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31.
Lisa Goedtke Heike Sprenger Ute Hofmann Felix F. Schmidt Helen S. Hammer Ulrich M. Zanger Oliver Poetz Albrecht Seidel Albert Braeuning Stefanie Hessel-Pras 《International journal of molecular sciences》2021,22(1)
Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential. 相似文献
32.
Vicen Ruiz de Porras Juan Carlos Pardo Lucia Notario Olatz Etxaniz Albert Font 《International journal of molecular sciences》2021,22(9)
Since 2010, several treatment options have been available for men with metastatic castration-resistant prostate cancer (mCRPC), including immunotherapeutic agents, although the clinical benefit of these agents remains inconclusive in unselected mCRPC patients. In recent years, however, immunotherapy has re-emerged as a promising therapeutic option to stimulate antitumor immunity, particularly with the use of immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 and CTLA-4 inhibitors. There is increasing evidence that ICIs may be especially beneficial in specific subgroups of patients with high PD-L1 tumor expression, high tumor mutational burden, or tumors with high microsatellite instability/mismatch repair deficiency. If we are to improve the efficacy of ICIs, it is crucial to have a better understanding of the mechanisms of resistance to ICIs and to identify predictive biomarkers to determine which patients are most likely to benefit. This review focuses on the current status of ICIs for the treatment of mCRPC (either as monotherapy or in combination with other drugs), mechanisms of resistance, potential predictive biomarkers, and future challenges in the management of mCRPC. 相似文献
33.
Gang Li Dan I. Enache Jennifer Edwards Albert F. Carley David W. Knight Graham J. Hutchings 《Catalysis Letters》2006,110(1-2):7-13
The oxidation of benzyl alcohol to benzaldehyde has been investigated in the absence of solvent using zeolite-supported Au
and Au–Pd catalysts. Three zeolites were investigated, ZSM-5, zeolite β and zeolite Y, and these were contrasted with the
titanoslicalite TS-1 and TiO2 as supports. For the Au catalysts the best results are obtained with zeolite β as the support and the conversions were comparable
or better than those observed with TiO2 in terms of turn over frequencies. However, the selectivities observed with the acidic zeolites were lower than the non-acidic
TS-1 and TiO2. This is due to the subsequent reaction of benzaldehyde via acid catalysed reactions to give benzyl benzoate and its dibenzyl
acetal, and, in some cases dibenzylether. Initial catalysts were evaluated with a gold loading of 2 wt% and increasing this
to 4 wt% showed the expected increase in activity, indicating that there is scope to improve the performance of these catalysts.
The most active catalysts were prepared by impregnation and catalysts prepared by deposition precipitation were considerably
less active. Introduction of Pd into the catalyst improved the activity without significantly affecting the selectivity. 相似文献
34.
Saleh Al-Sayari Albert F. Carley Stuart H. Taylor Graham J. Hutchings 《Topics in Catalysis》2007,44(1-2):123-128
The preparation of Au/ZnO and Au/Fe2O3 catalysts using two coprecipitation methods is investigated to determine the important factors that control the synthesis
of high activity catalysts for the oxidation of carbon monoxide at ambient temperature. In particular, the factors involved
in the preparation of catalysts that are active without the need for a calcination step are evaluated. The two preparation
methods differ in the manner in which the pH is controlled during the precipitation, either constant pH throughout or variable
pH in which the pH is raised from an initial low value to a defined end point. Non-calcined Au/ZnO catalysts prepared using
both methods are very sensitive to pH and ageing time, and catalysts prepared at a maximum pH = 5 with a short ageing time
(ca. 0–3 h) exhibit high activity. Catalysts prepared at higher pH give lower activity. However, all catalysts require a short
operation period during which the oxidation activity increases. In contrast, the calcined catalysts are not particularly sensitive
to the preparation conditions. Non-calcined Au/Fe2O3 catalysts exhibit high activity when prepared at pH ≥ 5. Calcined Au/Fe2O3 prepared using the controlled pH method retain high activity, whereas calcined catalysts prepared using the variable pH method
are inactive. The study shows the immense sensitivity of the catalyst performance to the preparation methods. It is therefore
not surprising that marked differences in the performance of supported Au catalysts for CO oxidation that are apparent in
the extensive literature on this subject, particularly the effect of calcination, can be expected if the preparation parameters
are not carefully controlled and reported. 相似文献
35.
A study has been made of the cathodic deposition of copper ions from flowing dilute aqueous solutions onto a packed bed of graphite. The electrodeposition reaction is mass transfer controlled and expressions are presented for the cathodic current as a function of time, solution flow rate and bed characteristics. These have been verified from potentiostatic experiments. The cathode current efficiency is shown to approach 100% and packed bed electrodes are shown to be an effective means of extracting or removing metal ions from dilute solutions. 相似文献
36.
Soluble sugars are essential nutrients generally perceived as phagostimulants to most insects studied. However, tannins are known as digestibility reducers, hence deleterious to caterpillar development, and as deterrents as well. Previous work demonstrated that larvae of the polyphagous oblique-banded leafroller, Choristoneura rosaceana, performed better when reared on a control + 0.5% tannic acid diet than on the standard control diet and that larvae reared on a control + 5% glucose diet had slower development and reduced survival. This study was designed to elucidate the behavioral and neurophysiological components of the larval responses to tannic acid and glucose. C. rosaceana larvae were reared individually from the first to the sixth instar on one of four different artificial diets: (1) control; (2) control + 5% glucose; (3) control + 0.5% tannic acid; (4) control + 5% glucose + 0.5% tannic acid. After 14 days, larvae reared on the control + 5% glucose diet had not developed past the fourth instar, whereas a considerable proportion of larvae reared on the control + 0.5% tannic acid diet had already attained the pupal stage. Insects reared on the control or the control + 5% glucose + 0.5% tannic acid diet had intermediate development, with most larvae in the fifth instar. In addition, once the mid-sixth instar was reached, the feeding preferences to 25 and 300 mM glucose, 25 mM tannic acid, and 25 mM glucose + 25 mM tannic acid over water were assessed in two-choice tests. Feeding affected preference. Control-reared insects preferred feeding on treatments containing glucose and were not deterred by tannic acid. However, larvae that had been exposed to tannic acid during their development were deterred by tannic acid and their glucose discrimination was impaired. The sensitivity to glucose was also examined from neurophysiological recordings by stimulating the sugar-sensitive cell (cell 1) on the lateral styloconic sensillum of the maxillary galea with increasing concentrations of glucose (1, 10, 25, 50, 100, 200, 300, and 500 mM). We also determined whether tannic acid was phagostimulatory, since insects develop relatively quickly on a diet containing this compound, by testing 1 mM tannic acid, 1 mM tannic acid + 300 mM glucose, and 300 mM glucose on the lateral styloconic sensilla. The traces indicated that 1 mM tannic acid was not detected by any of the four chemosensory cells in these sensilla. The combination of tannic acid and glucose produced no spikes from the sugar-sensitive cell, whereas a prominent spike activity resulted with 300 mM glucose. We concluded that, although C. rosaceana larvae develop faster on a tannic acid diet, this compound is not a phagostimulant. The converse is true for glucose; i.e., it stimulates the sugar-sensitive cell in the lateral styloconica in a concentration-dependent fashion. Previous dietary experience changes the sensory and behavioral responses of C. rosaceana to glucose. Our findings imply that not all compounds that are phagostimulatory are necessarily beneficial to an insect's fitness. Therefore, developmental studies should be interpreted in conjunction with behavioral and physiological data. 相似文献
37.
We evaluated the effects of tannic acid and purified perrsimmon tannin on survival and reproduction of bean bugs, Riptortus clavatus.Feeding behavior of R. clavatus was also examined on sweet (cv. Fuyu) and astringent (cv. Chongdosi) persimmon fruits. Soluble tannin in sweet persimmon fruits decreased from 3% in early June to 0.5% in late September, but it increased from 2 to 8% during the same period in astringent persimmon fruits. More bugs visited sweet than astringent persimmon. Numbers of piercing/sucking spots were higher on sweet than on astringent persimmon. When fed 1 and 3% solutions of persimmon tannin, adult bugs ingested only 64.1 and 9.5% of the amount of water ingested by those offered the control (distilled water). Amounts of persimmon tannin ingested by the adult bugs were 6.5 and 2.8 times higher at 1 and 3% tannin solutions compared to a 0.1% solution. Persimmon tannin exerted negative effects on survival and reproduction of R. clavatus at higher concentrations (1 and 3% solutions). Feeding of R. clavatus adults decreased with increasing tannin concentrations. When results from both sexes were pooled, 50% mortality was achieved at 11 and 4 days after treatment with the 1 and 3% tannin solutions, respectively. Reproduction decreased with 1% tannin, and no eggs were produced with 3% tannin solution. Tannic acid was similar in its effects on R. clavatus. All nymphs died 14, 12, and 7 days after feeding on 0.1, 1, and 3% tannic acid, respectively. Adults were less sensitive than nymphs, and their survival was not affected by 0.1% tannic acid. However. 1 and 3% tannic acid solutions were fatal. Survivorship decreased to 50% at 11 and 6 days after supplying tannin solutions of 1 and 3% concentrations. Higher concentrations (1 and 3%) resulted in reduced reproduction, as was seen with persimmon tannin. Our data may explain why R. clavatus does not invade sweet persimmon orchards until late July, when concentrations of soluble tannin are low enough to allow them to feed. 相似文献
38.
The work reported here represents initial attempts to develop a complete kinetic and mechanistic understanding of the reaction chemistry of H2S under coal liquefaction conditions, using both model systems and coal. Hydrogen sulphide was found to promote/catalyse the transfer of hydrogen from tetralin to 2-hydroxyquinoline (2-HOQ). The presence of H2S can increase the rate of hydrogen transfer from tetralin to 2-HOQ by a factor of 10 compared with the same reaction run in the absence of H2S. The energy of activation for hydrogen transfer was found to decrease by ≈5 kcal mol−1 in the presence of H2S. The presence of H2S was also found to promote loss of oxygen from 2-HOQ to form small amounts of quinoline. No evidence of CC or CN bond cleavage in 2-HOQ was noted under any of the reaction conditions studied. These results suggest that the presence of H2S reduces the temperatures necessary to promote effective hydrogen transfer from tetralin by 50–75 °C. Moreover, they imply that similar effects occur in H2S-promoted coal liquefaction. 相似文献
39.
Albert W. Alexander Bodhisattwa Chaudhuri AbdulMobeen Faqih Clive Davies 《Powder Technology》2006,164(1):13-21
The flow dynamics of cohesive powders is investigated in rotating cylinders with an L : R ratio of 3 : 1 using experiments and DEM simulations. Flow onset and steady-state behavior are compared for free-flowing (cohesionless) dry glass beads, wet glass beads, and “dry” cohesive powders (lactose, microcrystalline cellulose). The avalanching dynamics of powders is substantially different from those observed for free-flowing or wet-cohesive glass beads. Dry cohesive powders exhibit history-dependent flow dynamics, significant dilation, aperiodic avalanche frequencies, and variable avalanche size. These behaviors also provide a route for effective characterization of cohesive forces under dilated conditions characteristic of unconfined flows. 相似文献
40.
We introduce a novel non-dimensional “intrinsic layer-line spacing” concept for electron diffraction analysis of single-walled carbon nanotubes (SWCNTs). Accordingly, we develop a unique method for direct determination of chiral indices (n, m) of the carbon nanotubes from their electron diffraction patterns (EDPs). The new method is totally calibration-free. Errors due to the nanotube inclination are specified. The tilt angle of the carbon nanotube with respect to the incident electron beam is simultaneously evaluated, thus the effect of the tube tilting is compensated for in the (n, m) determination. Several effective procedures are proposed to cross-check the results by using abundant information contained in the diffraction patterns. The efficiency of the method is demonstrated on both simulated and experimental diffraction patterns from single-walled nanotubes. The technique can be extended to structural analysis of nanotubes of structure similar to carbon nanotubes, such as boron nitride nanotubes. 相似文献