Drug resistance presents serious difficulties for cancer treatment. A combination of paclitaxel (PTX) and lapatinib (LAPA) shows potentials in multiple drug resistant cancers in the clinic, but it is ...almost impossible to deliver these two drugs to the tumor at the same time with the best proportion by simple co-administration of the respective current formualtions for their different pharmacokinetic profiles. Here composite nanocrystals of PTX and LAPA (cNC) were designed with a ratio of 2:1 (
/
), which was their intracellular ratio at the best synergistic efficacy on a drug-resistant cancer cell line (MCF-7/ADR). Such cNC were prepared using a bottom-up method to achieve a nearly spherical appearance and a narrow size distribution of 95.1 ± 2.1 nm. For nanocrystal stabilization, Polyethylene glycol (PEG) coating was introduced into the cNC via polydopamine (PDA) coating in order to get a PEGylated composite nanocrystal (cNC@PDA-PEG) with nanoscale size (170.5 ± 1.4 nm), considerable drug loading (PTX: 21.33 ± 1.48%, LAPA: 10.95 ± 1.24%) and good stability for at least 4 days in plasma-containing buffers. Differential scanning calorimeter (DSC) and XRD data both indicated the different crystalline states of the cNC as well as the cNC@PDA-PEG in comparison with bulk drugs. In vitro release data showed that PTX and LAPA were gradually and completely released from cNC@PDA-PEG in 3 days, while drug release from bulk drugs or cNC was only 30%. cNC@PDA-PEG also showed negligible hemolysis in vitro. Cellular uptake experiments in the MCF-7/ADR cell line showed that the nanocrystals entered the cells in a complete form through endocytosis and then released the drug in the cell. cNC@PDA-PEG inhibits the growth of this drug-resistant cell more effectively than the unmodified version (cNC). In summary, PEGylated PTX and LAPA composite nanocrystals showed the potential for treament of drug-resistant tumors by simultaneously delivering two drugs to tumor cells with the best proportion.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A new series of mollugin-1,2,3-triazole derivatives were synthesized using a copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of corresponding
-propargylated mollugin with aryl azides. ...All the compounds were evaluated for their cytotoxicity on five human cancer cell lines (HL-60, A549, SMMC-7721, SW480, and MCF-7) using MTS assays. Among the synthesized series, most of them showed cytotoxicity and most of all, compounds
and
exhibited significant cytotoxicity of all five cancer cell lines.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The present study aimed to identify the composition of the aerial parts of
L. A chemical investigation on the EtOAc extracts from the aerial parts of
resulted in the isolation of four new ...anthraquinones, namely Cordifoquinone A-D (
-
), along with 16 known anthraquinones. Their structures were elucidated on the basis of NMR and HR-ESIMS data. All isolates were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds
,
and
exhibited significant inhibitory activities with IC
values of 14.05, 23.48 and 29.23 μmol·L
, respectively. Their antibacterial activities of four bacteria,
(ATCC 25922),
subsp.
(ATCC 29213),
subsp.
(ATCC 14028) and
(ATCC 27853), were also evaluated. Our results indicated that the antibacterial activity of these compounds is inactive.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Veronica undulata is a perennial herb, and the complete chloroplast genome (plastome) of V. undulata was determined in this study. The results showed that the plastome size of V. undulata was 151,178 ...bp, including a large single-copy region (68,533 bp), a small single-copy region (21,403 bp), and two inverted repeat regions (25,566 bp). The total GC content of the plastome was 38.1%. We annotated 115 unique genes in the plastome, including 81 protein-coding genes (PCGs), 30 tRNAs, and four rRNAs. Phylogenetic analysis showed that the species of V. undulata and Veronica clustered together.
Research on dual-fuel (DF) engines has become increasingly important as engine manufacturers seek to reduce carbon dioxide emissions. There are significant advantages of using diesel pilot-ignited ...natural gas engines as DF engines. However, different combustion modes exist due to variations in the formation of the mixture. This research used a simulation model and numerical simulations to explore the combustion characteristics of high-pressure direct injection (HPDI), partially premixed compression ignition (PPCI), and double pilot injection premixed compression ignition (DPPCI) combustion modes under a low-medium load. The results revealed that the DPPCI combustion mode provides higher gross indicated thermal efficiency and more acceptable total hydrocarbon (THC) emission levels than the other modes. Due to its relatively good performance, an experimental study was conducted on the DPPCI mode engine to evaluate the impact of the diesel dual-injection strategy on the combustion process. In the DPPCI mode, a delay in the second pilot ignition injection time increased THC emissions (a maximum value of 4.27g/(kW·h)), decreased the emission of nitrogen oxides (a maximum value of 7.64 g/(kW·h)), increased and then subsequently decreased the gross indicated thermal efficiency values, which reached 50.4% under low-medium loads.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A new naphthoquinone derivative (1) together with twenty-three known compounds (2-24), were isolated from the aerial parts of Rubia cordifolia L. Their structures were elucidated on the basis of NMR ...and HR-ESIMS data. Compounds 1-13 were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 2-6 exhibited significant inhibitory activities with IC
50
values of 21.37, 13.81, 24.56, 20.32, and 30.08 μmol·L
−1
, respectively.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Three new compounds (1-3), including novel tetra-
-cresol substituted cyclopenta
naphthalene derivatives, named gastrodinol (1), 2-(4'-hydroxybenzoyl)-3-hydroxyethyl indole (2), ...2-(4'-hydroxybenzoyl)-3-(4''-hydroxybenzyl)indole (3) were isolated from the flower branch of
, along with five known compounds (4-8). Among them, compound 1 exhibited the most anti-microbial activity against
, with the minimum inhibitory concentration of 1 μg ml
. This study demonstrated that the novel gastrodinol 1 found in the flower branch of
may be responsible for the anti-microbial effect. It will lead to the development of new antibiotics, and how to utilize the TCM ''Tianma'' better.
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IJS, KILJ, NUK, UL, UM, UPUK
Pegmatite-type Li deposit is a critical metal, which has been attracting extensive attention. However, its petrogenesis and Li-mineralization mechanism remain under debate. Recently, four types of ...Late Triassic (222−212 Ma) pegmatites are recognized in the Chakabeishan area of Markam–Yajiang–Karakoram (MYK) giant Li ore belt in northern Tibet: tourmaline-, garnet-. spodumene-, and lepidolite-bearing pegmatites. The tourmaline-bearing pegmatites show uniform Nd isotopic compositions (εNd(t) = −13.8 to −14.5), closed to those of the metasedimentary wall rocks (εNd(t) = −15.2 to −17.8), but significantly lower than those of the surrounding Middle Triassic (∼ 244 Ma) syenogranites (εNd(t) = −4.7 to −5.5) that are typical I-type granites. These data, together with their higher Sm/Nd ratios, lower Y and LREE contents relative to the metasedimentary wall rocks, and lack of biotite, demonstrate that the tourmaline-bearing pegmatites were formed by the disequilibrium melting of the metasedimentary wall rocks involving water-absent muscovite dehydration melting with monazite in the residue. From the tourmaline-bearing pegmatites through the garnet-bearing pegmatites to the spodumene- and lepidolite-bearing pegmatites, gradually increasing whole-rock LiBe contents as well as decreasing K/Rb ratios and increasing Cs contents in the K-feldspar and muscovite suggest that they were generated by continuous evolution of magmas similar to the tourmaline-bearing pegmatites. In addition, mineralogical observation and variable Nb and Ta contents in muscovite indicate that the Chakabeishan pegmatites experienced a three-stage evolution process, i.e., magmatic stage for tourmaline- and garnet-bearing pegmatites, coexisting aqueous and silicic magma to hydrothermal transition stage for spodumene-bearing pegmatites, and hydrothermal stage for lepidolite-bearing pegmatites. Taking into account regional geological constraints and our data, we suggest that the low-degree partial melting of clay-rich sedimentary rocks initially control the Li enrichment. The subsequent exsolution and accumulation of a fluid phase during magmatic evolution process occurred in the Li-poor and Li-rich pegmatites, respectively, which is responsible for the further Li mineralization.
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•The barren pegmatites were formed by the muscovite dehydration melting of wall rocks.•The mineralization pegmatites were formed by the extreme differentiation.•Low-degree partial melting of Li-rich source fundamentally control Li mineralization.•A fluid phase dominated by H2O plays a role in Li mineralization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The ability to identify patients with aggressive papillary thyroid microcarcinoma (PTMC) from the low-risk patients is critical to planning proper management of PTMC. Lymph node metastases showed ...association with recurrence and low survival rate, especially in patients with >5 or ≥2 mm metastatic lymph nodes. Therefore, this study aimed to investigate the preoperatively predictive factors of non-small-volume (metastatic lymph nodes >5 or ≥2 mm in size) central lymph node metastases (NSVCLNM) in PTMC patients. A total of 420 patients with clinically node-negative (cN0) PTMC without extrathyroidal extension underwent thyroidectomy plus central neck dissection (CND) between January 2013 and December 2015, were retrospectively analyzed. Of the 420 patients, 33 (7.9%) had NSVCLNM. The 5-year recurrence-free survival was significantly less in cN0 PTMC patients with NSVCLNM, when compared with patients without NSVCLNM (80.8% vs 100%, P < .001). Multivariate logistic regression revealed age ≤36 years (P < .001), male sex (P = .002), ultrasonic tumor sizes of >0.65 cm (P < .001), and ultrasonic multifocality (P = .039) were independent predictive factors of NSVCLNM. A prediction equation (Y = 1.714 × age + 1.361 × sex + 1.639 × tumor size + 0.842 × multifocality -5.196) was developed, with a sensitivity (69.7%) and a specificity (84.0%), respectively, at an optimal cutoff point of -2.418. In conclusion, if the predictive value was >-2.418 according to the equation, immediate surgery including CND rather than active surveillance might be considered for cN0 PTMC patients.
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