Polysaccharide functionalization reduces lipid vesicle stiffness.

The biophysical properties of lipid vesicles are important for their stability and integrity, key parameters that control the performance when these vesicles are used for drug delivery. The vesicle properties are determined by the composition of lipids used to form the vesicle. However, for a given lipid composition, they can also be tailored by tethering polymers to the membrane. Typically, synthetic polymers like polyethyleneglycol are used to increase vesicle stability, but the use of polysaccharides in this context is much less explored. Here, we report a general method for functionalizing lipid vesicles with polysaccharides by binding them to cholesterol. We incorporate the polysaccharides on the outer membrane leaflet of giant unilamellar vesicles (GUVs) and investigate their effect on membrane mechanics using micropipette aspiration. We find that the presence of the glycolipid functionalization produces an unexpected softening of GUVs with fluid-like membranes. By contrast, the functionalization of GUVs with polyethylene glycol does not reduce their stretching modulus. This work provides the potential means to study membrane-bound meshworks of polysaccharides similar to the cellular glycocalyx; moreover, it can be used for tuning the mechanical properties of drug delivery vehicles.

Cavity hairpin ThT-light nucleic acid switches: the construction of label- and enzyme-free sensing and imaging platforms.

Thioflavin T (ThT) is a classical fluorescent dye gaining prominence in current research regarding nucleic acid conformations (NACs). However, most NACs with the ability to excite ThT fluorescent are unique or form in demanding conditions, limiting the extensiveness and depth of ThT application in sensing and imaging. Therefore, this study proposed CGG-AAA mismatched cavity hairpin ThT-light nucleic acid switches (CHTLNAS) with excellent fluorescence excitation over 500-fold higher than spontaneous, 17∼20-fold higher than ssDNA and 2.5∼5-fold higher than complementary duplex. Based on the excellent fluorescence excitation, convenient conformation formation, good sequence programmability, and flexible allosteric ability (known as the Worm-crack pod mechanism mediated by the target), it achieved the label- and enzyme-free detection of tetracycline (TET) and berberine (BB) at the pM level within 10 min. Moreover, it was found enable to realize the sensitive tracking of intracellular carriers at the nM level of ThT entry concentration, and prolongated its cell nuclear-entry time of ThT over 8 h, overcoming the non-specific high background signal interference of ThT in the nuclear region, and expanding the diversified application of ThT in cell biology research. Therefore, CHTLNAS is a more universal, practical tool than G-quadruplex or other kinds of NACs for ThT development and utilization in sensing and imaging platforms.

Thermally and Mechanically Stable Perovskite Artificial Synapse as Tuned by Phase Engineering for Efferent Neuromuscular Control.

The doping of perovskites with mixed cations and mixed halides is an effective strategy to optimize phase stability. In this study, we introduce a cubic black phase perovskite CsyFA(1-y)Pb(BrxI(1-x))3 artificial synapse, using phase engineering by adjusting the cesium-bromide content. Low-bromine mixed perovskites are suitable to improve the electric pulse excitation sensitivity and stability of the device. Specifically, the low-bromine and low-cesium mixed perovskite (x = 0.15, y = 0.22) annealed at 373 K allows the device to maintain logic response even after 1000 mechanical flex/flat cycles. The device also shows good thermal stability up to temperatures of 333 K. We have demonstrated reflex-arc behavior with MCMHP synaptic units, capable of making sensory warnings at high frequency. This compositionally engineered, dual-mixed perovskite synaptic device provides significant potential for perceptual soft neurorobotic systems and prostheses.

Vertically Integrated Monolithic Neuromorphic Nanowire Device for Physiological Information Processing.

This study demonstrates the conceptual design and fabrication of a vertically integrated monolithic (VIM) neuromorphic device. The device comprises an n-type SnO2 nanowire bottom channel connected by a shared gate to a p-type P3HT nanowire top channel. This architecture establishes two distinct neural pathways with different response behaviors. The device generates excitatory and inhibitory postsynaptic currents, mimicking the corelease mechanism of bilingual synapses. To enhance the signal processing efficiency, we employed a bipolar spike encoding strategy to convert fluctuating sensory signals to spike trains containing positive and negative pulses. Utilizing the neuromorphic platform for synaptic processing, physiological signals featuring bidirectional fluctuations, including electrocardiogram and breathing signals, can be classified with an accuracy of over 90%. The VIM device holds considerable promise as a solution for developing highly integrated neuromorphic hardware for healthcare and edge intelligence applications.

Chimeric antigen receptor-modified macrophages ameliorate liver fibrosis in preclinical models.

BACKGROUND & AIMS: Treatments directly targeting fibrosis remain limited. Given the unique intrinsic features of macrophages and their capacity to engraft in the liver, we genetically engineered bone marrow-derived macrophages with a chimeric antigen receptor (CAR) to direct their phagocytic activity against hepatic stellate cells (HSCs) in multiple mouse models. This study aimed to demonstrate the therapeutic efficacy of CAR macrophages (CAR-Ms) in mouse models of fibrosis and cirrhosis and to elucidate the underlying mechanisms. METHODS: uPAR expression was studied in patients with fibrosis/cirrhosis and in murine models of liver fibrosis, including mice treated with carbon tetrachloride, a 5-diethoxycarbonyl-1, 4-dihydrocollidine diet, or a high-fat/cholesterol/fructose diet. The safety and efficacy of CAR-Ms were evaluated in vitro and in vivo. RESULTS: Adoptive transfer of CAR-Ms resulted in a significant reduction in liver fibrosis and the restoration of function in murine models of liver fibrosis. CAR-Ms modulated the hepatic immune microenvironment to recruit and modify the activation of endogenous immune cells to drive fibrosis regression. These CAR-Ms were able to recruit and present antigens to T cells and mount specific antifibrotic T-cell responses to reduce fibroblasts and liver fibrosis in mice. CONCLUSION: Collectively, our findings demonstrate the potential of using macrophages as a platform for CAR technology to provide an effective treatment option for liver fibrosis. CAR-Ms might be developed for treatment of patients with liver fibrosis. IMPACT AND IMPLICATIONS: Liver fibrosis is an incurable condition that afflicts millions of people globally. Despite the clear clinical need, therapies for liver fibrosis are limited. Our findings provide the first preclinical evidence that chimeric antigen receptor (CAR)-macrophages (CAR-Ms) targeting uPAR can attenuate liver fibrosis and cirrhosis. We show that macrophages expressing this uPAR CAR exert a direct antifibrotic effect and elicit a specific T-cell response that augments the immune response against liver fibrosis. These findings demonstrate the potential of using CAR-Ms as an effective cell-based therapy for the treatment of liver fibrosis.

The methyltransferase METTL3 regulates endothelial cell proliferation and inflammation via m6A RNA methylation-mediated TRAF1 expression.

The imbalance of vascular endothelial cell homeostasis is the key mechanism for the progression of many vascular diseases. RNA modification, particularly N6-Methyladenosine (m6A), plays important function in numerous biological processes. Nevertheless, the regulatory function of m6A RNA methylation in endothelial dysfunction remains insufficiently characterized. In this study, we established that the m6A methyltransferase METTL3 is critical for regulating endothelial function. Functionally, depletion of METTL3 results in decreased endothelial cells proliferation, survival and inflammatory response. Conversely, overexpression of METTL3 elicited the opposite effects. Mechanistically, MeRIP-seq identified that METTL3 catalyzed m6A modification of TRAF1 mRNA and enhanced TRAF1 translation, thereby up-regulation of TRAF1 protein. Over-expression of TRAF1 successfully rescued the inhibition of proliferation and adhesion of endothelial cells due to METTL3 knockdown. Additionally, m6A methylation-mediated TRAF1 expression can be reversed by the demethylase ALKBH5. Knockdown of ALKBH5 upregulated the level of m6A and protein level of TRAF1, and also increased endothelial cells adhesion and inflammatory response. Collectively, our findings suggest that METTL3 regulates vascular endothelium homeostasis through TRAF1 m6A modification, suggesting that targeting the METTL3-m6A-TRAF1 axis may hold therapeutic potential for patients with vascular diseases.

Multidimensional Applications and Challenges of Riboswitches in Biosensing and Biotherapy.

Riboswitches have received significant attention over the last two decades for their multiple functionalities and great potential for applications in various fields. This article highlights and reviews the recent advances in biosensing and biotherapy. These fields involve a wide range of applications, such as food safety detection, environmental monitoring, metabolic engineering, live cell imaging, wearable biosensors, antibacterial drug targets, and gene therapy. The discovery, origin, and optimization of riboswitches are summarized to help readers better understand their multidimensional applications. Finally, this review discusses the multidimensional challenges and development of riboswitches in order to further expand their potential for novel applications.

Structural Antagonism-Aided Conformational Regulation Enables an Aptamer-Loop G-Quadruplex Modular Sensor of ß-Lactoglobulin.

A simple, reliable method for identifying ß-lactoglobulin (ß-LG) in dairy products is needed to protect those with ß-LG allergies. A common, practical strategy for target detection is designing simplified nucleic acid nanodevices by integrating functional components. This work presents a label-free modular ß-LG aptasensor consisting of an aptamer-loop G-quadruplex (G4), the working conformation of which is regulated by conformational antagonism to ensure respective module functionality and the related signal transduction. The polymorphic conformations of the module-fused sequence are systematically characterized, and the cause is revealed as shifting antagonistic equilibrium. Combined with conformational folding dynamics, this helped regulate functional conformations by fine-tuning the sequences. Furthermore, the principle of specific ß-LG detection by parallel G4 topology is examined as binding on the G4 aptamer loop by ß-LG to reinforce the G4 topology and fluorescence. Finally, a label-free, assembly-free, succinct, and turn-on fluorescent aptasensor is established, achieving excellent sensitivity across five orders of magnitude, rapidly detecting ß-LG within 22-min. This study provides a generalizable approach for the conformational regulation of module-fused G4 sequences and a reference model for creating simplified sensing devices for a variety of targets.

Aptamer and Thiol Co-Regulated Color-Shifting Fluorophores via Dynamic Through-Bond/Space Conjugation for Constructing Ratiometric RNA Sensor.

Fluorophores with color-shifting characteristics have attracted enormous research interest in the quantitative application of RNA sensors. It reports here a simple synthesis, luminescent properties, and co-transcription ability of de-conjugated triphenylmethane leucomalachite green (LMG). This novel clusteroluminescence fluorophore is rapidly synthesized from malachite green (MG) in reductive transcription system containing dithiothreitol, emitting fluorescence in the UV region through space conjugation. The co-transcribed MG RNA aptamer (MGA) bound to the ligand, resulting in red fluorescence from the through-bond conjugation. Given the equilibrated color-shifting fluorophores, they are rationally employed in a 3WJ-based rolling circle transcription switch, with the target-aptamer acting as an activator to achieve steric allosterism. This one-pot system allows the target to compete continuously for allosteric sites, and the activated transcription switches continue to amplify MGA forward, achieving accurate Aflatoxin 1 quantification at the picomolar level in 1 h. Due to the programmability of this RNA sensor, the design method of target-competitive aptamers is standardized, making it universally applicable.

Construction Strategy of Functionalized Liposomes and Multidimensional Application.

Liposomes are widely used in the biological field due to their good biocompatibility and surface modification properties. With the development of biochemistry and material science, many liposome structures and their surface functional components have been modified and optimized one by one, pushing the liposome platform from traditional to functionalized and intelligent, which will better satisfy and expand the needs of scientific research. However, a main limiting factor effecting the efficiency of liposomes is the complicated environmental conditions in the living body. Currently, in order to overcome the above problem, functionalized liposomes have become a very promising strategy. In this paper, binding strategies of liposomes with four main functional elements, namely nucleic acids, antibodies, peptides, and stimuli-responsive motif have been summarized for the first time. In addition, based on the construction characteristics of functionalized liposomes, such as drug-carrying, targeting, long-circulating, and stimulus-responsive properties, a comprehensive overview of their features and respective research progress are presented. Finally, the paper critically presents the limitations of these functionalized liposomes in the current applications and also prospectively suggests the future development directions, aiming to accelerate realization of their industrialization.

Strain-Induced Photocatalytic H2 Production over BiVO4 in Pure Water without Any Cocatalyst.

In this study, BiVO4 nanosheets (BiVO4-NS) were prepared by a facile hydrothermal method. It is found that sonication-induced strain can effectively promote the H2 production over BiVO4-NS in the presence of pure water without any cocatalysts. With the assistance of the sonication, the H2 production over BiVO4-NS is 1.344 mmol·g-1 after 3 h simulated sunlight irradiation, which is 24.8 times higher than that of BiVO4-NS without sonication (0.054 mmol·g-1). In addition, the products of water oxidation are determined to be hydroxyl radicals and hydrogen peroxide. Moreover, BiVO4-NS also shows obviously enhanced photoactivity than that of the commercially available BiVO4 nanoparticles (BiVO4-C). The improved photoactivity of BiVO4-NS is attributed to the effective charge separation and low charge transfer resistance. The underlying mechanism of sonication-promoted water splitting is investigated by a variety of controlled experiments. The results show that ultrasonic waves can produce obvious strain inside the sample, which results in lattice distortion of BiVO4. Therefore, the conduction band of BiVO4 is obviously negative shifted, which is beneficial for H2 production. In addition, the strain in BiVO4 also produces local polarization of the sample, which effectively promotes the charge transfer and separation process. It is hoped that our study could provide a new strategy for achieving efficient photocatalytic water splitting.

Circulating blood biomarkers correlated with the prognosis of advanced triple negative breast cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can improve survivals of metastatic triple negative breast cancer (mTNBC); however, we still seek circulating blood biomarkers to predict the efficacy of ICIs. MATERIALS AND METHODS: In this study, we analyzed the data of ICIs treated mTNBC collected in Anhui Medical University affiliated hospitals from 2018 to 2023. The counts of lymphocytes, monocytes, platelets, and ratio indexes (NLR, MLR, PLR) in peripheral blood were investigated via the Kaplan-Meier curves and the Cox proportional-hazards model. RESULTS: The total of 50 mTNBC patients were treated with ICIs. High level of peripheral lymphocytes and low level of NLR and MLR at baseline and post the first cycle of ICIs play the predictable role of immunotherapies. Lymphocytes counts (HR = 0.280; 95% CI: 0.095-0.823; p = 0.021) and NLR (HR = 1.150; 95% CI: 1.052-1.257; p = 0.002) are significantly correlated with overall survival. High NLR also increases the risk of disease progression (HR = 2.189; 95% CI:1.085-4.414; p = 0.029). When NLR at baseline ≥ 2.75, the hazard of death (HR = 2.575; 95% CI:1.217-5.447; p = 0.013) and disease progression (HR = 2.189; 95% CI: 1.085-4.414; p = 0.029) significantly rise. HER-2 expression and anti-tumor therapy lines are statistically correlated with survivals. CONCLUSIONS: Before the initiation of ICIs, enriched peripheral lymphocytes and poor neutrophils and NLR contribute to the prediction of survivals.

Synergistic monitoring of PM2.5 and CO2 based on active and passive remote sensing fusion during the 2022 Beijing Winter Olympics.

Green and low-carbon are the keywords of the 2022 Beijing Winter Olympic Games (WOG) and the core of sustainable development. Beijing's P M 2.5 and C O 2 emissions attracted worldwide attention during WOG. However, the complex emission sources and frequently changing weather patterns make it impossible for a single monitoring approach to meet the high-resolution, full-coverage monitoring requirements. Therefore, we proposed an active-passive remote sensing fusion method to address this issue. The haze layer height (HLH) was first retrieved from vertical aerosol profiles measured by our high-spectral-resolution lidar located near Olympic venues, which provides new insights into the nonuniform boundary layer and the residual aerosol aloft above it. Second, we developed a bootstrap aggregating (bagging) method that assimilates the lidar-based HLH, satellite-based AOD, and meteorological data to estimate the hourly P M 2.5 with 1 km resolution. The P M 2.5 at Beijing region, Bird's Nest, and Yanqing venues during WOG was 23.00±18.33, 22.91±19.48, and 16.33±10.49µg/m 3, respectively. Third, we also derived the C O 2 enhancements, C O 2 spatial gradients resulting from human activities, and annual growth rate (AGR) to estimate the performance of carbon emission management in Beijing. Based on the top-down method, the results showed an average C O 2 enhancement of 1.62 ppm with an annual decline rate of 2.92 ppm. Finally, we compared the monitoring data with six other international cities. The results demonstrated that Beijing has the largest P M 2.5 annual decline rate of 7.43µg/m 3, while the C O 2 AGR is 1.46 ppm and keeps rising, indicating Beijing is still on its way to carbon peaking and needs to strive for carbon neutrality.

Granite Extraction Based on the SDGSAT-1 Satellite Thermal Infrared Spectrometer Imagery.

Earth observation by remote sensing plays a crucial role in granite extraction, and many current studies use thermal infrared data from sensors such as ASTER. The challenge lies in the low spatial resolution of these satellites, hindering precise rock type identification. A breakthrough emerges with the Thermal Infrared Spectrometer (TIS) on the Sustainable Development Science Satellite 1 (SDGSAT-1) launched by the Chinese Academy of Sciences. With an exceptional 30 m spatial resolution, SDGSAT-1 TIS opens avenues for accurate granite extraction using remote sensing. This study, exemplified in Xinjiang's Karamay region, introduces the BR-ISauvola method, leveraging SDGSAT-1 TIS data. The approach combines band ratio with adaptive k-value selection using local grayscale statistical features for Sauvola thresholding. Focused on large-scale granite extraction, results show F1 scores above 70% for Otsu, Sauvola, and BR-ISauvola. Notably, BR-ISauvola achieves the highest accuracy at 82.11%, surpassing Otsu and Sauvola by 9.62% and 0.34%, respectively. This underscores the potential of SDGSAT-1 TIS data as a valuable resource for granite extraction. The proposed method efficiently utilizes spectral information, presenting a novel approach for rapid granite extraction using remote sensing TIS imagery, even in scenarios with low spectral resolution and a single data source.

Neuromorphic Gustatory System with Salt-Taste Perception, Information Processing, and Excessive-Intake Warning Capabilities.

Emulation of the process of a biological gustatory system could benefit the reconstruction of sense of taste. Here we demonstrate the first neuromorphic gustatory system that emulates the ability of taste perception, information processing, and excessive-intake warning functions. The system integrates a chitosan-derived ion-gel sensor, SnO2 nanowire artificial synapses, and an effect-executive unit. The system accomplish perception and encoding behaviors for taste stimulation without using complex circuits and multivariate analysis, showing short response delay (<1 s), long taste memory duration (>2 h), and a wide perceptive concentration range (0.02-6 wt % salt solution). Especially, SnO2 NW artificial synapses have extremely small response voltage (1 mV), exceeding the biological level by orders of magnitude, representing so-far the highest sensitivity record. This work provides a promising strategy to develop bioinspired and biointegrated electronics with the intention of mimicking and restoring the functions of biological sensory systems.

Helical Nanofiber Photoelectric Synaptic Devices for an Artificial Vision Nervous System.

Inspired by the helical structure and the resultant exquisite functions of biomolecules, helical polymers have received increasing attention. Here, a series of poly(3-hexylthiophene)-block-poly(phenyl isocyanide) (P3HT-b-PPI) copolymers were prepared using a simple one-pot living polymerization method. Interestingly, the P3HT80-b-PPI30 films were found to have a helical nanofiber structure. The corresponding device has superior optoelectronic properties, such as a broadened spectral response range from the visible band to the deep ultraviolet (DUV) and an approximately 5-fold longer carrier decay time after DUV light stimulation. An energy consumption of 1.44 fJ per synaptic event was obtained, which is the lowest energy consumption achieved so far with DUV light stimulation. The encryption and decryption of images are implemented using an array of devices. Finally, a photoreceptor neural pathway was constructed to achieve early warning for the recognition of the display of harmful light. This research provides an effective strategy for the development of a novel optoelectronic synaptic device.

Mixed-Dimensional Nanoparticle-Nanowire Channels for Flexible Optoelectronic Artificial Synapse with Enhanced Photoelectric Response and Asymmetric Bidirectional Plasticity.

A mixed-dimensional dual-channel synaptic transistor composed of inorganic nanoparticles and organic nanowires was fabricated to expand the photoelectric gain range. The device can actualize the sensitization features of the nociceptor and shows improved responsiveness to visible light. Under electrical pulses with different polarities, the apparatus exhibits reconfigurable asymmetric bidirectional plasticity. Moreover, the devices demonstrate good operational tolerance and mechanical stability, retaining more than 60% of their maximum responsiveness after 100 consecutive/bidirectional and 1000 flex/flat operations. The improved photoelectric response of the device endows a high image recognition accuracy of greater than 80%. Asymmetric bidirectional plasticity is used as punishment/reward in a psychological experiment to emulate the improvement of learning motivation and enables real-time forward and backward deflection (+7 and -25°) of artificial muscle. The mixed-dimensional optoelectronic artificial synapses with switchable behavior and electron/hole transport type have important prospects for neuromorphic processing and artificial somatosensory nerves.

MiR133b-mediated inhibition of EGFR-PTK pathway promotes rAAV2 transduction by facilitating intracellular trafficking and augmenting second-strand synthesis.

Recombinant adeno-associated virus (rAAV) is an extremely attractive vector in the in vivo delivery of gene therapy as it is safe and its genome is simple. However, challenges including low permissiveness to specific cells and restricted tissue specificity have hindered its clinical application. Based on the previous studies, epidermal growth factor receptor-protein tyrosine kinase (EGFR-PTK) negatively regulated rAAV transduction, and EGFR-positive cells were hardly permissive to rAAV transduction. We constructed a novel rAAV-miRNA133b vector, which co-expressed miRNA133b and transgene, and investigated its in vivo and in vitro transduction efficiency. Confocal microscopy, live-cell imaging, pharmacological reagents and labelled virion tracking were used to analyse the effect of miRNA133b on rAAV2 transduction and the underlying mechanisms. The results demonstrated that miRNA133b could promote rAAV2 transduction and the effects were limited to EGFR-positive cells. The increased transduction was found to be a direct result of decreased rAAV particles degradation in the cytoplasm and enhanced second-strand synthesis. ss-rAAV2-miRNA133b vector specifically increased rAAV2 transduction in EGFR-positive cells or tissues, while ss-rAAV2-Fluc-miRNA133b exerted an antitumor effect. rAAV-miRNA133b vector might emerge as a promising platform for delivering various transgene to treat EGFR-positive cell-related diseases, such as non-small-cell lung cancer.

Gut Prevotellaceae-GABAergic septohippocampal pathway mediates spatial memory impairment in high-fat diet-fed ovariectomized mice.

Clarifying the risk factors and mechanisms that contribute to the onset of cognitive impairment following estrogen depletion is essential for improving the quality of life of older females. In the current study, using behavioral tests, 16S rDNA sequencing, in vivo and in vitro electrophysiology, optogenetics and chemogenetics, we found that high-fat diet (HFD)-accelerated impairment of hippocampus-dependent memory, gut microbiota, and hippocampal theta rhythmogenesis in ovariectomized (OVX) mice and fecal microbiota transplantation rescued these phenomena. The identification of fasting-activated medial septal neurons showed that PV+ GABAergic neurons in the medial septal area (MSA) respond to gut sensory signals. Optogenetic activation of septohippocampal PV+ GABAergic fibers (but not cholinergic fibers) significantly rescued hippocampal theta rhythmogenesis and spatial memory in HFD-fed OVX mice. Resistant starch supplementation (RSHFD) rectified the gut Prevotellaceae and considerably alleviated reduced septal gut-responsive neurons, decreased hippocampal theta rhythm, and impaired hippocampus-dependent memory in HFD-fed OVX mice. Furthermore, chemogenetic inhibition of septal PV+ GABAergic neurons reversed the neuroprotective effects of resistant starch supplementation. These findings highlight the notable gut-sensory nature of medial septal PV+ GABAergic neurons. A HFD accelerates estrogen deficiency-induced cognitive impairment by disrupting the gut Prevotellaceae-septo-hippocampal pathway. This study contributes to a better understanding of the precise gut-brain control of cognition and cognitive impairment in postmenopausal females.

An Effective Docking-Guided Strategy for Rational Tailoring of Fluorescent Aptamer Switches of Dimethylindole Red Analogue.

The light-up aptamer-dimethylindole red (DIR) complexes have been applied in biochemistry analysis as promising signal transduction tools. However, the unfavorable repulsions between DIR and the long-sequence aptamer switch hinder the complex's further development, and it is urgent to engineer a feasible and efficient strategy for synchronously and rationally adjusting the DIR chemical structure and the DIR aptamer performance. Herein, we communicate a versatile docking-guided rational tailoring strategy to effectively upgrade a DNA aptamer which specifically turns on the fluorescence of a synthesized amino-functionalized DIR analogue (NH2-DIR). After optimizing with three-level tailoring strategies including molecule docking-guided tailoring, coarse tailoring, and fine tailoring, the NH2-DIR aptamer switch with higher binding affinity and specificity, considerable fluorescence-activation ability, and 40% shortened length was obtained. Integrating the experimental and docking results, the binding mechanism between NH2-DIR and the tailored aptamer was deciphered via three types of interactions.