Safely and high-efficiently breaking rock is of practical significance. In some engineering, explosive blasting may be restricted for its side effects. Traditional non-explosive methods like ...demolition agent and rock breaking machine are generally time-consuming. Therefore, this study proposes a novel liquid carbon dioxide rock-breaking technology and designs the relative device. The effectiveness, safety and high-efficiency of the proposed technology are investigated by shock pressure test, vibration site test and field rock breaking experiment. The experimental results show that the duration of the monitoring shock pressure is around 1500 μs. The shock pressure signal of liquid carbon dioxide tube breaking in free condition contains four stages, namely, increasing exponentially, decreasing oscillatory, stabilization, and negative pressure stage. As pressure sensor is set at 850 mm from the test tube radially, the shock pressure monitored increases to the maximum value of 115.7 kPa within 6 μs. During the liquid carbon dioxide rock breaking, the vertical component of the peak particle velocity of vibration is 173 mm/s, 85 mm/s and 35 mm/s along distance at 1.5 m, 2.5 m and 3.5 m from the tube, respectively. The Fourier power spectra results show that about 85% energy distributes at 6–60 Hz. The vibration caused by the novel technology can meet the requirement of mainstream blasting safety criteria better than that of explosive blasting. Finally, the technology is successfully applied in rock excavation at a metro station construction site. The proposed liquid carbon dioxide rock-breaking technology is preliminarily demonstrated to be safer than explosive blasting and more efficient than traditional non-explosive techniques.
A convenient Fe-catalyzed four-component radical dual difunctionalization and ordered assembly of two alkenes with aromatic/aliphatic aldehydes and TBHP to provide chain elongated β,δ-functionalized ...ketones via a one-pot procedure has been developed. Aldehydes were homolytically cleavaged to produce acyl radicals and subsequently allowed for the successive construction of C(sp2)–C(sp3), C(sp3)–C(sp3), and C(sp3)–O bonds via dual radical insertions and radical–radical coupling, following the intrinsic nucleo/electrophilic reactivity of both the radicals and alkenes.
A practical zinc acetate dihydrate‐catalyzed reductive amination of various carbonyl compounds with N,N‐dimethylformamide (DMF) as dimethylamino (Me2N) source, reductant and solvent has been ...developed. This reaction shows broad substrate scope, good functional group tolerance, avoids the need for a pressure‐proof reactor and column chromatographic isolation operations and gives up to 98% yield, to make it an attractive method for the preparation of tertiary N,N‐dimethylamines.
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•A series of unique isothiazole-fused quinolinoquinone analogues were synthesized.•Some isothiazoloquinolinoquinones strongly inhibit proliferation of cancer cells and may induce ...cancer cells apoptosis.•Isothiazoloquinolinoquinones are efficient substrates for NQO1 and induce ROS production in vitro.•Isothiazoloquinolinoquinone inhibits the phosphorylation of STAT3.
Natural quinones and their analogues have attracted growing attention because of their novel anticancer activities. A series of novel isothiazoloquinoline quinone analogues were synthesized and evaluated for antitumor activities against four different kind of cancer cells. Among them, isothiazoloquinolinoquinones inhibited cancer cells proliferation effectively with IC50 values in the nanomolar range, and isothiazoloquinolinoquinone 13a induced the cell apoptosis. Further exploration of possible mechanism of action indicates that 13a not only activates ROS production through NQO1-directed redox cycling but also inhibits the phosphorylation of STAT3. These findings indicate that 13a has potential use for the development of new skeleton drug candidate as an efficient substrate of NQO1 and STAT3 inhibitor.
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•Twelve novel DLC (delocalized lipophilic cation) modified spinosyn derivatives were synthesized.•Greatly enhanced antiproliferative activities towards human cancer ...cells.•Lipophicility has a great influence on the antiproliferative effects of these derivatives.•Both the isoquinolinium derivative 7b and triphenylphosphinium derivative 8b exhibited remarkably enhanced OXPHOS inhibition and apoptosis inducing ability.•Both 7b and 8b exhibited a certain extent of in vivo antitumor effect.
A series of DLC (delocalized lipophilic cation) modified spinosyn derivatives were synthesized and evaluated for antitumor efficacies both in vitro and in vivo. Cancer cell based antiproliferative assays indicated that the more lipophilic derivatives had stronger inhibitory effects on the tested cancer cell lines. Compound 7b and 8b exhibited strong anti-OXPHOS and apoptosis inducing ability. Notable antitumor efficacies of 7b (5 mg/kg) and 8b (2.5 mg/kg) were observed in the in vivo tumor xenograft experiments, however, lethal toxicities were observed on higher dosages. Our findings indicated that DLC modification is a viable strategy to enhance the anti-OXPHOS and antitumor efficacies of spinosyn derivatives.
The heptaprotective flavonolignan silibinin and dehydrosilibinin have exhibited moderate antiproliferative activities toward many cancer cell lines. Considering of the nontoxic profile of these ...natural products, chemical modification to enhance the anticancer potentials is promising.
A series of 7-O-aminoalkyl-2,3-dehydrosilibinin derivatives were synthesized and evaluated for their antiproliferative activities against several cancer cell lines.
A number of the synthesized dehydrosilibinin derivatives exhibited greatly enhanced potency with 50% growth inhibition at low micromolar concentrations. Structure activity study indicated that the distance between N and 7-O on the side chain has a limited influence on the antiproliferative activity, while the presence of a morpholino group decreases the antiproliferative activities dramatically. Flow cytometry based assays on human colon cancer HCT116 cells revealed that 6a and 6c, two of the most potent derivatives, effectively arrested the cell cycle in the G2 phase and stimulated cell apoptosis.
Our findings suggest that attaching an appropriate tertiary amino alkyl side chain through 7-Oalkylation on 2,3-dehydrosilibinin, would be a viable strategy for the development of silibinin derivatives as anticancer agents.
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•Thirteen novel quartenary ammonium spinosyn derivatives were synthesized.•Greatly enhanced antiproliferative activities.•Lipophicility has a great influence on the antiproliferative ...effects of these derivatives.•Compound 11d exhibited remarkably enhanced OXPHS inhibition and apoptosis inducing ability.
In order to enhance the mitochondria-targeting ability of spinosad. A series of quartenary ammonium spinosyn derivatives was designed and synthesized. Some of the derivatives displayed greatly enhanced antiproliferative ability towards tested human cancer cell lines. The structure activity relationship study indicated that lipophilicity has a great influence on the antiproliferative effects of these derivatives. The most active compound 11d exhibited remarkably enhanced OXPHS inhibition and apoptosis inducing ability than spinosyn A.
In order to improve the antiproliferative activity of naringenin, a naturally occurred flavonoid in citrus fruits, a series of naringenin derivatives with a tertiary amino side chain were prepared. ...The antiproliferative activities of these naringenin derivatives were evaluated on four human cancer cell lines, namely, MCF-7, HCT116, Hela, and A549. Compounds
4a
,
9a
, and
10a
exhibited remarkably enhanced growth inhibition activity. Based on the observed results, the structure–activity relationship of these derivatives was discussed.
Aiming at the disadvantages of converting traditional transient stability margin into power system control measures, this paper proposes a new transient stability margin characterization method based ...on critical cutset transient stability available capacity (TATC). Compared with traditional transient stability margin based on fault clearance time or transient energy function, TATC can directly reflects power system transient stability margin form the view of power which is more conducive for power system planning and operation personnel to grasp system transient stability state, at the same time, is also advantageous for prevention measures and emergency control measures to be developed directly according TATC. Simulation results based on IEEE50 machine 145 bus system show that the proposed TATC can effectively characterize power system transient stability margin.
This study aims to investigate the prevalence and types of drug resistance mutations among patients failing first-line antiretroviral therapy (ART).
Plasma samples from 112 patients with human ...immunodeficiency virus-1 (HIV-1) were collected for virus RNA extract and gene amplification. The mutations related to drug resistance were detected and the incidence was statistically analyzed, and the drug resistance rate against common drugs was also evaluated.
103 cases were successfully amplified, and the main drug resistance mutations in the reverse transcriptase (RT) region were M184V (50.49%), K103N (28.16%), Y181C (25.24%), and K65R (27.18%), while no drug main resistance mutation was found in the protease (PR) region. The incidence of drug resistance mutations was significantly different among patients with different ages, routes of infection, duration of treatment, initial ART regimens and viral load. The drug resistance rate to the common drugs was assessed, including Efavirenz (EFV, 71.84%), Nevirapine (NVP, 74.76%), Lamivudine (3TC, 66.02%), Zidovudine (AZT, 4.85%), Stavudine (D4T, 16.51%), and Tenofovir (TDF, 21.36%).
The drug resistance mutations to NRTIs and NNRTIs are complex and highly prevalent, which was the leading cause of first-line ART failure. This study provides significant theoretical support for developing the second-line and third-line therapeutic schemes.
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