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1.
Eur J Pharmacol ; : 174558, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34634308

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, develops rapidly and has a high mortality rate. Relapsed metastasis is the most important factor affecting prognosis and is also the main cause of death for patients with HCC. Cantharidin is a kind of folk medicine for malignant tumors in China. Because of its cytotoxicity, the application of cantharidin is very limited. Magnesium demethylcantharidate (MDC) is a derivative of cantharidin independently developed by our laboratory. Our results show that MDC has anticancer activity and exhibited lower toxicity than cantharidin. However, whether MDC affects the invasion and metastasis of HCC cells and the underlying molecular mechanisms remain obscure. Transwell and Matrigel assays showed that MDC could effectively inhibit the invasion and metastasis of the HCC cell lines SMMC-7721 and SK-Hep1 in a dose-dependent manner. Moreover, MDC significantly inhibited the expression of invasion and metastasis related proteins MMP-2 and MMP-9. In addition, our study found that MDC inhibited the invasion and metastasis of HCC cell lines SMMC-7721 and SK-Hep1 by activating transcription factor FOXO1. Interestingly, the combination of MDC and sorafenib significantly inhibited the invasion and metastasis of HCC cell lines SMMC-7721 and SK-Hep1 compared with the single drug treatment via the activated transcription factor FOXO1. Our work revealed that MDC obviously inhibited the invasion and metastasis of HCC cells, and suggested that MDC could be a potential candidate molecule against the invasion and metastasis of HCC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34614275

RESUMO

We report herein the synthesis, characterization, and coordination chemistry of a free N-aluminylene, namely a carbazolylaluminylene 2b. This species is prepared via a reduction reaction of the corresponding carbazolyl aluminium diiodide. The coordination behavior of 2b towards transition metal centers (W, Cr) is shown to afford a series of novel aluminylene complexes 3-6 with diverse coordination modes. We demonstrate that the Al center in 2b can behave as: 1. a σ-donating and doubly π-accepting ligand; 2. a σ-donating, σ-accepting and π-accepting ligand; and 3. a σ-donating and doubly σ-accepting ligand. Additionally, we show ligand exchange at the aluminylene center providing access to the modulation of electronic properties of transition metals without changing the coordinated atoms. Investigations of 2b with IDippCuCl (IDipp = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) show an unprecedented aluminylene-alumanyl transformation leading to a rare terminal Cu-alumanyl complex 8. The electronic structures of such complexes and the mechanism of the aluminylene-alumanyl transformation are investigated through density functional theory (DFT) calculations.

3.
Plant Physiol ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34618075

RESUMO

Warty fruit in cucumber (Cucumis sativus L.) is an important quality trait that greatly affects fruit appearance and market value. The cucumber wart consists of fruit trichomes (spines) and underlying tubercules, in which the existence of spines is prerequisite for tubercule formation. Although several regulators have been reported to mediate spine or tubercule formation, the direct link between spine and tubercule development remains unknown. Here, we found that the basic Helix-Loop-Helix (bHLH) gene HECATE2 (CsHEC2) was highly expressed in cucumber fruit peels including spines and tubercules. Knockout of CsHEC2 by the CRISPR/Cas9 system resulted in reduced wart density and decreased cytokinin (CTK) accumulation in the fruit peel, whereas overexpression of CsHEC2 led to elevated wart density and CTK level. CsHEC2 is directly bound to the promoter of the CTK hydroxylase-like1 gene (CsCHL1) that catalyzes CTK biosynthesis, and activated CsCHL1 expression. Moreover, CsHEC2 physically interacted with GLABROUS3 (CsGL3, a key spine regulator) and Tuberculate fruit (CsTu, a core tubercule formation factor), and such interactions further enhanced CsHEC2-mediated CsCHL1 expression. These data suggested that CsHEC2 promotes wart formation by acting as an important cofactor for CsGL3 and CsTu to directly stimulate CTK biosynthesis in cucumber. Thus, CsHEC2 can serve as a valuable target for molecular breeding of cucumber varieties with different wart density requirements.

4.
Opt Lett ; 46(19): 4714-4717, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598181

RESUMO

The synergistic integration of optofluidic and surface enhanced Raman scattering (SERS) sensing is a new analytical technique that provides a number of unique characteristics for enhancing the sensing performance and simplifying the design of microsystems. Here, we propose a reusable optofluidic SERS sensor by integrating Au nanoisland substrate (AuNIS)-coated fiber into a microfluidic chip. Through both systematic experimental and theoretical analysis, the sensor enables efficient self-cleaning based on its optical-to-heat-hydrodynamic energy conversion property. Besides, the sensor exhibits the instrument detection limit down to 10-13mol/L and enhancement factor of 106 for Rhodamine 6G. Our optofluidic SERS sensor with such a photothermal microfluidic-assisted self-cleaning method has the advantages of portability, simple operation, and high cleaning efficiency, which will provide a new, to the best of our knowledge, concept and approach for cost-effective and reusable sensors.

5.
Small ; : e2104341, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34622570

RESUMO

Currently, nucleic acid aptamers are exploited as robust targeting ligands in the biomedical field, due to their specific molecular recognition, little immunogenicity, low cost, ect. Thanks to the facile chemical modification and high hydrophilicity, aptamers can be site-specifically linked with hydrophobic moieties to prepare aptamer-organic amphiphiles (AOAs), which spontaneously assemble into aptamer-organic amphiphile self-assemblies (AOASs). These polyvalent self-assemblies feature with enhanced target-binding ability, increased resistance to nuclease, and efficient cargo-loading, making them powerful platforms for bioapplications, including targeted drug delivery, cell-based cancer therapy, biosensing, and bioimaging. Besides, the morphology of AOASs can be elaborately manipulated for smarter biomedical functions, by regulating the hydrophilicity/hydrophobicity ratio of AOAs. Benefiting from the boom in DNA synthesis technology and nanotechnology, various types of AOASs, including aptamer-polymer amphiphile self-assemblies, aptamer-lipid amphiphile self-assemblies, aptamer-cell self-assemblies, ect, have been constructed with great biomedical potential. Particularly, stimuli-responsive AOASs with transformable structure can realize site-specific drug release, enhanced tumor penetration, and specific target molecule detection. Herein, the general synthesis methods of oligonucleotide-organic amphiphiles are firstly summarized. Then recent progress in different types of AOASs for bioapplications and strategies for morphology control are systematically reviewed. The present challenges and future perspectives of this field are also discussed.

6.
Crit Rev Biochem Mol Biol ; : 1-32, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517731

RESUMO

Heme is an essential biomolecule and cofactor involved in a myriad of biological processes. In this review, we focus on how heme binding to heme regulatory motifs (HRMs), catalytic sites, and gas signaling molecules as well as how changes in the heme redox state regulate protein structure, function, and degradation. We also relate these heme-dependent changes to the affected metabolic processes. We center our discussion on two HRM-containing proteins: human heme oxygenase-2, a protein that binds and degrades heme (releasing Fe2+ and CO) in its catalytic core and binds Fe3+-heme at HRMs located within an unstructured region of the enzyme, and the transcriptional regulator Rev-erbß, a protein that binds Fe3+-heme at an HRM and is involved in CO sensing. We will discuss these and other proteins as they relate to cellular heme composition, homeostasis, and trafficking. In addition, we will discuss the HRM-containing family of proteins and how the stability and activity of these proteins are regulated in a dependent manner through the HRMs. Then, after reviewing CO-mediated protein regulation of heme proteins, we turn our attention to the involvement of heme, HRMs, and CO in circadian rhythms. In sum, we stress the importance of understanding the various roles of heme and the distribution of the different heme pools as they relate to the heme redox state, CO, and heme binding affinities.

7.
Mol Med Rep ; 24(5)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34476508

RESUMO

Pathological scars mainly refer to hypertrophic scars and keloids, and have a high incidence. Moreover, these scars seriously affect the patient's appearance and are associated with significant pain. The present study aimed to investigate the inhibitory effect of microRNA (miR)­29a from human adipose­derived mesenchymal stem cells (hADSCs) exosomes on scar formation. Firstly, the expression of miR­29a in thermal skin tissues of mice and human hypertrophic scar fibroblasts (HSFBs) was detected via reverse transcription­quantitative PCR. Exosomes derived from miR­29a­modified hADSCs were extracted and the influence of miR­29a­modified hADSCs­exo on the proliferation and function of HSFBs was determined. Lastly, the effect of miR­29a­modified hADSCs­exo on scar formation was determined using a thermal mouse model. The results demonstrated that miR­29a was downregulated in scar tissues after scalding and in HSFBs. After treating HSFBs with miR­29a­modified hADSC exosomes, miR­29a­overexpressing hADSC exosomes inhibited the proliferation and migration of HSFBs. Moreover, it was found that TGF­ß2 was the target of miR­29a, and that hADSC exosome­derived miR­29a inhibited the fibrosis of HSFBs and scar hyperplasia after scalding in mice by targeting the TGF­ß2/Smad3 signaling pathway. In summary, the current data indicated that miR­29a­modified hADSC exosome therapy can decrease scar formation by inhibiting the TGF­ß2/Smad3 signaling pathway via its derived exogenous miR­29a, and this may be useful for the future treatment of pathological scars by providing a potential molecular basis.

8.
J Am Chem Soc ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533932

RESUMO

As a fundamental chemical property, aromaticity guides the synthesis of novel structures and materials. Replacing the carbon moieties of aromatic hydrocarbons with transition metal fragments is a promising strategy to synthesize intriguing organometallic counterparts with a similar aromaticity to their organic parents. However, since antiaromaticity will endow compound instability, it is a great challenge to obtain an antiaromatic organometallic counterpart based on such transition metal replacement in aromatic hydrocarbons. Here, we report an efficient aromaticity transformation on aromatic naphthalene through the bridgehead replacement of an osmium fragment, leading to the unprecedented synthesis of metal-bridgehead naphthalene featuring a highly twisted structure as confirmed by X-ray crystallography characterization. Such a twisted conformation works together with its phosphonium substituents to release the antiaromaticity in the planar conformation of the metal-bridgehead naphthalene. Our findings prove the bridgehead involvement of transition metals in unexpected aromaticity modifications and open an avenue for novel metal-bridgehead complexes.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34536251

RESUMO

An unprecedented and general hydroboration of alkenes with BX3(X = Br, Cl) as the boration reagent in the presence of iPr2NEt is reported. The addition of iPr2NEt not only suppresses alkene polymerization and haloboration side reactions but also provides an "H" source for hydroboration. More importantly, the site-fixed installation of a boryl group at the original position of the internal double-bond is readily achieved as compared with conventional transition-metal-catalyzed hydroboration processes. Further application to the synthesis of 1, n-diborylalkanes (n=3-10) is also demonstrated. Preliminary mechanistic studies reveal a major reaction pathway that involves radical species and operates through frustrated-Lewis-pair-type single-electron transfer mechanism.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34559509

RESUMO

Poisons and poisonous weapons in armed conflict, especially chemical warfare agents (CWAs), pose serious threats to global security. Porous materials have recently been regarded as promising candidates to defend personnel in a CWA-contaminated environment, but challenges remain for integrating these materials into protective garments without sacrificing the intrinsic flexibility of fibers. Here, we report a rigid-flexible coupling hypercross-linking methodology to create flexible sponge-like nanofibers featuring hierarchical radial gradient porous nanoarchitectures, in which the inner structure is a mesoporous multichambered network, and the outer structure is a dense domain with a microporous network structure. Experimental and computational evidence supports the contention that sponge nanofibers with distinctive pore topology and robust bendability can be designed by manipulating the flexibility of building blocks. The resulting heterogeneous nanofibers exhibit integrated properties of spatially selective superstructures, abundant micropores, interconnected mesopores, a high surface area (579 m2 g-1), remarkable flexibility, and exceptional CWA affinity, which are extraordinarily effective for adsorptive performance (498 mg g-1). The successful synthesis of these materials might inspire the development of chemical protective materials in an efficient, self-standing, and structurally adaptive form.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34383655

RESUMO

We consider composition problems of the form , which are important for machine learning. Although gradient descent and stochastic gradient descent are straightforward solutions, the essential computation of in each single iteration is expensive, let alone for large m. In this article, we devise a stochastically controlled compositional gradient algorithm. Specifically, we introduce two variants of stochastically controlled technique to estimate the inner function G(x) and the gradient of the objective function, respectively. The computational cost is largely reduced. However, the natural needs of two stochastic subsets D1 and D2 form direct barriers to guarantee the convergence of the algorithm, especially the theoretical proof of the convergence. To this end, we present a general convergence analysis by proving and , through which the proposed method significantly improve composition algorithms under low target accuracy (i.e., 1/ε≪ m or n) in both strongly convex and nonconvex settings. Comprehensive experiments demonstrate the superiority of the proposed method over existing methods.

12.
J Am Chem Soc ; 143(34): 13483-13488, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34427439

RESUMO

BN/CC isosterism can give rise to attractive molecules with unique physical or chemical properties. We report here the synthesis, characterization, and reactivities of the boraiminolithium species 2, a room-temperature-stable crystalline solid accessible through a facile dehydrohalogenation/deprotonation reaction. This species, bearing a polarized B≡N triple bond and an anionic N center, is the first example of a BN analogue to the well-known alkynyllithium molecules (lithium acetylides). It has demonstrated a remarkable ability for iminoborane-transfer reactions, which allows for the isolation of a series of unprecedented N-functionalized iminoboranes as well as novel main-group heterocycles. Stable boraiminolithium reagents may become powerful tools in the exploration of new BN-containing building blocks for synthetic chemistry and materials science.

13.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360535

RESUMO

The aims of this study were to develop the magnolol-chitosan films and study the positive effect of the combination of magnolol and chitosan. The addition of magnolol made the magnolol-chitosan films exhibit higher density (1.06-1.87 g/cm3), but the relatively lower water vapor permeability (12.06-7.36 × 10-11·g·m-1·s-1·Pa-1) and water content (16.10-10.64%). The dense and smooth surface and cross-section of magnolol-chitosan films were observed by environmental scanning electron microscopy (ESEM) images. The interaction of magnolol and chitosan was observed by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). After the addition of magnolol, the antioxidant capacity of magnolol-chitosan films was increased from 18.99 to 82.00%, the growth of P. aeruginosa was inhibited and the inhibition percentage of biofilm formation was increased from 30.89 to 86.04%. We further verified that the application of magnolol-chitosan films on chilled pork significantly reduced the increases in pH value, inhibited the growth of microorganisms and extended the shelf life. Results suggest that magnolol had a positive effect on magnolol-chitosan films and could be effectively applied to pork preservation.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/farmacologia , Quitosana/química , Conservação de Alimentos/métodos , Lignanas/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Embalagem de Alimentos/métodos , Carne de Porco/análise , Infecções por Pseudomonas/microbiologia , Suínos
14.
Int J Drug Policy ; 97: 103408, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34411957

RESUMO

This study offers rare empirical data and insight about the experiences of women who use and sell drugs in China and their participation in the drug economy. Drug selling is traditionally viewed as a male job in China and commonly overlaps with drug use practices. While this largely male-dominated economy has been widely documented, very little is known about the experiences of women. Drawing on interviews with twelve women, this exploratory study aims to shed light on the lives and experiences of women who use and sell drugs in China. Findings indicate that for study participants, entering into the drug selling economy was primarily driven by motives of maintaining their own drug use. Our analysis also shows that participants kept their drug selling within limited social circles. Instead of seeking to make large profits, they often aimed to "help friends" and secure drugs for their own use. Women who sold drugs in our study usually affiliated themselves with their male partners, often purposefully utilizing feminine characteristics and practices to serve gendered roles in drug selling. In doing so, this paper brings to light the gendered nature of drug selling practices and drug market relations in China and more broadly.

15.
J Ethnopharmacol ; 280: 114485, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34348195

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Taodan granules (TDG) have been observed to decrease interleukins, or psoriasis area and severity index (PASI) score for psoriasis vulgaris, without significant adverse events. However, the regulatory network remains elucidated. AIM OF THE STUDY: The objective is to identify critical genes and kernel pathways of TDG treated psoriasis. MATERIALS AND METHODS: Firstly, construct a network of components-targets of TDG using network pharmacology. Secondly, the ClusterONE algorithm was used to build a modular network and identify critical genes and corresponding pathways. Thirdly, the critical genes and kernel pathways were verified in imiquimod (IMQ) induced psoriasis-like mice model. RESULTS: The results validated that TDG downregulated the mRNA expression of MMP2 (degree = 5, P < 0.05), IL6 (degree = 9, P < 0.05), TNF (degree = 14, P < 0.05), CCL2 (degree = 8, P < 0.05), CXCL2 (degree = 8, P < 0.05), IL1B (degree = 9, P < 0.05), and JUN (degree = 9, P < 0.05), while upregulated IL10 (degree = 8) expression. Besides, TDG were observed to regulate IL17 signaling pathway and TNF signaling pathway (size = 18), via the skin tissue homogenate of psoriasis-like mice. CONCLUSION: In summary, this study identified the potential targets and pathways, providing additional evidence for the clinical application of TDG treated psoriasis.

16.
Anal Chem ; 93(36): 12447-12455, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34449219

RESUMO

Alzheimer's disease (AD), known as a progressive neurodegenerative disorder, has had a terrible impact on the health of aged people. Due to its severity, early diagnosis of AD is significant to retard the progress and provide timely treatment. Here, we report a fluorescence ratio detection of AD biomarker amyloid ß oligomers (AßOs) by combining highly doped upconversion nanoparticles-SiO2@metal-organic framework/black hole quencher (H-USM/BHQ-1) microspheres with optical tweezer (OT) microscopic imaging. Optical trapping a single microsphere not only avoids the interference of fluid viscosity but also provides a high power density laser source to efficiently stimulate upconversion luminescence (UCL) of highly doped upconversion nanoparticles (H-UCNPs). Under this condition, H-UCNPs show stronger UCL and greater power-dependent properties compared to low-doped ones. Moreover, the closely packed quenching molecules BHQ-1 on a metal-organic framework (ZIF-8) exhibit excellent quenching efficiency for upconversion 525 and 540 nm emission. Also, the luminescent resonance energy transfer efficiency reaches 89.58%. When different concentrations of AßOs are present, the UCL540 recovers due to the decomposition of ZIF-8 and the release of BHQ-1. Using 540 and 654 nm emission ratio of highly doped UCNPs as reporters, the limit of detection reaches 28.4 pM for the quantitative determination of AßOs. Besides, this strategy is able to selectively quantify the AßO concentration. Therefore, we demonstrated the combination of optical trapping and highly doped UCNPs which is applied for the detection of AßOs with high sensitivity and specificity.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Idoso , Peptídeos beta-Amiloides , Humanos , Microesferas , Dióxido de Silício
17.
Br J Pharmacol ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34460100

RESUMO

BACKGROUND AND PURPOSE: Psoriasis is a chronic inflammatory skin disease associated with both innate and adaptive immune responses. The stimulator of interferon genes (STING) protein engages in sensing of cytosolic DNA to initiate dsDNA-driven immune response. In vitro and in vivo anti-psoriasis effects of STING antagonist H-151 were explored. EXPERIMENTAL APPROACH: We analyzed the gene expression profile of STING and related downstream targets in the skin samples of healthy people and psoriasis patients from GEO database. Cellular inhibitory activity of H-151 on STING pathway was confirmed via qPCR and western blotting. The preventive effect of topical application of H-151 on imiquimod (IMQ)-induced psoriatic mice was examined through histological, immunohistochemical, immunofluorescent, flow cytometric analysis, ELISA Kits and other approaches. Preliminary mechanistic studies were also performed. KEY RESULTS: Gene expressions of STING and its downstream target were upregulated in lesional skins of psoriasis patients. Topical administration of H-151 attenuated the skin lesions in IMQ-induced psoriatic mouse model, while the secretion of proinflammatory cytokines (IL-17, IL-23 and IL-6), M1 macrophage infiltration and Th17 cells differentiation were significantly suppressed by H-151 treatment. Mechanistically, H-151 inhibited STING/NF-κB signaling in both keratinocytes and immune cells. CONCLUSION AND IMPLICATIONS: H-151 displayed anti-inflammatory activity in both keratinocytes and immune cells, and decreased the severity of psoriatic response in vivo. Inhibition of STING signaling pathway may represent a novel therapeutic approach to psoriasis and related complications.

18.
Int J Biol Macromol ; 189: 346-355, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34428489

RESUMO

Finasteride is an antiandrogenic drug used for the clinical treatment of chronic nonbacterial prostatitis (CNP). Recently, we reported the anti-CNP activity of Poria cocos polysaccharides (PPs) in a rat model. In this study, we compared the differences between PPs and finasteride in treating CNP, especially their effects on the gut microbiota. Results showed that both PPs and finasteride significantly reduced the prostate weight and prostate index of CNP rats, and improved the histological damages in the inflamed prostate. Moreover, PPs and finasteride inhibited the production of pro-inflammatory cytokines (TNF-α, IL-2 and IL-8) and androgens (dihydrotestosterone and testosterone). By 16S rDNA sequencing, PPs and finasteride were found to reprogram the gut microbiota into distinct profiles. Further analysis presented that PPs but not finasteride recovered CNP-induced changes in the gut microbiota, including Ruminococcaceae NK4A214 group, uncultured bacterium f Ruminococcaceae, Ruminiclostridium 9, Phascolarctobacterium, Coriobacteriaceae UCG-002 and Oribacterium. LDA effect size (LEfSe) analysis revealed that PPs recovered the gut microbiota by targeting Ruminococcaceae NK4A214 group. Our results suggested that PPs alleviated CNP via different mechanisms from finasteride, especially by regulating the gut microbiota, which offers therapeutic target for the treatment of CNP.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34370673

RESUMO

Imitation learning from observation (LfO) is more preferable than imitation learning from demonstration (LfD) because of the nonnecessity of expert actions when reconstructing the expert policy from the expert data. However, previous studies imply that the performance of LfO is inferior to LfD by a tremendous gap, which makes it challenging to employ LfO in practice. By contrast, this article proves that LfO is almost equivalent to LfD in the deterministic robot environment, and more generally even in the robot environment with bounded randomness. In the deterministic robot environment, from the perspective of the control theory, we show that the inverse dynamics disagreement between LfO and LfD approaches zero, meaning that LfO is almost equivalent to LfD. To further relax the deterministic constraint and better adapt to the practical environment, we consider bounded randomness in the robot environment and prove that the optimizing targets for both LfD and LfO remain almost the same in the more generalized setting. Extensive experiments for multiple robot tasks are conducted to demonstrate that LfO achieves comparable performance to LfD empirically. In fact, the most common robot systems in reality are the robot environment with bounded randomness (i.e., the environment this article considered). Hence, our findings greatly extend the potential of LfO and suggest that we can safely apply LfO in practice without sacrificing the performance compared to LfD.

20.
Angew Chem Int Ed Engl ; 60(38): 20833-20839, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34288320

RESUMO

The sequence-dependent DNA secondary structures possess structure polymorphism. To date, studies on regulated ligands mainly focus on individual DNA secondary topologies, while lack focus on quadruplex-duplex hybrids (QDHs). Here, we design an organic-metal hybrid ligand L1 Pt(dien), which matches and selectively binds one type of QDHs with lateral duplex stem-loop (QLDH) with high affinity, while shows poor affinity for other QDHs and individual G4 or duplex DNA. The solution structure of QLDH MYT1L-L1 Pt(dien) complex was determined by NMR. The structure reveals that L1 Pt(dien) presents a chair-type conformation, whose large aromatic "chair surface" intercalates into the G-quadruplex-duplex interface via π-π stacking and "backrest" platinum unit interacts with duplex region through hydrogen bonding and electrostatic interactions, showing a highly matched lock-key binding mode. Our work provided guidance for spatial matching design of selectively targeting ligands to QDH structures.

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