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Intelligent DNA nanomachines are powerful and versatile molecular tools for bioimaging and biodiagnostic applications; however, they are generally constrained by complicated synthetic processes and poor reaction efficiencies. In this study, we developed a simple and efficient molecular machine by coupling a self-powered rolling motor with a lipidic nanoflare (termed RMNF), enabling high-contrast, robust, and rapid probing of cancer-associated microRNA (miRNA) in serum and living cells. The lipidic nanoflare is a cholesterol-based lipidic micelle decorated with hairpin-shaped tracks that can be facilely synthesized by stirring in buffered solution, whereas the 3D rolling motor (3D RM) is a rigidified tetrahedral DNA scaffold equipped with four single-stranded “legs” each silenced by a locking strand. Once exposed to the target miRNA, the 3D RM can be activated, followed by self-powered precession based on catalyzed hairpin assembly (CHA) and lighting up of the lipidic nanoflare. Notably, the multivalent 3D RM that moves using four DNA legs, which allows the motor to continuously and acceleratedly interreact with DNA tracks rather than dissociate from the surface of the nanoflare, yielded a limit of detection (LOD) of 500 fM at 37 °C within 1.5 h. Through the nick-hidden and rigidified structure design, RMNF exhibits high biostability and a low false-positive signal under complex physiological settings. The final application of RMNF for miRNA detection in clinical samples and living cells demonstrates its considerable potential for biomedical imaging and clinical diagnosis.

DNA nanotechnology has shown great promise for biosensing and molecular recognition. However, the practical application of conventional DNA biosensors is constrained by inadequate target stimuli, intricate design schemes, multicomponent systems, and susceptibility to nuclease degradation. To overcome these limitations, we present a class of starlike branched and multiplex embedded system (SBES) with an integrated functional design and cascade exponential amplification for serum microRNA (miRNA) detection. The DNA arms can be integrated into an all-in-one system by surrounding a branch point, with each arm endowed with specific functionalities by embedding different DNA fragments. These fragments include a segment complementary to the target miRNA for the recognition element, palindromic tails for self-primed polymerization, and a region with the same sequences as the target serving as the target analogue. Upon exposure to a target miRNA, the DNA arms unwind in a stepwise manner through palindrome-mediated dimerization and polymerization. This enables target recycling for subsequent reactions while releasing the target analogue to generate a secondary response in a feedback manner. A comparative analysis illustrates that the signal-to-noise ratio (SNR) of a full SBES with a feedback strategy is approximately 250% higher than the system without a feedback design. We demonstrate that the four-arm 4pSBES has the benefits of multifunctional integration, enhanced sensitivity, and low false-positive signals, which makes this approach ideally suited for clinical diagnosis. Moreover, an upgraded SBES with additional DNA arms (e.g., 6pSBES) can be constructed to allow multifunctional extension, offering unprecedented opportunities to build versatile DNA nanostructures for biosensing.

Enzyme-free DNA strand displacement process is often practical when detecting miRNAs expressed at low levels in living cells. However, the poor kinetics, tedious reaction period, and multicomponent system hamper its in vivo applications to a great extent. Herein, we design a branch-shaped trapping device (BTD)-based spatial confinement reactor and applied it for accelerated miRNA in situ imaging. The reactor consists of a pair of trapped probe-based catalyzed hairpin assembly (T-CHA) reactions attached around the BTD. The trapping device naturally offered CHA reactions a good spatial-confinement effect by integrating the metastable probes (MHPa and MHPb) of the traditional CHA with the four-branched arm of BTD, which greatly improved the localized concentration of probes and shortened their physical distance. The autonomous and progressive walk of miRNA on the four-arm nanoprobes via T-CHA can rapidly tie numerous four-arm nanoprobes into figure-of-eight nanoknots (FENs), yielding strong fluorescence that is proportional to the miRNA expression level. The unique nanoarchitecture of the FEN also benefits the restricted freedom of movement (FOM) in a confined cellular environment, which makes the system ideally suitable for in situ imaging of intracellular miRNAs. In vitro and in situ analyses also demonstrated that the T-CHA overall outperformed the dissociative probe-based CHA (D-CHA) in stability, reaction speed, and amplification sensitivity. The final application of the T-CHA-based four-arm nanoprobe for imagings of both cancer cells and normal cells shows the potential of the platform for accurately and timely revealing miRNA in biological systems.

Though hepatotoxicity induced by the ubiquitous and potentially ingested nanoplastics (NPs) has been extensively studied, limited attention has been given to the role of NPs' surface topography. Since these ingested NPs pass through the human digestive system (HDS) before reaching the liver, their surface properties are altered, which affects their interactions with the organ. Herein, we prepared two different-sized aggregation-induced emission fluorogen-incorporated NPs (AIE-NPs) with diverse surface roughness by exposing NPs to the HDS for different durations. The HDS environment could effectively alter the surface roughness of the AIE-NPs, leading to an extended specific surface area and decreased hydrophobicity. Besides, roughening the NPs' surface facilitated their cellular internalization efficiency, mainly mediated by the specific surface area, which has been confirmed in vivoin a zebrafish model. After internalization, all these investigated AIE-NPs were consistently localized in lysosomes (Pearson's correlation coefficient > 0.8), suggesting that the surface roughness had negligible influence on their intracellular distribution pattern. The AIE-NPs with the rougher surface contributed to lysosomal alkalization and potentially caused lysosomal autophagy. Furthermore, exposure to AIE-NPs triggered reactive oxygen species (ROS) production, mitochondrial glutathione (mGSH) depletion and mitochondria dysfunction. The roughest AIE-NPs displayed the strongest cytotoxicity and sequentially led to cell apoptosis. Overall, this study highlighted the critical role of NP nanoscale surface topography, strengthening the understanding and assessment of NP toxicology.

The growing use of plastics has led to microplastics (MPs) being ubiquitously distributed in marine environments. Although previous studies have emphasized MPs as important metal-transport vectors, few have considered the differences between these anthropogenic particles and their coexisting natural counterparts in sequestering metals in seawater. Here, we compared Cu adsorption to pristine and naturally aged MPs (polystyrene and polyethylene) with that to algae particles and sediments and assessed the bioavailability of the adsorbed Cu by a gut juice extraction assay. Adsorption kinetics and isotherms consistently showed that natural particles bound far more Cu to their surfaces than MPs. The rougher surfaces, greater specific surface areas, and lower ζ-potentials of natural particles contributed to their stronger Cu adsorption capacity than pristine or aged MPs. Natural particles also contained more diverse functional groups for binding Cu, with oxygen-containing groups playing a dominant role. Adsorbed Cu on natural particles was less extractable by sipunculan gut juice than that on MPs, indicating their higher Cu affinity. Overall, our study suggests that natural particles outcompete MPs in carrying metals in the water column and transferring them to marine organisms in today’s environmental context. This work provides new insights for assessing the risks of MPs in marine environments.

The silica frustules of diatom are regarded as an important physical defense against predation. While the biogenic silica content of diatoms is a major factor controlling the ingestion rate of copepods, how it affects the three‐dimensional structure and the mechanical properties of the frustules, and consequently copepod grazing, has not been studied. In this study, the diatoms Thalassiosira weissflogiiand Amphora coffeaeformiswere grown under different light intensities to manipulate their cellular biogenic silica contents. This manipulation generated diatom cells with distinct nano‐structures and mechanical strengths. The diatoms were then fed to the copepod Paracalanus pravusto test the effect of biogenic silica contents on copepod feeding. We demonstrated that the copepods preferred the low‐silica cells of T. weissflogii, but showed a preference for the high‐silica cells of A. coffeaeformis. Atomic force microscopy and X‐ray photoelectron spectroscopy analyses revealed that the chemical composition and mechanical properties of diatom frustules varied with silica contents. High silica containing T. weissflogiihad higher frustule elasticity and hardness. In contrast, A. coffeaeformiscontaining more biogenic silica had lower frustule elasticity but silica level had little effect on the hardness of the frustule. Our results indicate that the nano‐structure and chemical properties of the frustules determine the mechanical strength of the diatom frustules. This nanoscale study improves our understanding of the relationship between diatom biogenic silica content and copepod grazing in marine planktonic food webs.

It is crucial to deliver anticancer drugs to target cells with high precision and efficiency. While nanomaterials have been shown to enhance the delivery efficiency once they reach the target, it remains challenging for precise drug delivery to overcome the nonspecific adsorption and off-target effect. To meet this challenge, we report herein the design of a novel DNA nanostructure to act as a DNA nanoscale precision-guided missile (D-PGM) for highly efficient loading and precise delivery of chemotherapeutic agents to specific target cells. The D-PGM consists of two parts: a warhead (WH) and a guidance/control (GC). The WH is a rod-like DNA nanostructure as a drug carrier, whose trunk is a three-dimensionally self-assembled DNA nanoscale architecture from the programmed hybridization among two palindromic DNA sequences in the x–ydimension and two common DNA oligonucleotides in the zdirection, making the WH possess a high payload capacity of drugs. The GC is an aptamer-based logic gate assembled in a highly organized fashion capable of performing cell-subtype-specific recognition via the sequential disassembly, mediated by cell-anchored aptamers. Because of the cooperative effects between the WH and the GC, the GC logic gates operate like the guidance and control system in a precision-guided missile to steer the doxorubicin (DOX)-loaded DNA WH toward target cancer cells, leading to selective and enhanced therapeutic efficacy. Moreover, fluorophores attached to different locations of D-PGM and DOX fluorescence dequenching upon release enable intracellular tracing of the DNA nanostructures and drugs. The results demonstrate that by mimicking the functionalities of a military precision-guided missile to design the sequential disassembly of the GC system in multistimuli-responsive fashion, our intrinsically biocompatible and degradable D-PGM can accurately identify target cancer cells in complex biological milieu and achieve active targeted drug delivery. The success of this strategy paves the way for specific cell identity and targeted cancer therapy.

Background: Highly Active Metastasis Preventing Therapy (HAMPT) is a quardruple drug combination consisting of mifepristone, aspirin, lysine and doxycycline. Objective: Based on our previous study, here, we further proved that HAMPT could effectively and safely prevent colon cancer metastasis. Methods: It was specifically designed for synergistically controlling key cancer metastatic pathways. The dose of HAMPT was designed at lower than the pharmaceutically-recommended dose, and thus the sub-healthy cancer survivors may take HAMPT safely and for a long time for metastasis chemoprevention. Results: HAMPT within its effective concentration range (1-50 μg/mL) showed no cytotoxicity to colon cancer cells HT-29 and CT-26, but significantly inhibited adhesion and invasion of these colon cancer cell lines to human umbilical vascular endothelial cells (HUVECs), and to Matrigel. HAMPT exhibits a good adhesion inhibited ratio, suggesting that it functions primarily by inhibiting adhesion of the cancer cells to HUVECs, rather than killing the cancer cells. At low concentrations, HAMPT also inhibited cancer cell migration. Flow cytometry analysis revealed that HAMPT had no significant effect on cell cycle, but inhibited IL-1β-induced expression of both E-selectin of HUVECs and Sialyl-Lewis X of HT-29. The in vivo experiment showed that HAMPT suppressed metastasis of CT-26 cells to mouse lungs in a dose-dependent manner. In the mouse model, HAMPT showed advantages in preventing metastasis over other combinations. Conclusion: The present study demonstrated that HAMPT is a novel quadruple drug combination that can safely and effectively prevent cancer metastasis.

Four 4-aminoantipyrine Schiffbases HLa, HLb, HLc, HLd and Le were synthesized and characterized from 4-aminoantipyrine and corresponding aromatic aldehydes. The reaction of the Schiffbaes with CuCl2 were studied. And five mononuclear Cu2+ complexes, CuLa.OH, CuLb.OH.H2O, CuLc.OH, CuLd.OH and CuLe.(OH)2. H2O were obtained and characterized by IR spectra,UV-Vis spectra and elemental analysis. The catalytic degradation of acid blue 9 was investigated by UV-Vis spectra, using the five synthetic Schiff base copper complexes as oxidase model compound. It was found that the five complexes all have catalytic effect. The catalytic activity of the three complexes, CuLa.OH, CuLb.OH.H2O and CuLc.OH are better. It was found that the catalytic properties of the three complexes were similar with the enzymatic properties. Then the Km of CuLa.OH, CuLb.OH.H2O and CuLc.OH was deterrmined with Km =1.15×10-2 , 4.79×10-2 and 6.89×10-2 mmol / L, respectively. It is showed that the CuLa.OH, CuLb.OH.H2O and CuLc.OH could be used as oxidase model compounds to catalyze the acid blue 9 degradation. The products of the acid blue 9 degradation was analyzed by HPLC method. It was found the degradation product was maleic acid. The degradation mechanism of the acid blue 9 was deduced. And the catalytic cycle for enzyme model compounds was deduced. Three novel biomimetic catalysts with acid blue 9 degradation properties were obtained, which provides theoretical and experimental supports for a new dye removal technology.

Six benzimidazole derivatives were synthesized and charactrized by IR spectra, 1H-NMR spectra and MS spectra. The coordination reaction of the derivatives with CuCl2. And six novel Cu (II) complexes with the derivatives were prepared and characterized by UV spectra, IR spectra and elemental analysis. The catalytic degradation of methyl orange aqueous solution was investigated using the complexes as catalysis in presence H2O2 by HPLC method and Vis-spectrophotometry. The result of characterization showed that there are four coordination sites around Cu (II) in all complexes, which are respectively occupied by one sulfur atom (from the derivative), one nitrogen atom (from the derivative), one oxygen atom ( from the OH-) and one chlor atom (from the Cl-). The degradation of methyl orange indicated that all the complexes show the properties of enzyme activity. And the main degradation products determined were hydroquinone and maleic acid.

(R,R)-N,N’-di-(4-hydroxylbenzal)-1,2-cyclohexanediamine Schiff base(H2L) was synthesized and characterized by 1H NMR spectra, MS spectra and IR spectra. And the coordination reaction of H2L with chlorate of Cu(II) was studied. The reaction of H2L with CuII salt [CuCl2] generates a new compound, the title compound. The title compound was determined by IR spectra, elemental analysis and single-crystal X-ray diffraction. The title compound belongs to the monoclinic system, space group P2(1), with a = 6.6393(6)Å, b = 24.735(2)Å, c = 8.1128(7)Å, α=90.00 º, β=110.1670(10) º , γ=90.00 º, Z=2, V= 1250.60(19) Å3, Dc=1.382 mg.m-3, µ=1.020mm-1,F（000）=554, R=0.0351 and wR= 0.0887. There are five coordination sites around Cu2+ of the title compound, which are respectively occupied by one oxygen atom from one H2O molecule and four nitrogen atoms from two 1,2-cyclohexanediamine molecules. The Cu atom and four chelating nitrogen atoms are coplanar. There exist rich intra-molecular H-bond and intermolecular H-bond, which result in a three dimensional net.

Since 1991, more than five neuro-genetic disorders have been recognized to be caused by trinucleotide repeat expansions, and the list of such diseases should grow. The diseases are characterized clinically by the phenomenon of anticipation, i.e., worsening of the disease phenotype in successive generations with increasing trinucleotide repeat expansion. The presence of anticipation in familial schizophrenia has been suggested. Several studies have provided supportive evidence that the suceptability locus for schizophrenia is on chromosome 6. Therefore, we analyzed three CAG trinucleotide repeat clones D6S1014, D6S1015, and D6S1058 on chromosome 6, which are polymolphic in 30 families with schizophrenia. No unusually, long alleles that would suggest abnormal expansion of more than 35 trinucleotide repeats were observed for these genes. Also, no statistically significant differences were found between the offspring and parental generations of affected subjects or between the affected and unaffected subjects in families with schizophrenia. © 1997 American College of Neuropsyphopharmacology