Coumarins are fused benzene and pyrone ring systems with a wide spectrum of bioactivities, including antitumor, anti‐inflammation, antiviral, and antibacterial effects. In this paper, the current ...development of coumarin‐based drugs is introduced, and their structure–activity relationship is discussed by reviewing the relevant literature published in the past 20 years. Coumarin molecules can be customized by the target site to prevent systemic side effects by virtue of structural modification. The ortho‐phenolic hydroxyl on the benzene ring has remarkable antioxidant and antitumor activities. Coumarins with aryl groups at the C‐4 position have good activities in anti‐HIV, antitumor, anti‐inflammation, and analgesia. C‐3 phenylcoumarins have strong anti‐HIV and antioxidant effects. Tetracycline pyranocoumarins can significantly inhibit HIV; osthol structural analogues have antimicrobial activity. Praeruptorin C and its derivatives play an important role in lowering blood pressure and dilating coronary arteries, and khellactone derivatives have significant inhibitory effects on AIDS, cancer, and cardiovascular diseases. It is concluded that the specific site on the core structure of coumarin exhibits one or more activities due to the electronic or steric effects of the substituents. This review is intended to be conducive to rational design and development of more active and less toxic agents with a coumarin scaffold.
Coumarins are naturally occurring, versatile, synthetic compounds with potential anti‐HIV, anticancer, antioxidant, antimicrobial, anti‐inflammatory, analgesic, and anti‐cardiovascular disease activities. This review compiles information from publications on coumarin and its derivatives and proposes structure–activity relationships and structural modification to pave the way for further rational applications of coumarins and the development of related new drugs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Mangroves are widely distributed in the upper part of tropical and subtropical intertidal zones, with the characteristics of high productivity and fast deposition rate. Under the combined action of ...its own growth and microorganisms, mangroves capture, transform and store CO2 in the atmosphere into coastal sediment for a long time, and export some organic carbon from the coastal zone to the offshore and ocean, which is of great significance to prevent coastal erosion and organic carbon burial. In recent years, with the worldwide problems caused by global warming, the concept of carbon neutrality has been widely proposed. Mangroves have attracted extensive attention due to their role in regulating the global carbon cycle. This viewpoint discusses the importance of mangroves to human beings, their role in carbon sequestration and nutrient cycling, their ability to capture CO2, and their carbon sequestration functions and mechanisms, aiming to provide reference for the protection and rational utilization of mangrove resources.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis It was approved by the FDA for the treatment of advanced renal ...cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma （HCC） in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems. Recent studies to the primary resistance, mechanisms are underying the acquired resistance to sorafenib, such as crosstalk involving PI3K/Akt and JAK-STAT pathways, the activation of hypoxia-inducible pathways, and epithelial-mesenchymal transition. Here, we briefly describe the function of sorafenib, its clinical application, and the molecular mechanisms for drug resistance, especially for HCC patients.
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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
bstract
We consider the sensitivity of the DUNE experiment to a heavy neutral lepton, HNL (also known as sterile neutrino) in the mass range from a few MeV to a few GeV, interacting with the ...Standard Model via a transition magnetic moment to the active neutrinos, the so-called dipole portal. The HNL is produced via the up-scattering of active neutrinos, and the subsequent decay inside the detector provides a single-photon signal. We show that the tau-neutrino dipole portal can be efficiently probed at the DUNE far detector, using the tau-neutrino flux generated by neutrino oscillations, while the near detector provides better sensitivity to the electron- and muon-neutrino dipole portal. DUNE will be able to explore large regions of currently unconstrained parameter space and has comparable sensitivity to other planned dedicated experiments, such as SHiP. We also comment briefly on the sensitivity to pure HNL mixing with the tau neutrino at the DUNE far detector.
In this work, we have synthesized a thermoresponsive copolymer, alginate-g-poly(N-isopropylacrylamide) (alginate-g-PNIPAAm) by conjugating PNIPAAm to alginate, where PNIPAAm with different molecular ...weights and narrow molecular weight distribution was synthesized by atomic transfer radical polymerization. The copolymer dissolved in water or phosphate-buffered saline buffer solution at room temperature and formed self-assembled micelles with low critical micellization concentrations when the temperature increased to above their critical micellization temperatures. At higher concentration, that is, 7.4 wt % in water, the copolymer formed solutions at 25 °C and turned into thermosensitive hydrogels when temperature increased to the body temperature (37 °C). Herein, we hypothesized that the thermoresponsive hydrogels could produce self-assembled micelles with the dissolution of the alginate-g-PNIPAAm hydrogels in a biological fluid or drug release medium. If the drug was hydrophobic, the hydrogel eventually could release and produce drug-encapsulated micelles. In our experiments, we loaded the anticancer drug doxorubicin (DOX) into the alginate-g-PNIPAAm hydrogels and demonstrated that the hydrogels released DOX-encapsulated micelles in a sustained manner. The slowly released DOX-loaded micelles enhanced the cellular uptake of DOX in multidrug resistant AT3B-1 cells, showing the effect of overcoming the drug resistance and achieving better efficiency for killing the cancer cells. Therefore, the injectable thermoresponsive hydrogels formed by alginate-g-PNIPAAm and loaded with DOX turned into a smart drug delivery system, releasing DOX-encapsulated micelles in a sustained manner, showing great potential for overcoming the drug resistance in cancer therapy.
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IJS, KILJ, NUK, PNG, UL, UM
Efficient conversion of carbon dioxide (CO
) into value-added products is essential for clean energy research. Design of stable, selective, and powerful electrocatalysts for CO
reduction reaction (CO
...RR) is highly desirable yet largely unmet. In this work, a series of metalloporphyrin-tetrathiafulvalene based covalent organic frameworks (M-TTCOFs) are designed. Tetrathiafulvalene, serving as electron donator or carrier, can construct an oriented electron transmission pathway with metalloporphyrin. Thus-obtained M-TTCOFs can serve as electrocatalysts with high FE
(91.3%, -0.7 V) and possess high cycling stability (>40 h). In addition, after exfoliation, the FE
value of Co-TTCOF nanosheets (~5 nm) is higher than 90% in a wide potential range from -0.6 to -0.9 V and the maximum FE
can reach up to almost 100% (99.7%, -0.8 V). The electrocatalytic CO
RR mechanisms are discussed and revealed by density functional theory calculations. This work paves a new way in exploring porous crystalline materials in electrocatalytic CO
RR.
The abundances of trace elements including Sr, Ga and rare earth elements (REE) and halogens in apatite crystals from four intermediate-felsic plutons in the Zhongdian terrane in the Sanjiang region ...have been determined using electron microprobe and laser ablation inductively coupled plasma mass spectrometry to evaluate the potential of apatite as a petrogenic-metallogenic indicator. The selected plutons include one that is not mineralized (the Triassic Xiuwacu pluton, or the TXWC pluton), one that hosts a porphyry-type Cu deposit (the Pulang pluton, or the PL pluton), one that hosts a porphyry-type Mo deposit (the Tongchanggou pluton, or the TCG pluton), and one that hosts a vein-type Mo deposit (the Cretaceous Xiuwacu pluton, or the CXWC pluton). Except for the CXWC pluton, the other three plutons have adakite-like trace element signatures in whole rocks. The results from this study show that REE, Sr and halogens in apatite can be used to track magma compositions, oxidation states and crystallization history. Apatite crystals from the adakite-like plutons are characterized by much higher Sr/Y and δEu than the non-adakite-type pluton. This means that apatite, which is not susceptible to alteration, is a useful tool for identifying the adakite-like plutons that no longer preserve the initial Sr/Y ratios in whole rocks due to weathering and hydrothermal alteration. Based on apatite Ga contents and δEu values, it is inferred that the parental magmas for the two adakite-like plutons containing porphyry-type Cu and Mo mineralization are more oxidized than that for the non-adakite-type pluton containing vein-type Mo mineralization. Apatite crystals from the vein-type Mo deposit have much lower Cl/F ratios than those from the porphyry-type Cu and Mo deposits. Apatite crystals from the adakite-like pluton without Cu or Mo mineralization is characterized by much lower Cl/F ratios than those from the adakite-like plutons that host the porphyry-type Cu and Mo deposits. The results from this study confirm the apatite is a useful petrogenetic indicator as well as mineral exploration tool.
•Sr, REE and halogens in apatite can track magmas compositions and crystallization history.•The positive correlation of Ga contents with Eu negative anomalies in apatite can indicate oxidation states of magmas.•The combination of Sr/Y ratios and δEu in apatite can identify adakite-like plutons.•Apatite compositions can reveal different magmatic conditions associated with porphyry-type Cu and Mo mineralization, vein-type Mo mineralization and barren mineralization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor ...microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pH
= 6.5, pH
= 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.
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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
In recent years, asymmetric catalysis of ynamides has attracted much attention, but these reactions mostly constructed central chirality, except for a few examples on the synthesis of axially chiral ...compounds which exclusively relied on noble‐metal catalysis. Herein, a facile access to axially chiral N‐heterocycles enabled by chiral Brønsted acid‐catalyzed 5‐endo‐dig cyclization of ynamides is disclosed, which represents the first metal‐free protocol for the construction of axially chiral compounds from ynamides. This method allows the practical and atom‐economical synthesis of valuable N‐arylindoles in excellent yields with generally excellent enantioselectivities. Moreover, organocatalysts and ligands based on such axially chiral N‐arylindole skeletons are demonstrated to be applicable to asymmetric catalysis.
A chiral Brønsted acid‐catalyzed atroposelective cyclization of ynamides is disclosed, which represents the first metal‐free protocol for the construction of axially chiral compounds from ynamides. This method enables the practical and atom‐economical synthesis of valuable N‐arylindoles in excellent yields with generally excellent enantioselectivities.
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