Morphological and functional alterations of hepatic mitochondria have been documented in patients with alcoholic liver disease (ALD). Our recent study demonstrated that zinc level was decreased in ...whole liver and mitochondria by chronic alcohol feeding. The present study was undertaken to determine whether zinc deficiency mediates alcohol-induced mitochondrial electron transport chain (ETC) defect and whether defective ETC function may lead to generation of reactive oxygen species (ROS). Male Wistar rats were pair fed with the Lieber-DeCarli control or ethanol diet for 5 mo. Chronic alcohol exposure increased hepatic triglyceride, free fatty acid, and 4-hydroxynonenal (4HNE) levels; meanwhile hepatic mitochondrial 4HNE level was also increased. Moreover, hepatic mitochondrial respiratory complexes I, III, IV, and V and hepatic ATP production were decreased by chronic alcohol exposure. Chronic alcohol feeding decreased peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PGC1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and mitochondrial DNA. HepG2 cells were treated with N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) for 6 h. Zinc deficiency significantly decreased mitochondrial respiratory complexes I, III, and IV. In addition, PGC1α, NRF1, and TFAM levels as well as mitochondrial DNA were significantly decreased by TPEN treatment. Knockdown of mitochondrial respiratory complexes I, III, or IV by shRNA caused a decrease in mitochondrial membrane potential and an increase in ROS production. These results suggest that alcohol-induced hepatic zinc deficiency could inactivate mitochondrial biogenesis pathway and decrease mitochondrial DNA replication, which, in turn, decreases mitochondrial complex protein expression. The defect of mitochondrial respiratory complexes may worsen alcohol-induced ROS production.
The earthquake‐induced displacement of sloping soil mass is an important indicator of co‐seismic landslide initiation. In this paper, an improved Newmark displacement model that considers the ...accumulation of dynamic pore water pressure (DPWP) in the soil caused by both vertical and horizontal ground motions is proposed. The model can quantitatively describe the dynamic changes of the seismic yield acceleration of near‐saturated infinite soil slopes. Three different types of ground motion time histories are selected to compare the performance of the proposed Newmark displacement model, and the influence of DPWP accumulation on the slope yield acceleration and on the seismic displacement is obtained. The seismic slope displacement analyses indicate that the weakening effect of slope yield acceleration caused by bidirectional earthquake excitation‐induced DPWP is more obvious than when only considering the horizontal ground motion, when the slip surface soils are in near‐saturated state. The effect of initial saturation (Sr0) on the DPWP accumulation caused by vertical ground motion is also investigated. Furthermore, the accumulated seismic displacement can be reasonably explained by the frequency distribution characteristics of the ground motions. Finally, the numerical results of this paper show that the seismic displacement model seldomly considering the effect of DPWP, or only considering the DPWP induced by horizontal ground motion, can significantly underestimate the displacement value when the slip surface soils are in a near‐saturated state.
Enterovirus 71 (EV71) is a highly transmissible pathogenic agent that causes severe central nervous system diseases in infected infants and young children. Here, we reported that EV71 VP1 protein ...could bind to vimentin intermediate filaments expressed on the host cell surface. Soluble vimentin or an antibody against vimentin could inhibit the binding of EV71 to host cells. Accompanied with the reduction of vimentin expression on the cell surface, the binding of EV71 to cells was remarkably decreased. Further evidence showed that the N terminus of vimentin is responsible for the interaction between EV71 and vimentin. These results indicated that vimentin on the host cell surface may serve as an attachment site that mediated the initial binding and subsequently increased the infectivity of EV71.
This study delivers important findings on the roles of vimentin filaments in relation to EV71 infection and provides information that not only improves our understanding of EV71 pathogenesis but also presents us with potentially new strategies for the treatment of diseases caused by EV71 infections.
The increase in the insecticide resistance of pests, such as
,
, and
, necessitates the development of new heterocyclic compounds with high insecticidal activity. A series of novel 2-phenylpyridine ...derivatives containing
-phenylbenzamide moieties were designed and synthesised with Suzuki-Miyaura cross-coupling, nucleophilic substitution, and amidation reactions. The reaction conditions in each step are mild, and the product is easy to separate (yield is about 85%). The structures of the compounds were characterised using
H and
C NMR spectroscopy and HRMS. Moreover, the insecticidal activity of the compounds was analysed using the leaf dipping method. The compounds
,
,
,
, and
at 500 mg/L exhibited 100% inhibition against
. Therefore, the 2-phenylpyridine moieties have the potential to lead to the discovery of novel and effective insecticides.
A
bstract
Taking into account that the real quantum materials are engineered generically at a finite chemical potential, we investigate the Einstein ring structure for the lensed response of the ...complex scalar field as a probe wave on the charged AdS black hole in the context of AdS/CFT. On the one hand, we find that the resulting Einstein ring radius has no variation with the chemical potential, which is similar to the behavior for the weakly interacting quantum system. On the other hand, not only can such a ring exist well within the screen, but also the temperature dependence of its radius exhibits a distinct feature in the sense that it displays an appreciable increase at low temperatures while the ring keeps unchanged right at the edge of the screen for the weakly interacting system. Note that such a Einstein ring emerges in the large frequencies and can be well captured by the photon sphere away from the black hole horizon in the geometric optics approximation, thus such a distinct feature may be regarded as a universal behavior associated with the high energy modes of the strongly coupled system which has a gravity dual.
To discover new compounds with favorable herbicidal activity, a range of phenylpyridine moiety-containing pyrazole derivatives were designed, synthesized, and identified via NMR and HRMS. Their ...herbicidal activities against six species of weeds were evaluated in a greenhouse via both pre- and post-emergence treatments at 150 g a.i./hm2. The bioassay revealed that a few compounds exhibited moderate herbicidal activities against Digitaria sanguinalis, Abutilon theophrasti, and Setaria viridis in post-emergence treatment. For instance, compounds 6a and 6c demonstrated 50% inhibition activity against Setaria viridis, which was slightly superior to pyroxasulfone. Thus, compounds 6a and 6c may serve as the new possible leading compounds for the discovery of post-emergence herbicides.
To discover novel herbicidal compounds with favorable activity, a range of phenylpyridine-moiety-containing α-trifluorothioanisole derivatives were designed, synthesized, and identified via NMR and ...HRMS. Preliminary screening of greenhouse-based herbicidal activity revealed that compound 5a exhibited >85% inhibitory activity against broadleaf weeds Amaranthus retroflexus, Abutilon theophrasti, and Eclipta prostrate at 37.5 g a.i./hm2, which was slightly superior to that of fomesafen. The current study suggests that compound 5a could be further optimized as an herbicide candidate to control various broadleaf weeds.
Background
Peroxisome proliferator‐activated receptor gamma (PPARγ) signaling has been shown to regulate lipogenesis and lipid accumulation. Previous studies have shown that hepatic PPARγ is ...up‐regulated in steatotic liver of both animal and human. However, the effects of hepatic PPARγ signaling on alcoholic liver disease (ALD) remain elusive.
Methods
To determine the role of hepatic PPARγ signaling on ALD, wild‐type (WT) and hepatocyte‐specific PPARγ knockdown (PPARγ∆Hep) mice were fed a modified Lieber‐DeCarli alcohol or isocaloric maltose dextrin control liquid diet for 8 weeks to induce ALD. Blood parameters, hepatic steatosis, and inflammation were measured after 8‐week alcohol feeding.
Results
Alcohol feeding to WT mice resulted in liver damage (alanine aminotransferase ALT, 94.68 ± 17.05 U/L; aspartate aminotransferase AST, 55.87 ± 11.29 U/L), which was significantly alleviated by hepatic PPARγ knockdown (ALT, 57.36 ± 14.98 U/L; AST, 38.06 ± 3.35 U/L). Alcohol feeding led to marked lipid accumulation and up‐regulation of lipogenic genes including fatty acid transport protein 1 (FATP1), acetyl‐CoA carboxylase (ACC), fatty acid synthase (FASN), lipin1 (LIPIN1), diacylglycerol acyltransferase 1 (DGAT1), and diacylglycerol acyltransferase 2 (DGAT2) in the livers of WT mice. Knockdown of hepatic PPARγ significantly alleviated alcohol‐induced lipid accumulation and abolished the up‐regulation of FASN, DGAT1, and DGAT2. Silencing of PPARγ in FL83B cells significantly decreased ethanol (EtOH)–, linoleic acid–, and EtOH plus linoleic acid–induced lipid accumulation. Knockdown of hepatic PPARγ also significantly reduced alcohol‐induced inflammatory chemokine (monocyte chemotactic protein 1 MCP1, keratinocyte‐derived chemokine KC, interferon gamma‐induced protein 10 IP‐10) and inflammatory infiltration (lymphocyte antigen 6 complex, locus G Ly6G, and F4/80).
Conclusions
The results suggest that hepatic PPARγ signaling contributes to alcohol‐induced liver injury by promoting hepatic steatosis and inflammation.
Hepatic PPARγ is upregulated by alcohol exposure in mice. Hepatocyte‐specific PPARγ knockdown alleviated alcohol‐induced liver damage through downregulation of lipid synthesis genes and inflammatory cytokine genes. Silencing of PPARγ in FL83B cells significantly decreased cellular lipid accumulation induced by ethanol, linoleic acid, or ethanol plus linoleic acid. The results suggest that hepatic PPARγ activation is a pathological factor in the development of alcoholic liver disease.
Although laparoscopic surgery has been available for a long time and laparoscopic cholecystectomy has been performed universally, it is still not clear whether open appendectomy (OA) or laparoscopic ...appendectomy (LA) is the most appropriate surgical approach to acute appendicitis. The purpose of this work is to compare the therapeutic effects and safety of laparoscopic and conventional "open" appendectomy by means of a meta-analysis.
A meta-analysis was performed of all randomized controlled trials published in English that compared LA and OA in adults and children between 1990 and 2009. Calculations were made of the effect sizes of: operating time, postoperative length of hospital stay, postoperative pain, return to normal activity, resumption of diet, complications rates, and conversion to open surgery. The effect sizes were then pooled by a fixed or random-effects model.
Forty-four randomized controlled trials with 5292 patients were included in the meta-analysis. Operating time was 12.35 min longer for LA (95% CI: 7.99 to 16.72, p < 0.00001). Hospital stay after LA was 0.60 days shorter (95% CI: -0.85 to -0.36, p < 0.00001). Patients returned to their normal activity 4.52 days earlier after LA (95% CI: -5.95 to -3.10, p < 0.00001), and resumed their diet 0.34 days earlier(95% CI: -0.46 to -0.21, p < 0.00001). Pain after LA on the first postoperative day was significantly less (p = 0.008). The overall conversion rate from LA to OA was 9.51%. With regard to the rate of complications, wound infection after LA was definitely reduced (OR = 0.45, 95% CI: 0.34 to 0.59, p < 0.00001), while postoperative ileus was not significantly reduced(OR = 0.91, 95% CI: 0.57 to 1.47, p = 0.71). However, intra-abdominal abscess (IAA), intraoperative bleeding and urinary tract infection (UIT) after LA, occurred slightly more frequently(OR = 1.56, 95% CI: 1.01 to 2.43, p = 0.05; OR = 1.56, 95% CI: 0.54 to 4.48, p = 0.41; OR = 1.76, 95% CI: 0.58 to 5.29, p = 0.32).
LA provides considerable benefits over OA, including a shorter length of hospital stay, less postoperative pain, earlier postoperative recovery, and a lower complication rate. Furthermore, over the study period it was obvious that there had been a trend toward fewer differences in operating time for the two procedures. Although LA was associated with a slight increase in the incidence of IAA, intraoperative bleeding and UIT, it is a safe procedure. It may be that the widespread use of LA is due to its better therapeutic effect.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential ...of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism. HODE-generating ALOX15 was up-regulated by chronic alcohol exposure. Linoleic acid, but not ethanol or acetaldehyde, induced ALOX15 expression in Hepa-1c1c7 cells. ALOX15 knockout prevented alcohol-induced liver damage via attenuation of oxidative stress, ER stress, lipid metabolic disorder, and cell death signaling. ALOX15 inhibitor (PD146176) treatment also significantly alleviated alcohol-induced oxidative stress, lipid accumulation and liver damage. These results demonstrated that activation of ALOX15/13-HODE circuit critically mediates the pathogenesis of ALD. This study suggests that ALOX15 is a potential molecular target for treatment of ALD.
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