Bismuth-rich bismuth oxyhalides (Bi–O–X; X = Cl, Br, I) display high photocatalytic reduction activity due to the promoting conduction band potential. In this work, two Bi5O7I nanosheets with ...different dominant facets were synthesized using either molecular precursor hydrolysis or calcination. Crystal structure characterizations, included X-ray diffraction patterns (XRD), field emission electron microscopy and fast Fourier transformation (FFT) images, showed that hydrolysis and calcination resulted in the dominant exposure of {100} and {001} facets, respectively. Photocatalytic data revealed that Bi5O7I–001 had a higher activity than Bi5O7I–100 for N2 fixation and dye degradation. Photoelectrochemical data revealed that Bi5O7I–001 had higher photoinduced carrier separation efficiency than Bi5O7I–100. The band structure analysis also used to explain the underlying photocatalytic mechanism based on the different conduction band position. This work presents the first report about the facet-dependent photocatalytic performance of bismuth-rich Bi–O–X photocatalysts.
Oscillospira is a common yet rarely cultivated gut bacterial genus. Recently human gut microbiota studies have demonstrated its underlying significance for host health. However, little is known about ...Oscillospira-related host information and the links between Oscillospira and other members of the gut microbial community. To study the ecology of Oscillospira and gain insights into Oscillospira-related host physiological conditions, we analyzed data from the Guangdong Gut Microbiome Project, one of the largest gut microbiota database currently. Data of 6376 participants were analyzed. We studied the prevalence and relative abundance of Oscillospira as well as the profiles of associated microbial communities. We found that Oscillospira is closely related to human health because its abundance was positively correlated with microbial diversity, high density lipoprotein, and sleep time, and was inversely correlated with diastolic blood pressure, systolic blood pressure, fasting blood glucose, triglyceride, uric acid and Bristol stool type. Moreover, random forest analysis with five-fold cross validation showed Oscillospira could be a predictor of low BMI and constipation in the subset. Overall, in this study, we provide a basic understanding of Oscillospira-related microbiota profile and physiological parameters of the host. Our results indicate Oscillospira may play a role in aggravating constipation.
OBJECTIVE—Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene ...expression, but their role in vascular precursor cell–mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow–derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice.
APPROACH AND RESULTS—BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66 and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66, and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice.
CONCLUSIONS—miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice.
Impaired angiogenesis and its induced refractory wound lesions are common complications of diabetes. Hydrogen sulfide (H2S) has been reported to have proangiogenic effects. We hypothesize that H2S ...improves diabetic wound healing by restoring endothelial progenitor cell (EPC) function in type 2 diabetes. db/db Mice were treated with sodium hydrosulfide (NaHS), 4-hydro-xythiobenzamide group (HTB), or saline for 18 days. db/+ Mice were treated with dl-propargylglycine (PAG) or saline for 18 days. Plasma H2S levels were significantly decreased in db/db mice and restored in the NaHS and HTB mice compared with the diabetic control group. Wound-closure rates were significantly faster in the NaHS and HTB groups than in the db/db group, in which the PAG group had slower wound-closure rates. Wound skin capillary densities were enhanced in the NaHS and HTB groups. EPC functions were significantly preserved in the NaHS and HTB groups but were decreased in the PAG group. Meanwhile, EPC functions of the db/+ mice were significantly reduced after in vitro PAG treatment or cystathionine-γ-lyase (CSE) silencing; EPC functions of db/db mice were significantly improved after in vitro NaHS treatment. The expressions of Ang-1 in wound skin tissue and in EPCs were upregulated in the NaHS and HTB groups compared with db/db controls, but were downregulated by in vivo PAG and in vitro siCSE treatment compared with normal controls. Diabetic EPC tube formation capacity was significantly inhibited by Ang-1 small interfering RNA before NaHS treatment compared with db/db EPCs treated with NaHS only. Taken together, these results show that H2S improves wound healing by restoration of EPC functions and activation of Ang-1 in type 2 diabetic mice.
•Urbanization level in BTHUA presented an increasing trend from 2000 to 2018.•Overall, ESV increased first then decreased.•CCD showed the trend of ‘high in the middle and low in the north and south, ...high in east and low in west’.•CCD at the subsystem scale presented a more coordinated trend.•Soil conservation and food production functions are urgent concerns in the future.
Urbanization has an important impact on the regional ecological security pattern, and clarifying the relationship between urbanization and ecosystem services can provide a reference for the regional high-quality sustainable development. Under the background of global economic integration, urban agglomerations have become the main driving force leading economy development in the world. As one of the three major urban agglomerations in China, the Beijing-Tianjin-Hebei urban agglomeration (BTHUA) plays an irreplaceable role in China's social and economic development. This study employed the coupling coordination degree (CCD) model to explore the change characteristics between the two integrated systems and subsystems of urbanization and ecosystem service value (ESV). Results showed that, from 2000 to 2018, the urbanization level of BTHUA has gradually increased, with change trend from the early state dominated by population and land urbanization to the state dominated by population and economic urbanization; the total ecosystem service value (TESV) and per ecosystem service value (PESV) of Chengde were higher than other cities such as Beijing obviously. CCD of urbanization and ESV in BTHUA showed the trend of ‘high in the middle and low on both sides in the north–south direction, high in east and low in west in east–west direction’, and the CCD at the subsystem scale presented a more coordinated trend. However, there is a gradual degradation of some functions of ecosystem services, and soil conservation and food production functions are urgent concerns in the future.
The efficacy of therapeutics is dependent on a drug binding to its cognate target. Optimization of target engagement by drugs in cells is often challenging, because drug binding cannot be monitored ...inside cells. We have developed a method for evaluating drug binding to target proteins in cells and tissue samples. This cellular thermal shift assay (CETSA) is based on the biophysical principle of ligand-induced thermal stabilization of target proteins. Using this assay, we validated drug binding for a set of important clinical targets and monitored processes of drug transport and activation, off-target effects and drug resistance in cancer cell lines, as well as drug distribution in tissues. CETSA is likely to become a valuable tool for the validation and optimization of drug target engagement.
Natural Products as a Source for Antifibrosis Therapy Chen, Dan-Qian; Feng, Ya-Long; Cao, Gang ...
Trends in pharmacological sciences (Regular ed.),
November 2018, 2018-11-00, 20181101, Letnik:
39, Številka:
11
Journal Article
Recenzirano
Although fibrosis is a final pathological feature of many chronic diseases, few interventions are available that specifically target the pathogenesis of fibrosis. Natural products are becoming ...increasingly recognized as effective therapies for fibrosis. The highlights of common cellular and molecular mechanisms of fibrosis facilitate the discovery of effective antifibrotic drugs. We describe some new profibrotic mechanisms and corresponding therapeutic targets using natural products. Interleukin, ephrin-B2, Gas6/TAM, Wnt/β-catenin, hedgehog pathway, PPARγ, lysophosphatidic acid, and CTGF are promising therapeutic targets. Natural products can target these mediators and inhibit chronic inflammation, myofibroblast activation, epithelial–mesenchymal transition, and extracellular matrix accumulation to alleviate fibrosis. Of note, natural products have the potential to inhibit fibrosis in one organ, simultaneously targeting fibrosis in multiple other organs, which provides us new strategies to find antifibrotic drugs.
Fibrosis is a final pathological feature of many chronic diseases and available interventions specifically targeting the pathogenesis of fibrosis are lacking; natural products can solve this issue.
Fibrosis develops from chronic inflammation, myofibroblast activation to EMT, and ECM accumulation, all of which can be blocked by natural products.
The investigation of the pathogenesis of fibrosis indicates that interleukin, Gas6/TAM, Wnt/β-catenin, hedgehog pathway, ephrin-B2, PPARγ, lysophosphatidic acid, and CTGF are promising therapeutic targets. Natural products can target these mediators or pathways to alleviate fibrosis.
Natural products have the potential to inhibit fibrosis in one organ, simultaneously targeting fibrosis in multiple other organs, which provide us new strategies to find antifibrotic drugs.
The lack of well-designed randomized, placebo-controlled clinical trials and safety hinder the development and application of natural products against fibrosis in clinics.
Dysbiosis of the gut microbiome and related metabolites in chronic kidney disease (CKD) have been intimately associated with the prevalence of cardiovascular diseases. Unfortunately, thus far, there ...is a paucity of sufficient knowledge of gut microbiome and related metabolites on CKD progression partly due to the severely limited investigations. Using a 5/6 nephrectomized (NX) rat model, we carried out 16S rRNA sequence and untargeted metabolomic analyses to explore the relationship between colon’s microbiota and serum metabolites. Marked decline in microbial diversity and richness was accompanied by significant changes in 291 serum metabolites, which were mediated by altered enzymatic activities and dysregulations of lipids, amino acids, bile acids and polyamines metabolisms. Interestingly, CCr was directly associated with some microbial genera and polyamine metabolism. However, SBP was directly related to certain microbial genera and glycine-conjugated metabolites in CKD rats. Administration of poricoic acid A (PAA) and
Poria cocos
(PC) ameliorated microbial dysbiosis as well as attenuated hypertension and renal fibrosis. In addition, treatments with PAA and PC lowered serum levels of microbial-derived products including glycine-conjugated compounds and polyamine metabolites. Collectively, the present study confirmed the CKD-associated gut microbial dysbiosis and identified a novel dietary and therapeutic strategy to improve the gut microbial dysbiosis and the associated metabolomic disorders and retarded the progression of kidney disease in the rat model of CKD.
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•Micro-mesoporous UiO-66 was synthesized with P123 as structure-directing agent.•Micro-mesoporous UiO-66 shows 2.6 times toluene adsorption capacity of UiO-66.•Micro-mesoporous ...structure improves the mass transfer rate and adsorption capacity.•Efficient regeneration of exhausted adsorbent was achieved by heating.
In this work, micro-mesoporous UiO-66 was successfully prepared with P123 (EO20PO70EO20) as structure-directing agent by a simple solvothermal method. Adsorption/desorption kinetics of gaseous toluene over pristine UiO-66 and micro-mesoporous UiO-66 were investigated by breakthrough experiments, toluene vapor adsorption isotherm measurements and temperature programmed desorption (TPD) experiments. The interactions between toluene and UiO-66 samples were assessed through the Henry’s law constant (KH) and the isosteric adsorption heat (ΔHads). The micro-mesoporous UiO-66 crystal demonstrated 2.6 times toluene adsorption capacity of the pristine UiO-66 when the P123/Zr4+ molar ratio was 0.2. Results showed that micropore adsorption was the main adsorption process and the larger pores in micro-mesoporous UiO-66 increased molecular diffusion rate and reduced the mass transfer resistance. This result indicated that micro-mesoporous structures and defect sites had a positive effect on toluene molecules capture. The breakthrough times and the working capacities decreased with the increase of the relative humidity and adsorption temperature. A good thermal stability and reproducibility were revealed over the micro-mesoporous UiO-66 in this paper.
The transmembrane protein 33 (TMEM33) was originally identified as an endoplasmic reticulum (ER) protein that influences the tubular structure of the ER and modulates intracellular calcium ...homeostasis. However, the role of TMEM33 in antiviral immunity in vertebrates has not been elucidated. In this article, we demonstrate that zebrafish TMEM33 is a negative regulator of virus-triggered interferon (IFN) induction via two mechanisms: mitochondrial antiviral signaling protein (MAVS) ubiquitination and a decrease in the kinase activity of TANK binding kinase 1 (TBK1). Upon stimulation with viral components, tmem33 was remarkably upregulated in the zebrafish liver cell line. The IFNφ1 promoter (IFNφ1pro) activity and mRNA level induced by retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) were significantly inhibited by TMEM33. Knockdown of TMEM33 increased host ifn transcription. Subsequently, we found that TMEM33 was colocalized in the ER and interacted with the RLR cascades, whereas MAVS was degraded by TMEM33 during the K48-linked ubiquitination. On the other hand, TMEM33 reduced the phosphorylation of mediator of IFN regulatory factor 3 (IRF3) activation (MITA)/IRF3 by acting as a decoy substrate of TBK1, which was also phosphorylated. A functional domain assay revealed that the N-terminal transmembrane domain 1 (TM1) and TM2 regions of TMEM33 were necessary for IFN suppression. Finally, TMEM33 significantly attenuated the host cellular antiviral capacity by blocking the IFN response. Taken together, our findings provide insight into the different mechanisms employed by TMEM33 in cellular IFN-mediated antiviral process.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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