Nanozymes are a class of nanomaterials with biocatalytic function and enzyme-like activity, whose advantages include high stability, low cost, and mass production. They can catalyze the substrates of natural enzymes based on specific nanostructures and serve as substitutes for natural enzymes. Their applied research involves a wide range of fields such as biomedicine, environmental governance, agriculture, and food. Molecular logic gates are a new cross-disciplinary discipline, which can simulate the function of silicon circuits on a molecular scale, perform single or multiple input logic operations, and generate logic outputs. A molecular logic gate is a binary operation that converts an input signal into an output signal according to the rules of Boolean logic, generating two signals, a high level, and a low level. The high and low levels represent the \"true\" and \"false\" values of the logic gates, and their outputs correspond to \"l\" and \"0\" of the molecular logic gates, respectively. The combination of nanozymes and logic gates is a novel and attractive research direction, and the cross-application of the two brings new opportunities and ideas for various fields, such as the construction of efficient biocomputers, intelligent drug delivery systems, and the precise diagnosis of diseases. This review describes the application of logic gates based on nanozymes, which is expected to provide a certain theoretical foundation for researchers\' subsequent studies.

Molecular logic gates are information processing devices that can respond to environmental signals and produce a readable output in response through Boolean logic operations. Molecules with these properties have been used to build smart sensors and therapeutic agents. In this work, dual enzyme-responsive molecular AND logic gate is developed with the intention to discriminate various combinations of enzyme level and/or activity. A resorufin-based sensor is substituted with self-immolative tyrosinase recognition site, 3-hydroxy benzyl group. The Hydroxyl group is protected with acetyl moiety which decreases the affinity of the enzyme. When both tyrosinase and esterase are present in the solution, the acetyl group is removed by the latter enzyme, allowing the former to recognise the ligand. Oxidation of the ligand by tyrosinase triggers self-immolative cleavage of the substitution, leading to almost 70 fold enhancement in fluorescence. When single enzyme is applied, there is no significant change in the emission intensity overall, an AND logic gate is constructed. Selectivity and Michaelis-Menten kinetics of the sensor is analysed. Smart molecular probes can contribute to the research on the development of biosensors that can discriminate diseases having characteristic combinations of enzyme activities.

Chemical Artificial Intelligence (CAI) is a brand-new research line that exploits molecular, supramolecular, and systems chemistry in wetware (i.e., in fluid solutions) to imitate some performances of human intelligence and promote unconventional robotics based on molecular assemblies, which act in the microscopic world, otherwise tough to be accessed by humans. It is undoubtedly worth spreading the news that AI researchers can rely on the help of chemists and biotechnologists to reach the ambitious goals of building intelligent systems from scratch. This article reports the first attempt at building a Chemical Artificial Intelligence knowledge map and describes the basic intelligent functions that can be implemented through molecular and supramolecular chemistry. Chemical Artificial Intelligence provides new tools and concepts to mimic human intelligence because it shares, with biological intelligence, the same principles and materials. It enables peculiar dynamics, possibly not accessible in software and hardware domains. Moreover, the development of Chemical Artificial Intelligence will contribute to a deeper understanding of the strict link between intelligence and life, which are two of the most remarkable emergent properties shown by the Complex Systems we call biological organisms.

Over the last few years, the development of fluorescent probes has received considerable attention. Fluorescence signaling allows noninvasive and harmless real-time imaging with great spectral resolution in living objects, which is extremely useful for modern biomedical applications. This review presents the basic photophysical principles and strategies for the rational design of fluorescent probes as visualization agents in medical diagnosis and drug delivery systems. Common photophysical phenomena, such as Intramolecular Charge Transfer (ICT), Twisted Intramolecular Charge Transfer (TICT), Photoinduced Electron Transfer (PET), Excited-State Intramolecular Proton Transfer (ESIPT), Fluorescent Resonance Energy Transfer (FRET), and Aggregation-Induced Emission (AIE), are described as platforms for fluorescence sensing and imaging in vivo and in vitro. The presented examples are focused on the visualization of pH, biologically important cations and anions, reactive oxygen species (ROS), viscosity, biomolecules, and enzymes that find application for diagnostic purposes. The general strategies regarding fluorescence probes as molecular logic devices and fluorescence-drug conjugates for theranostic and drug delivery systems are discussed. This work could be of help for researchers working in the field of fluorescence sensing compounds, molecular logic gates, and drug delivery.

Developing activatable fluorescent probes with superlative fluorescence enhancement factor (F/F0 ) to improve the signal-to-noise (S/N) ratio is still an urgent issue. \"AND\" molecular logic gates are emerging as a useful tool for enhanced probes selectivity and accuracy. Here, an \"AND\" logic gate is developed as super-enhancers for designing activatable probes with huge F/F0 and S/N ratio. It utilizes lipid-droplets (LDs) as controllable background input and sets the target analyte as variable input. The fluorescence is tremendously quenching due to double locking, thus an extreme F/F0 ratio of target analyte is obtained. Importantly, this probe can transfer to LDs after a response occurs. The target analyte can be directly visualized through the spatial location without a control group. Accordingly, a peroxynitrite (ONOO- ) activatable probe (CNP2-B) is de novo designed. The F/F0 of CNP2-B achieves 2600 after reacting with ONOO- . Furthermore, CNP2-B can transfer from mitochondria to lipid droplets after being activated. The higher selectivity and S/N ratio of CNP2-B are obtained than commercial probe 3\'-(p-hydroxyphenyl) fluorescein (HPFin vitro and in vivo. Therefore, the atherosclerotic plaques at mouse models are delineated clearly after administration with in situ CNP2-B probe gel. Such input controllable \"AND\" logic gate is envisioned to execute more imaging tasks.

Exploring intelligent fluorescent materials with high reliability and precision to diagnose diseases is significant but remains a great challenge. Herein, based on coordination post-synthetic modification, a Tb3+ functionalized ME-PA (Tb@1) is prepared, which can emit brilliant green fluorescence through ligand-to-mental charge transfer-assisted energy transfer (LMCT-ET) process from ME-PA to Tb3+ ions. Tb@1 can simultaneously distinguish Tryptophan (Try) and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA), two effective indicators for depression, in ratio and colorimetric mode. And this sensor behaves the advantages of high efficiency and sensitivity, as well as excellent reusability and anti-interference. The PET process from ME to Try and 5-HIAA, and the competitive absorption between analytes and Tb@1 may be relevant to sensing mechanism. In realistic serum or urine environment, the detection limits of Tb@1 for Try and 5-HIAA are 0.0183 and 0.0149 mg L-1 respectively. Moreover, in conjunction with back propagation neural network (BPNN), two dual-output molecular logic gates that can be calculated circularly are further designed, which realizes intelligent control of the electronic component to identify the existence of two biomarkers and judge their concentrations from fluorescence images. This work offers a novel approach to modulate logic circuits based on ML-assisted HOF fluorescent sensor, with promising application for a precise and pictorial depression diagnosis.

Ethyl(hydroxyethyl)cellulose (EHEC) and a silica-based xerogel (SBX) were functionalized with a (18-crown-6)-styrylpyridine precursor (1) to obtain the modified polymers EHEC-1 and SBX-1, respectively. Films were obtained and the resulting materials were used as fluorogenic devices for the detection of Hg2+ in water. The films produced from EHEC-1 showed high water retention, making it difficult to apply as a reusable optical chemosensor. Since SBXs are recognized in the literature for their hydrophobicity, a hybrid film composed of EHEC and SBX-1 which did not show water retention was produced and characterized. This system showed rapid response time, outstanding selectivity compared to several other studied metal ions, and sensitivity for the detection of Hg2+ in water. The detection limit for this material using fluorescence technique was 2 ppb (∼10-8 mol L-1). The reversibility of the complex formed between EHEC-SBX-1 film and Hg2+ was demonstrated by the addition of cysteine to the medium. The result obtained also allowed the assembly of INHIBIT and IMPLICATION molecular logic gates, using Hg2+ and cysteine as inputs. The results described in this article have important significance in the development of novel reversible fluorogenic chemosensors and adsorbent materials for the effective removal of Hg2+ ions.

In current work, with elaborate designs of G-quadruplex containing \"Y\" junction structures, we demonstrate the construction of several new and label-free electrochemical logic gate operations (OR, AND, NOR, and NAND) by defining two distinct biomolecules, human 8-oxo-7,8-dihydroguanine DNA glycosylase 1 (hOGG1) and microRNA-141 (miRNA-141), as the inputs. The \"Y\" junction structures are immobilized onto the surface of gold electrode as the signal transduction platform. The presence of the input molecules with different combinations can alter the \"Y\" junction structures to disrupt the formation of the complete G-quadruplexes via 8-oxoG-site specific cleavage and miRNA-141-triggered displacement of the \"Y\" junctions. Subsequent association of hemin with the G-quadruplex sequences thus yields significant current variation outputs upon electrochemical reduction of hemin on the electrode, leading to the successful function of different logic operations without the involvement of labeling the DNA sequences with electro-active species. Featured with the advantages of multiple logic operations with distinct inputs and the label-free electrochemical format, such molecular logic gates can potentially provide promising opportunities for the development of simple and robust biological logic gates for various applications.

The increasing demand for large-scale integrated logic systems urges the development of multireadout molecular logic gates. Especially, it is of great significance to explore dual-readout logic devices with both fluorescence (FL) and magnetic resonance (MR) signals as measurable outputs, since the signal combination of FL/MR might render molecular logic devices better practicality in biomedical applications. In this study, holmium(III)-doped carbon nanodots (Ho-CDs), which exhibited pH-responsive behaviors in both FL and MR signals, were synthesized by a facile one-pot pyrolysis method. When triggered by H+, Fe3+, or Fe2+, the Ho-CDs served as a switch for both FL and MR signals, leading to dual-readout and multiaddressable logic gates. A series of elementary Boolean operations including YES, NOT, OR, NOR, XOR, PASS 0, and INH have been successfully demonstrated by varying the chemical inputs of H+/Fe3+/Fe2+. More importantly, multilevel integrative Boolean operations with higher functions (NOR-INH and MR (XOR + INH)-OR), which realize the concatenation of different logic gates, have also been successfully demonstrated. This study may pave an avenue to design multilevel, dual-readout molecular logic systems with better operation stability, which hold great potential for biomedical applications in the future.

The widespread use of antibiotics caused severe problems of antibiotic residues in foodstuffs and water, posing a serious threat to public health and thus urging the development of sensitive, selective, and rapid detection methods for antibiotics. In this study, a fluorescence resonance energy transfer (FRET)-based system is developed for the multiplexed analysis of chloramphenicol (CAP) and streptomycin (Strep) with detection limits of 2.51 and 8.69μg l-1, respectively. The FRET-based system consists of Cy3-tagged anti-CAP aptamer-conjugated gold nanoparticles (AuNPs) (referred to as AuNPs-AptCAP) and Cy5-tagged anti-Strep aptamer-conjugated AuNPs (referred to as AuNPs-AptStrep). In addition, AuNPs-AptCAP and AuNPs-AptStrep have been demonstrated to serve as signal transducers for implementing a series of logic operations such as YES, NOT, INH, OR, (2-4)-Decoder and even more complicated multi-level logic gates (OR-INH). Based on the outputs of logic operations, it could be figured out whether targeted analytes were present or not, thus enabling multiplex sensing and evaluation of pollution status. This proof of concept study might provide a new route for the enhanced sensing performance to distinguish different pollution status as well as the design of molecular mimics of logic elements to demonstrate better applicability.