Background & Aims Due to its anatomic connection, the liver is constantly exposed to gut-derived bacterial products or metabolites. Disruption of gut homeostasis is associated with many human ...diseases. The aim of this study was to determine the role of gut homeostasis in initiation and progression of hepatocellular carcinoma (HCC). Methods Disruption of intestinal homeostasis by penicillin or dextran sulfate sodium (DSS) and its restoration by probiotics were applied in a diethylnitrosamine (DEN) model of rat hepatocarcinogenesis. Results Patients with liver cirrhosis and HCC had significantly increased serum endotoxin levels. Chronic DEN treatment of rats was associated with an imbalance of subpopulations of the gut microflora including a significant suppression of Lactobacillus species, Bifidobacterium species and Enterococcus species as well as intestinal inflammation. Induction of enteric dysbacteriosis or intestinal inflammation by penicillin or DSS, respectively, significantly promoted tumor formation. Administration of probiotics dramatically mitigated enteric dysbacteriosis, ameliorated intestinal inflammation, and most importantly, decreased liver tumor growth and multiplicity. Interestingly, probiotics not only inhibited the translocation of endotoxin, which bears pathogen-associated molecular patterns (PAMPs) but also the activation of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1). As a result, the production of pro- and anti-inflammatory cytokines was skewed in favor of a reduced tumorigenic inflammation in the liver. Conclusions The data highlights the importance of gut homeostasis in the pathogenesis of HCC. Modulation of the gut microbiota by probiotics may represent a new avenue for therapeutic intervention to treat or prevent HCC development.
The microorganisms and natural organic matters (NOM) in the water significantly threaten the health of human being, thus, it is an emerging demand for removal of those pollutes via the cost-efficient ...ultrafiltration technique. Non-solvent induced phase separation (NIPS) is the most frequently employed method for preparing ultrafiltration membrane in industry, however, the intrinsic weaknesses of porous polymeric membranes, e.g. weak mechanical property, foulants adsorption, and low-resistance to acidic/basic conditions, greatly hamper their applications. Thus, novel polymer materials are required to tackle the issues. In this study, we used a novel polymer, polysulfate (PSE) and adopted it for preparing ultrafiltration membrane via NIPS approach. The phase inversion process of the PSE casting membrane was comprehensively studied by choosing different solvents and water as coagulation bath. The top surface (TS) pore size of the resultant membranes was tailored by changing the solvent or tuning the polymer concentration, reaching as small as 10 nm with a porosity of 82.6 ± 0.9%. The ultrafiltration performance of the optimized membrane outperforms most of the polymeric membranes, which shows both high flux of 135.8 ± 10.7 LMH and rejection efficiency of 99.1 ± 0.83% for 100 ppm HA aqueous solution. Furthermore, the prepared membrane also owns antifouling and acid/alkaline-resistance characters, which endow the PSE membrane with great promise in the future industrially ultrafiltration applications.
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•Novel porous polysulfate membranes were prepared via NIPS approach.•Process kinetics predominantly control the membrane formation.•Tailored membrane surface pore size by the solvent or the polymer concentration.•A high flux of 135.8 LMH and rejection efficiency of 99.1% were achieved in removal of natural organic matter.•Excellent acid/alkaline-resistance capability.
A facile approach to fabricate fluorinated molecular monolayer on the surface of polydimethylsiloxane (PDMS) membrane was conducted using fluoroalkylsilane (FAS) as cross-linking agent. In detail, ...hydroxyl terminated PDMS were cross-linked with 1H,1H,2H,2H-Perfluorodecyltriethoxysilane and cast on porous polysulfone support to prepare PDMS membranes. X-ray photoelectron spectroscopy showed that fluorinated alkyl chains were enriched at the surface of the membranes. Moreover, the surface fluorine concentration increased with the increasing of FAS and plateaued at around 55at% (close to that of FAS molecules) when the surface was fully covered by fluorinated monolayers. The surface hydrophobicity was proportional to the surface fluorine content as revealed by water contact angle measurement. When applied in pervaporation separation of 1wt% n-butanol/water mixture at 60°C, the membrane prepared with a FAS ethoxy to PDMS hydroxyl equivalents ratio of 35 (PDMS-FAS-35) exhibited a flux of 843g−2h−1 and an enhanced permeate n-butanol concentration of 34.3wt% compared with PDMS cross-linked with traditional TEOS (1375g−2h−1, 24.4wt%). The decrease of permeate flux was because of the reduced water partial flux without sacrificing the butanol partial flux on the consequence of water repellency of FAS monolayer. The results indicated that the FAS cross-linked PDMS could increase the separation efficiency of the membrane, thereby reducing the cost and energy consumption of the pervaporation process.
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•Pervaporation membrane was prepared by polydimethylsiloxane and fluoroalkylsilane.•Tight fluorinated layer was formed on the surface of resultant membrane.•The fluorinated layer showed high hydrophobicity and water repellency.•Enhanced butanol selectivity in pervaporation recovery of n-butanol.•Energy consumption was decreased by reducing the water flux by half.
Small GTPases mediate transmembrane signaling and regulate the actin cytoskeleton in eukaryotic cells. Here, we characterize the auditory pathology of adult male CBA/J mice exposed to traumatic noise ...(2-20 kHz; 106 dB; 2 h). Loss of outer hair cells was evident 1 h after noise exposure in the basal region of the cochlea and spread apically with time, leading to permanent threshold shifts of 35, 60, and 65 dB at 8, 16, and 32 kHz. Several biochemical and molecular changes correlated temporally with the loss of cells. Immediately after exposure, the concentration of ATP decreased in cochlear tissue and reached a minimum after 1 h while the immunofluorescent signal for p-AMPKα significantly increased in sensory hair cells at that time. Levels of active Rac1 increased, whereas those of active RhoA decreased significantly 1 h after noise attaining a plateau at 1-3 h; the formation of a RhoA-p140mDia complex was consistent with an activation of Rho GTPase pathways. Also at 1-3 h after exposure, the caspase-independent cell death marker, Endo G, translocated to the nuclei of outer hair cells. Finally, experiments with the inner ear HEI-OC1 cell line demonstrated that the energy-depleting agent oligomycin enhanced both Rac1 activity and cell death. The sum of the results suggests that traumatic noise induces transient cellular ATP depletion and activates Rho GTPase pathways, leading to death of outer hair cells in the cochlea.
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Two-dimensional layered double hydroxides (LDH) as a membrane material has tremendous potential in the water treatment field. However, the stability and permeance of the LDH membrane ...should be further improved for the industrial application. In this study, the LDH separation layer was in situ grown on the tubular Al2O3 substrate. The obtained LDH composite membrane was then calcined to reduce the surface free energy and remove some interlayer anions. Therefore, the calcined LDH composite membrane exhibited enhanced stability and permeance for removing dye molecules from water. The permeance of the calcined LDH membrane reached 367Lm−2h−1MPa−1 and the rejection for Eriochrome black T was still above 99%. Moreover, the membrane can maintain the separation performance more than 110h in the nanofiltration process. The morphologies and structures of the LDH membranes before and after calcination were also investigated. The results indicated that this facile method is effective to improve the separation performance of the LDH membrane.
Organic light-emitting diodes (OLEDs) have been widely used in various fields such as sensors. In this article, we designed six novel heterocyclic Ir(III) complexes: (CFM)
2
Ir(acac) (named 1 in this ...paper), (TTIQ)
2
Ir(acac) (named 2), (CFM)
2
Ir(tmd) (named 3), (TTIQ)
2
Ir(tmd) (named 4), (CFM)
2
Ir(pic) (named 5) and (TTIQ)
2
Ir(pic) (named 6). The six iridium (III) complexes were calculated using Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT). We studied the bands of the lowest-lying absorptions and lowest energy emissions of complexes 1-6. In addition, we also explored their spectral properties, frontier Molecular Orbital theory(FMO) and spin-orbital coupling value(SOC). Where acac is represented as pentane-2, 4-dione; tmd as 2,2,6,6-tetramethylheptane-3,5-dione; pic as pyridine-2-carboxylate; TTIQ as 1-
thieno3,2-bthiophen-2-yl
isoquinoline; CFM as 2-(4-fluorobrobenyl)-4-methylpyridine.
A series of heteroleptic cyclometalated Ir (III) complexes, which are used for OLED application, were investigated by DFT and TD-DFT method. The frontier molecular orbital character and charge transfer character shown that they have the advantages of low efficiency roll-off properties, which is a 'stumbling block' in the process of OLED solid-lighting's development. Namely, means the materials will play an important role in the journey development of OLED.
Molecular sieve-based membranes are considered to be promising for achieving both high selectivity and permeability. Layered double hydroxides (LDHs) are typical two-dimensional crystalline compounds ...with highly uniform interlayer galleries that can be used to construct efficient molecular transport pathways. Herein, vertically channeled laminates are constructed on a tubular alumina substrate using CoAl–LDH as building blocks. Good-quality laminates are crystallized by direct nucleation and growth onto the alumina, in which alumina substrates act as both reactants and supports. Vertically aligned interlayer galleries are formed as sieving and transport channels for water molecules with the oriented nucleation effect of NH
4
F. Compared with the zigzag pathways formed by two dimensional materials parallel to the substrate, the straight vertical channels have higher molecular transfer efficiency. As a result, the robust CoAl–LDH membranes show much higher and more stable organic solvent dehydration performance than most membranes under a wide range of feed conditions. This work thus demonstrates that LDH-based composite membranes are highly promising as the next generation of membranes for molecular sieving.
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•4-octyl itaconate ameliorates acute respiratory distress syndrome via inhibiting LPS-mediated alveolar macrophage pyroptosis and inflammation.•4-octyl itaconate rescues LPS-induced ...mitochondrial dysfunction and cytosolic escape of mitochondrial DNA.•4-octyl itaconate suppresses the cGAS-STING-IRF3 pathway.•4-octyl itaconate exerts an anti-pyroptosis effect in a STING/IRF3-dependent manner.
Acute respiratory distress syndrome (ARDS) is a high-mortality pulmonary disorder characterized by an intense inflammatory response and a cytokine storm. As of yet, there is no proven effective therapy for ARDS. Itaconate, an immunomodulatory derivative accumulated during inflammatory macrophage activation, has attracted widespread attention for its potent anti-inflammatory and anti-oxidative properties. This study pointed to explore the protective impacts of 4-octyl itaconate (4-OI) on ARDS. The results showed that lung injury was attenuated markedly after 4-OI pre-treatment, as represented by decreased pulmonary edema, inflammatory cell infiltration, and production of inflammatory factors. LPS stimulation induced NLRP3-mediated pyroptosis in vitro and in vivo, as represented by the cleavage of gasdermin D (GSDMD), IL-18 and IL-1β release, and these changes could be prevented by 4-OI pretreatment. Mechanistically, 4-OI eliminated mitochondrial reactive oxygen species (mtROS) and mtDNA escaping to the cytosol through the opening mitochondrial permeability transition pore (mPTP) in alveolar macrophages (AMs) under oxidative stress. In addition, 4-OI pretreatment markedly downregulated cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) expression, and interferon regulatory factor 3 (IRF3) phosphorylation in vitro and in vivo. Meanwhile, inhibition of STING/IRF3 pathway alleviated NLRP3-mediated pyroptosis induced by LPS in vitro. Taken together, this study indicated that 4-OI ameliorated ARDS by rescuing mitochondrial dysfunction and inhibiting NLRP3-mediated macrophage pyroptosis in a STING/IRF3-dependent manner, which further revealed the potential mechanism of itaconate in preventing inflammatory diseases.
Background & Aims Accumulating evidence suggests the involvement of tumor-initiating cells (T-ICs) in cancer genesis, but whether liver T-ICs contribute to HCC invasion and metastasis remains ...unclear. Methods OV6+ T-ICs were isolated from SMMC7721 and HuH7 cell lines by magnetic sorting. Characteristics of T-ICs were assessed by in vitro and mouse xenograft assays. Expression of OV6 was determined by immunostaining in specimens from 218 HCC patients, and Kaplan–Meier survival analysis was used to determine the correlation of OV6 expression with prognosis. Results OV6+ T-ICs isolated from HCC cell lines not only possess a higher capacity to form tumor spheroids in vitro , but also had a greater potential to form tumors when implanted in non-obese diabetic/severe combined immunodeficient mice, suggesting their elevated self-renewal capacity and tumorigenicity. Moreover, OV6+ T-ICs exhibited more invasive and metastatic potentials both in vitro and in vivo . Patients with more OV6+ tumor cells were associated with aggressive clinicopathologic features and poor prognosis. CXCR4 is expressed at higher levels in OV6+ cells. Recombinant stromal cell-derived factor-1 (SDF-1) treatment expanded the OV6+ HCC T-ICs population, by sustaining the stem cell property of OV6+ cells. The SDF-1 effect was blocked by a specific CXCR4 inhibitor, AMD3100, or transfection of siRNA targeting CXCR4. Conclusions OV6+ HCC cells may represent a subpopulation of T-ICs with augmented invasion and metastasis potential, which contribute to progression and metastasis of HCC. The SDF-1/CXCR4 axis also provides therapeutic targets for elimination of liver T-ICs.
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