rate-regulating steps in Cd sorption. ATBS showed the maximum sorption capacities for Pb and Cd at 120 and 38 mg g-1, respectively. The sorption mechanisms revealed by XPS measurements suggested that Cd sorption was mainly attributed to thiol groups while Pb was efficiently bond to both thiol and amino groups. High and stable sorption efficiencies were attained in the pH range of 4-6, with a higher affinity towards Pb than Cd. Furthermore, its ability to immobilize Pb and Cd in soils was examined with an incubation experiment, which showed that ATBS reduced 30-56% of MgCl2-extractable Pb and Cd in a contaminated soil. The synthesized sorbent via the two-step functionalizing strategy shows high sorption efficiency towards Pb and Cd, and thus it has potential application in remediating Pb and Cd contaminated water and soils.
Subject(s)
Cadmium , Lead , Adsorption , Amines , Silicon Dioxide , Sulfhydryl CompoundsABSTRACT
Helicobacter pylori-induced oxidative stress plays an important role in gastric diseases. H. pylori disturbs gut microbiota. The objective is to investigate the effects of cranberry beverages on oxidative stress biomarkers and gut microbiota in H. pylori positive subjects. 171 H. pylori positive participants were randomly assigned to one of the three groups: high-dose (HCb; 480 mL cranberry beverage), low-dose (LCb; 240 mL cranberry beverage plus 240 mL placebo) and placebo (480 mL). Subjects consumed the beverages daily for 4 weeks. Fasting blood samples were analyzed for oxidative stress biomarkers. The intestinal microbiome was analyzed by 16S rRNA sequencing. Compared with the placebo, HCb resulted in a significantly higher increase of total antioxidant capacity (mean ± SD: 1.39 ± 1.69 IU mL-1vs. 0.34 ± 1.73 IU mL-1; p < 0.001) and a higher decrease of the lipid peroxidation product malondialdehyde (-7.29 ± 10.83 nmol mg-1vs. -0.84 ± 15.66 nmol mg-1; p = 0.025). A significant dose-dependent effect on the elevation of superoxide dismutase was observed (p < 0.001). Microbiome data showed that consuming HCb and LCb led to a significant reduction of Pseudomonas (p < 0.05). In conclusion, the current research showed that consuming cranberry beverages significantly improved the antioxidant status in H. pylori positive subjects, which may be related to the reshaping of gut microbiota.
Subject(s)
Gastrointestinal Microbiome/drug effects , Helicobacter Infections/diet therapy , Oxidative Stress/drug effects , Plant Preparations , Vaccinium macrocarpon , Adult , Double-Blind Method , Female , Fruit and Vegetable Juices , Helicobacter pylori , Humans , Male , Middle Aged , Plant Preparations/administration & dosage , Plant Preparations/pharmacologyABSTRACT
Arsenic (As) hyperaccumulator Pteris vittata is efficient in As uptake, translocation and accumulation, but the impacts of soil As concentrations on As accumulation and distribution in P. vittata are still unclear. The impacts of soil As (7.3, 63 and 228 mg kg-1) on plant growth and As accumulation in P. vittata after 6 months of growth were evaluated. Arsenic concentrations in the roots, midribs and pinna margin of P. vittata fronds of different maturity were determined by inductively coupled plasma mass spectrometry (ICP-MS) and scanning electron microscopy coupled with an energy dispersive spectrometer (SEM-EDS). While moderate As level at As63 didn't impact P. vittata growth, higher As at As228 decreased plant biomass by 38%. Under As stress, more As was accumulated in the senescing fronds (47%) and mature fronds (11%) than the young fronds. In senescing fronds, As concentrations in pinna margin were 2.3 times that of the midribs, consistent with As-induced necrotic symptom. Arsenic distribution based on SEM-EDS analysis revealed good correlation between Si and As in the pinnae (r = 0.49). Our data showed that As accumulation in pinna margin caused necrosis and Si may have a potential role in As detoxification in P. vittata.
Subject(s)
Pteris , Arsenic , Biodegradation, Environmental , Plant Roots , Soil , Soil PollutantsABSTRACT
Atrophy gastritis harbor a high risk for the development of dysplasia and gastric cancer. The study investigated the relationships of specific dietary patterns and endoscopic gastric mucosal atrophy. In this cross-sectional study, we enrolled 574 consecutive outpatients who were diagnosed as chronic gastritis according to endoscopic examination. Dietary intakes of study individuals was assessed using the semi-quantitative food group frequency questionnaire. Logistic regression analyses were used to evaluate the relationship between dietary patterns and endoscopic gastric mucosal atrophy adjusted for potential confounders. A total of 574 participants were included, 286 with endoscopic gastric mucosal atrophy. Three dietary patterns were identified by factor analysis. "Alcohol and fish" (tertile 1 vs. tertile 3: adjusted odds ratio = 1.85, 95% confidence interval: 1.06-3.22) and "coarse cereals" (tertile 1 vs. tertile 3: adjusted odds ratio = 2.05, 95% confidence interval: 1.24-3.39) were associated with an increased risk for endoscopic gastric mucosal atrophy but a "traditional" pattern was not. Dietary pattern was not associated with gastric mucosal atrophy in women or in participants with H. pylori infection. A high adherence to both "Alcohol and Fish" and "Coarse cereals" dietary patterns seem to be associated with higher odds of endoscopic gastric mucosal atrophy in men and in patients without H. pylori infection. Further prospective cohort studies needed to confirm these findings.
Subject(s)
Asian People , Feeding Behavior , Gastric Mucosa/diagnostic imaging , Gastric Mucosa/pathology , Gastroscopy , Adolescent , Adult , Atrophy , Female , Food , Humans , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Principal Component Analysis , Young AdultABSTRACT
Microbial arsenic transformation is important in As biogeochemical cycles in the environment. In this study, a new As-resistant bacterial strain Leclercia adecarboxylata As3-1 was isolated and its associated mechanisms in As resistance and detoxification were evaluated based on genome sequencing and gene annotations. After subjecting strain As3-1 to medium containing arsenate (AsV), AsV reduction occurred and an AsV-enhanced bacterial growth was observed. Strain As3-1 lacked arsenite (AsIII) oxidation ability and displayed lower AsIII resistance than AsV, probably due to its higher AsIII accumulation. Polymerase chain reaction and phylogenetic analysis showed that strain As3-1 harbored a typical AsV reductase gene (arsC) on the plasmids. Genome sequencing and gene annotations identified four operons phoUpstBACS, arsHRBC, arsCRDABC and ttrRSBCA, with 8 additional genes outside the operons that might have involved in As resistance and detoxification in strain As3-1. These included 5 arsC genes explaining why strain As3-1 tolerated high AsV concentrations. Besides ArsC, TtrB, TtrC and TtrA proteins could also be involved in AsV reduction and consequent energy acquisition for bacterial growth. Our data provided a new example of diverse As-regulating systems and AsV-enhanced growth without ArrA in bacteria. The information helps to understand the role of As in selecting microbial systems that can transform and utilize As.
Subject(s)
Arsenic/metabolism , Enterobacteriaceae/physiology , Environmental Pollutants/metabolism , Adaptation, Physiological , Bacterial Proteins/genetics , Enterobacteriaceae/genetics , GenomicsABSTRACT
Concomitant functional dyspepsia (FD) and psychosocial stressors have been reported; however, the association between FD and depression remains controversial and no quantitative meta-analysis exists. Published articles were identified through a comprehensive review of PubMed, Embase, and Web of Science from inception to the 8 July 2018. The pooled odds ratios (ORs) with 95% confidence intervals and subgroup analyses were calculated using a random-effects model. Findings for a total of 59 029 individuals were pooled across 23 studies and examined. Our analyses showed a positive association between FD and depression, with an OR of 2.28 (95% confidence interval: 2.02-3.81; I=100%). In the subgroup analysis, FD patients in Europe (OR=6.19) were more likely to have depression compared with Asians (OR=2.47); the overall significance results decreased the most in subgroup which the overall significance of the subgroup analyses results decreased the most in studies that adjusted for BMI (OR=1.42). Our meta-analysis showed a positive association between FD and depression. Further large-scale prospective cohort studies are needed to investigate the causality between FD and depression.
Subject(s)
Depression/etiology , Dyspepsia/complications , Observational Studies as Topic , Depression/epidemiology , Depression/psychology , Dyspepsia/epidemiology , Dyspepsia/psychology , Global Health , Humans , Morbidity/trendsABSTRACT
Arsenate (AsV) reduction in bacteria is essential to alleviate their arsenic (As) toxicity. We isolated a Bacillus strain PVR-YHB1-1 from the roots of As-hyperaccumulator Pteris vittata. The strain was efficient in reducing AsV to arsenite (AsIII), but the associated mechanisms were unclear. Here, we investigated its As resistance and reduction behaviors and associated genes at genome level. Results showed that the strain tolerated up to 20â¯mM AsV. When grown in 1â¯mM AsV, 96% AsV was reduced to AsIII in 48â¯h, with its AsV reduction ability being positively correlated to bacterial biomass. Two ars operons arsRacr3arsCDA and arsRKacr3arsC for As metabolisms were identified based on draft genome sequencing and gene annotations. Our data suggested that both operons might have attributed to efficient As resistance and AsV reduction in PVR-YHB1-1, providing clues to better understand As transformation in bacteria and their roles in As transformation in the environment.
Subject(s)
Arsenates/chemistry , Arsenic/chemistry , Bacillus/metabolism , Genome/genetics , Arsenates/analysisABSTRACT
Arsenic (As)-resistant bacteria are abundant in the rhizosphere and tissues of As-hyperaccumulator Pteris vittata. However, little is known about their roles in As transformation and As uptake in P. vittata. In this study, the impacts of P. vittata tissue extracts with or without surface sterilization on As transformation in solutions containing 100 µg L-1 AsIII or AsV were investigated. After 48 h incubation, the sterilized and unsterilized root extracts resulted in 45% and 73% oxidation of AsIII, indicating a role of both rhizobacteria and endobacteria. In contrast, AsV reduction was only found in rhizome and frond extracts at 3.7-24% of AsV. A total of 37 strains were isolated from the tissue extracts, which are classified into 18 species based on morphology and 16S rRNA. Phylogenic analysis showed that â¼44% isolates were Firmicutes and others were Proteobacteria except for one strain belonging to Bacteroidetes. While most endobacteria were Firmicutes, most rhizobacteria were Proteobacteria. All isolated bacteria belonged to AsV reducers except for an As-sensitive strain and one AsIII- oxidizer PVR-YHB6-1. Since As transformation was not observed in solutions after filtrating or boiling, we concluded that both rhizobacteria and endobacteria were involved in As transformation in the rhizosphere and tissues of P. vittata.
Subject(s)
Arsenic/metabolism , Firmicutes/isolation & purification , Proteobacteria/isolation & purification , Pteris/microbiology , Rhizosphere , Soil Pollutants/metabolism , Arsenates/metabolism , Arsenites/metabolism , Biodegradation, Environmental , Biotransformation , Oxidation-Reduction , Phylogeny , Pteris/metabolism , RNA, Ribosomal, 16S/geneticsABSTRACT
Arsenic (As) is a toxic carcinogen so it is crucial to decrease As accumulation in crops to reduce its risk to human health. Arsenite (AsIII) antiporter ACR3 protein is critical for As metabolism in organisms, but it is lost in flowering plants. Here, a novel ACR3 gene from As-hyperaccumulator Pteris vittata, PvACR3;1, was cloned and expressed in Saccharomyces cerevisiae (yeast), Arabidopsis thaliana (model plant), and Nicotiana tabacum (tobacco). Yeast experiments showed that PvACR3;1 functioned as an AsIII-antiporter to mediate AsIII efflux to an external medium. At 5 µM AsIII, PvACR3;1 transgenic Arabidopsis accumulated 14-29% higher As in the roots and 55-61% lower As in the shoots compared to WT control, showing lower As translocation. Besides, transgenic tobacco under 5 µM AsIII or AsV also showed similar results, indicating that expressing PvACR3;1 gene increased As retention in plant roots. Moreover, observation of PvACR3;1-green fluorescent protein fusions in transgenic Arabidopsis showed that PvACR3;1 protein localized to the vacuolar membrane, indicating that PvACR3;1 mediated AsIII sequestration into vacuoles, consistent with increased root As. In addition, soil experiments showed â¼22% lower As in the shoots of transgenic tobacco than control. Thus, our study provides a potential strategy to limit As accumulation in plant shoots, representing the first report to decrease As translocation by sequestrating AsIII into vacuoles, shedding light on engineering low-As crops to improve food safety.