Epithelial-to-mesenchymal transition (EMT) is a transcriptionally governed process by which cancer cells establish a front-rear polarity axis that facilitates motility and invasion. Dynamic assembly ...of focal adhesions and other actin-based cytoskeletal structures on the leading edge of motile cells requires precise spatial and temporal control of protein trafficking. Yet, the way in which EMT-activating transcriptional programs interface with vesicular trafficking networks that effect cell polarity change remains unclear. Here, by utilizing multiple approaches to assess vesicular transport dynamics through endocytic recycling and retrograde trafficking pathways in lung adenocarcinoma cells at distinct positions on the EMT spectrum, we find that the EMT-activating transcription factor ZEB1 accelerates endocytosis and intracellular trafficking of plasma membrane-bound proteins. ZEB1 drives turnover of the MET receptor tyrosine kinase by hastening receptor endocytosis and transport to the lysosomal compartment for degradation. ZEB1 relieves a plus-end-directed microtubule-dependent kinesin motor protein (KIF13A) and a clathrin-associated adaptor protein complex subunit (AP1S2) from microRNA-dependent silencing, thereby accelerating cargo transport through the endocytic recycling and retrograde vesicular pathways, respectively. Depletion of KIF13A or AP1S2 mitigates ZEB1-dependent focal adhesion dynamics, front-rear axis polarization, and cancer cell motility. Thus, ZEB1-dependent transcriptional networks govern vesicular trafficking dynamics to effect cell polarity change.
A series of novel myrtenal derivatives bearing 1,2,4-triazole moiety were designed and synthesized by multi-step reactions in an attempt to develop potent antifungal agents. Their structures were ...confirmed by using UV-vis, FTIR, NMR, and ESI-MS analysis. Antifungal activity of the target compounds was preliminarily evaluated by the in vitro method against
f. sp.
,
,
,
, and
at 50 µg/mL. Compounds
(R =
-Pr),
(R =
-NO₂ Bn), and
(R = Et) exhibited excellent antifungal activity against
with inhibition rates of 98.2%, 96.4%, and 90.7%, respectively, showing better or comparable antifungal activity than that of the commercial fungicide azoxystrobin with a 96.0% inhibition rate, which served as a positive control.
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Twenty-seven (
)- and (
)-verbenone derivatives bearing an oxime ester moiety were designed and synthesized in search of novel bioactive molecules. Their structures were confirmed by UV-Vis, FTIR, ...NMR, ESI-MS, and elemental analysis. The antifungal and herbicidal activities of the target compounds were preliminarily evaluated. As a result, compound (
)-
(R =
-pyridyl) exhibited excellent antifungal activity with growth inhibition percentages of 92.2%, 80.0% and 76.3% against
,
, and
at 50 µg/mL, showing comparable or better antifungal activity than the commercial fungicide chlorothalonil with growth inhibition of 96.1%, 75.0% and 73.3%, respectively, and 1.7-5.5-fold more growth inhibition than its stereoisomer (
)-
(R =
-pyridyl) with inhibition rates of 22.6%, 28.6% and 43.7%, respectively. In addition, seven compounds displayed significant growth inhibition activity of over 90% against the root of rape (
) at 100 µg/mL, exhibiting much better herbicidal activity than the commercial herbicide flumioxazin with a 63.0% growth inhibition. Among these seven compounds, compound (
)-
(R =
-pyridyl) inhibited growth by 92.1%, which was 1.7-fold more than its stereoisomer (
)-
(R =
-pyridyl) which inhibited growth by 54.0%.
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•GO-QACSA was synthesized for remelt syrup decolorization in sugar refinery.•Cytotoxicity tests were performed to evaluate the food safety of GO-QACSA.•GO-QACSA adsorbed HRSADPs well ...and quickly, as well as exhibited good recyclability.•Interaction mechanisms for HRSADP adsorption on GO-QACSA were studied.•New insights into the mass transfer behaviors of the adsorption system were provided.
The decolorization of remelt syrup is the most critical step in the sugar refining process as it directly affects the quality of refined sugar. Adsorption is a useful method that can be applied to decolorize the syrup. A quaternary ammonium-functionalized chitosan/graphene oxide composite aerogel (GO-QACSA) was developed as an effective adsorbent for the removal of high-molecular-weight reducing sugar alkaline degradation products (HRSADPs), the main class of colorants in remelt syrup. The advantages of GO-QACSA to remove HRSADPs can be attributed to its well-connected 3-D network-like porous structure, nontoxicity, high hydrophilicity, and the richness of quaternary ammonium groups. The equilibrium adsorption capacity of GO-QACSA for HRSADPs reached 364.09 mg/g and the removal rate was > 90%. GO-QACSA exhibited an ultra-fast adsorption rate. Recycling experiments indicated that GO-QACSA exhibited good renewability and reusability. The interaction mechanism for the adsorption of HRSADP on GO-QACSA was studied, and the results revealed that two layers of HRSADPs adhered to the surface of GO-QACSA via electrovalent bonds formed between the quaternary ammonium and carboxylate groups. On average, 2–3 carboxylate ions in one HRSADP molecule bonded with the quaternary ammonium cations of GO-QACSA. Four phenomenological mathematical models, namely, External mass transfer resistance (EMTR), Internal mass transfer resistance (IMTR), combined EMTR–IMTR, and Adsorption on active sites (AAS), were presented based on the best-fit equilibrium isotherms. These models could be used to provide new insights into the adsorption mass transfer behaviors of the system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To discover novel potent cytotoxic diterpenoids, a series of hybrids of dehydroabietic acid containing 1,2,3-triazole moiety were designed and synthesized. The target compounds were characterized by ...means of FT-IR,
H NMR,
C NMR, ESI-MS and elemental analysis techniques. The in vitro cytotoxicity of these compounds was evaluated by standard MTT (methyl thiazolytetrazolium) assay against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), BEL-7402 (liver) human carcinoma cell lines and human normal liver cell (HL-7702). The screening results revealed that most of the hybrids showed significantly improved cytotoxicity over parent compound DHAA. Among them, 1-(3-fluorobenzyl)-1
-1,2,3-triazole-4-yldehydroabietic acid methyl ester (
), and 1-(2-nitrobenzyl)-1
-1,2,3-triazole-4-yldehydroabietic acid methyl ester (
) displayed better antiproliferative activity with IC
(50% inhibitory concentration) values of 5.90 ± 0.41 and 6.25 ± 0.37 µM toward HepG2 cells compared to cisplatin, while they exhibited lower cytotoxicity against HL-7702. Therefore, the 1,2,3-triazole-hybrids could be a promising strategy for the synthesis of antitumor diterpenoids and it also proved the essential role of 1,2,3-triazole moiety of DHAA in the biological activity.
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Water contamination caused by discharge of spent washes containing colorants remains controversial. In this study, rosin-derived strongly basic macroporous anion-adsorption resin (RSBMAR) was ...designed as an advanced adsorbent for scavenging caramel, the most recalcitrant colorant in spent washes. Toxicity tests suggest that RSBMAR is environmentally friendly and hardly threatens aquatic organisms. RSBMAR exhibits outstanding caramel capture efficiency because of its rich target quaternary ammonium (−R4N+) and protonated tertiary amine (−R3NH+) groups, abundant porous structure, large specific surface area, excellent thermal stability, and good sphericity. The caramel adsorption capacity of RSBMAR was 165.86 mg/g and the decolorization efficiency reached 96.75%. After five cycles, the spent RSBMAR maintained a high decolorization rate, indicating excellent renewability. Multiple characterizations indicated that caramel capture was largely mediated by charge interaction between −R4N+/−R3NH+ (RSBMAR) and −RCOO−/−RCOOH (caramel), followed by H-bonds. Quantum chemical theory simulations, including electrostatic potential, local ionization energy, frontier molecular orbitals, and independent gradient model analyses, further visualized caramel capture mechanisms at atomic level. Hirshfeld surface analysis revealed that RSBMAR acts as both an H-bond donor and acceptor during caramel uptake. Dynamic adsorption was performed to treat real wastewater, laying the foundation for the industrial application of RSBMAR.
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•RSBMAR is firstly designed as an effective green adsorbent for caramel scavenging.•Caramel uptake of RSBMAR is nine times that of the only reported caramel scavenger.•Multiple QCTSs coupled with experimental analyses decipher adsorption mechanisms.•Hirshfeld surface and independent gradient model analyses reveal H-bond interaction.•Caramel capture mechanisms are visualized from atomic and electronic perspectives.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In the search for novel compounds with both survivin inhibitory activity and fluorescence properties, 18 novel longifolene-derived tetralin pyrimidine compounds were designed using survivin as the ...target and synthesized from the sustainable natural resource longifolene. Their structures were confirmed by IR, NMR, ESIMS, and elemental analysis. The
in vitro
antiproliferative activities of the target compounds were preliminarily evaluated using the standard MTT assay against MGC-803 (human gastric cancer cell), T24 (human bladder cancer cell), HepG2 (human liver cancer cell), and A549 (human lung adenocarcinoma cell). As a result, some of the target compounds showed better antiproliferative activities than the positive control drug 5-FU, in which, compound
5m
had an IC
50
of 1.42 μM against MGC-803 and compound
5l
had an IC
50
of 1.79 μM against T24, exhibiting excellent activity. Additionally, the target compounds display moderate or even low cytotoxicity toward human normal liver cells L02. Subsequently, a reasonable and effective 3D-QSAR model was established to study the relationship between the structure of the target compounds and antiproliferative activities and was employed to construct two new compounds with potentially better activity. Meanwhile, molecular docking was performed to study the interaction mode between the compound
5m
and survivin protein. Furthermore, the target compounds with significant antiproliferative activity showed noticeable fluorescence properties.
In the search for novel compounds with both survivin inhibitory activity and fluorescence properties, 18 novel longifolene-derived tetralin pyrimidine compounds were designed using survivin as the target and synthesized from the sustainable natural resource longifolene.
Pinecone-based biomass carbon (PC) is a potential anode material for potassium-ion batteries because it is abundant, cheap, renewable, and easy to obtain. However, because of inferior kinetics and ...the effects of volume expansion due to the large radius of the K
+
ion, it does not meet commercial performance requirements. In this study, nitrogen-doped PC (NPC) was prepared by carbonization in molten ZnCl
2
with urea as a nitrogen source. A strategy based on synergistic effects between N doping and ZnCl
2
molten salt was used to produce a hierarchically porous pie-like NPC with abundant defects and active sites and an enlarged interlayer distance-properties that enhance K
+
adsorption, promote K
+
intercalation/diffusion, and reduce the effects of volume expansion. This NPC exhibited a high reversible capacity (283 mA h g
−1
at 50 mA g
−1
) and superior rate performance and cyclic stability (110 mA h g
−1
after 1000 cycles at 5 A g
−1
), demonstrating its potential for use in potassium-ion batteries.
Pinecone-based biomass carbon (PC) is a potential anode material for potassium-ion batteries because it is abundant, cheap, renewable, and easy to obtain.
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Novel representatives of the important group of biologically-active, dehydroabietic acid-bearing oxazolidinone moiety were synthesized to explore more efficacious and less toxic antitumor agents. ...Structures of all the newly target molecules were confirmed by IR, ¹H-NMR,
C-NMR, and HR-MS. The inhibitory activities of these compounds against different human cancer cell lines (MGC-803, CNE-2, SK-OV-3, NCI-H460) and human normal liver cell line LO2 were evaluated and compared with the commercial anticancer drug cisplatin, using standard MTT (methyl thiazolytetrazolium) assay in vitro. The pharmacological screening results revealed that most of the hybrids showed significantly improved antiproliferative activities over dehydroabietic acid and that some displayed better inhibitory activities compared to cisplatin. In particular, compound
exhibited promising cytotoxicity with IC
values ranging from 3.82 to 17.76 µM against all the test cell lines and displayed very weak cytotoxicity (IC
> 100 µM) on normal cells, showing good selectivity between normal and malignant cells. Furthermore, the action mechanism of the representative compound
was preliminarily investigated by Annexin-V/PI dual staining, Hoechst 33258 staining, which indicated that the compound can induce cell apoptosis in MGC-803 cells in a dose-dependent manner and arrest the cell cycle in G1 phase. Therefore,
may be further exploited as a novel pharmacophore model for the development of anticancer agents.
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A series of novel acyl thiourea compounds containing
gem
-dimethylcyclopropane ring were designed and synthesized by multi-step reactions in search of novel antifungal molecules. Structures of all ...the target compounds were characterized by spectral techniques of UV–vis, FT-IR,
1
H-NMR,
13
C-NMR, and ESI–MS. The antifungal activity of the target compounds was preliminarily evaluated by agar dilution method. The antifungal bioassay revealed that, at 50 μg/mL, compounds
5h
(R =
o
-F),
5m
(R =
p
-Br), and
5n
(R =
o
-NO
2
) showed the same antifungal activity of 73.6% against
Physalospora piricola
, which was comparable than that of the positive control. Furthermore, against
Gibberella zeae
, compounds
5k
(R =
m
-Cl),
5l
(R =
m
-Br),
5m
(R =
p
-Br), and
5n
(R =
o
-NO
2
) displayed the same antifungal activity of 75.6%, and compound
5o
(R =
p
-NO
2
) displayed antifungal activity of 78.8%, which were all better than that of the positive control. The preliminary analysis of 3D-QSAR model was performed to study the effect of molecular structure on biological activity using the comparative molecular field analysis (CoMFA) method. The results showed 3D-QSAR model (
r
2
= 0.995,
q
2
= 0.503) was reasonable and effective.
Graphic abstract
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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
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