Multifunctional Antimonene-Silver Nanocomposites for Ultra-Multi-Mode and Multi-Analyte Sensing, Parallel and Batch Logic Computing, Long-Text Information Protection.

To simulate life's emergent functions, mining the multiple sensing capabilities of nanosystems, and digitizing networks of transduction signals and molecular interactions, is an ongoing endeavor. Here, multifunctional antimonene-silver nanocomposites (AM-Ag NCs) are synthesized facilely and fused for molecular sensing and digitization applications (including ultra-multi-mode and multi-analyte sensing, parallel and batch logic computing, long-text information protection). By mixing surfactant, AM, Ag+ and Sodium borohydride (NaBH4) at room temperature for 5 min, the resulting NCs are comprised of Ag nanoparticles scattered within AM nanosheets and protected by the surfactant. Interestingly, AM-Ag NCs exhibit ultra-multi-mode sensing ability for multiplex metal ions (Hg2+, Fe3+, or Al3+), which significantly improved selectivity (≈2 times) and sensitivity (≈400 times) when analyzing the combined channels. Moreover, multiple sensing capabilities of AM-Ag NCs enable diverse batch and parallel molecular logic computations (including advanced cascaded logic circuits). Ultra-multi-mode selective patterns of AM-Ag NCs to 18 kinds of metal ions can be converted into a series of binary strings by setting the thresholds, and realized high-density, long-text information protection for the first time. This study provides new ideas and paradigms for the preparation and multi-purpose application of 2D nanocomposites, but also offers new directions for the fusion of molecular sensing and informatization.

Sequential-Dependent Synthesis of Bimetallic Silver-Chromium Nanoparticles for Multichannel Sensing, Logic Computing, and 3 in 1 Information Protection.

Bimetallic nanomaterials (BNMs) have been used in sensing, biomedicine, and environmental remediation, but their multipurpose and comprehensive applications in molecular logic computing and information security protection have received little attention. Herein, This synthesis method is achieved by sequentially adding reactants under ice bath conditions. Interestingly, Ag-Cr NPs can dynamically selectively sense anions and reductants in multiple channels. Especially, ClO- can be quantitatively detected by oxidizing Ag-Cr NPs with detection limits of 98.37 nM (at 270 nm) and 31.83 nM (at 394 nm). Based on sequential-dependent synthesis process of Ag-Cr NPs, Boolean logic gates and customizable molecular keypad locks are constructed by setting the reactants as the inputs, the states of the resulting solutions as the outputs. Furthermore, dynamically selective response patterns of the Ag-Cr NPs can be converted into binary strings to exploit molecular crypto-steganography to encode, store, and hide information. By integrating the three dimensions of authorization, encryption, and steganography, 3 in 1 advanced information protection based on Ag-Cr nanosensing system can be achieved, which can enhance the anti-cracking ability of information. This research will promote the development and application of nanocomposites in the field of information security and deepen the connection between molecular sensing and the information world.

Microbial Lipopeptide Supramolecular Self-Assemblies as a Methuosis-Like Cell Death Inducer with In Vivo Antitumor Activity.

Discovering new drugs and improving action mechanisms is a promising strategy to overcome chemotherapy ineffectiveness caused by cancer cell apoptosis resistance. Natural products (like cyclic lipopeptides, CLPs) are potential sources of nonapoptotic cell death inducers and can form diverse supramolecular structures, closely relating to their bioactivities. Herein, it is found for the first time that fatty chain is the key to maintain self-assembled form and antitumor activity of microbial-derived amphiphilic CLP bacillomycin Lb (B-Lb). Compared with B-Lb analogues assemblies without antitumor activity, B-Lb supramolecular self-assemblies (including nanomicelles, nanofibers, giant micrometer rods) can be generated in a multilevel and cross-scale manner and served as a methuosis-like cell death inducer triggered by cytoplasmic vacuolation through macropinocytosis in MDA-MB-231-Luc and MCF-7 cells and in vivo tumor-bearing mice. This study will promote constructing of customized CLP micro-/nanostructures with multipurposes and functions, and boost designing of new antitumor drugs as nonapoptotic cell death modulators based on structure-activity relationship.

Peptide-based system for sensing Pb2+ and molecular logic computing.

Peptides with recognition, assembly, various activities exhibit strong power and application prospects in sensing, material science, biomedicine. However, peptide-based sensing and expanding application is still at an early stage. Herein, a peptide-based sensing and logic system was developed for highly sensitive and selective detection of Pb2+ and implementation of logic operations. Our Pb2+ assay method was ultra-rapid (less than 1 min), direct, simple with detection limit of 0.75 nM. Flexibility and scalability of peptide-based solution system facilitated the execution of sensing and logic operations from simple to complex. This research will not only inspire discovery and comprehensive applications (such as sensing and assembly) of more functional peptides, but also provide more opportunities for development and design of peptide-based systems and molecular information technologies.

Matter, energy and information network of a graphene-peptide-based fluorescent sensing system for molecular logic computing, detection and imaging of cancer stem cell marker CD133 in cells and tumor tissues.

Tumorigenesis, metastasis, and the recurrence of cancer, which may result from the abnormal presence or activation of cancer stem cells (CSCs), are involved in disorders of exchanged matter (biomarkers), energy and information in living organisms. Rapid and sensitive detection and imaging of CSC biomarkers (such as CD133) are helpful for early diagnosis and therapeutic evaluation of tumors. Recently, a preliminary exploration of a few affinity molecules (like peptide-based probes) has just begun for chemical measurements and imaging of CSC biomarker CD133. However, a comprehensive analysis of the matter, energy and information in an artificial molecular system has not been demonstrated and applied to biosensing and disease diagnosis. In this study, a graphene-peptide-based fluorescent sensing system was constructed by utilizing a graphene oxide platform and a CD133-specific recognition peptide and comprehensively analysed with respect to matter (molecular events), energy (fluorescence) and information flow. The molecular event interaction networks in this system were further used to perform molecular logic computing, for the sensitive detection of CSC marker CD133 (with a linear range from 0 to 630 nM and a detection limit of 7.91 nM), and for an application involving targeting the imaging of cells and tumor tissues that highly express CD133 (with a detection limit of 1.1 × 103 cells per mL for CT26 CSCs). The present report will provide more opportunities for the development and design of molecular-level intelligent complex systems and will probably promote the development of artificial intelligent sensing and treatment systems, a molecular-level "Internet of Things", and artificial life.

A comprehensive genomic and growth proteomic analysis of antitumor lipopeptide bacillomycin Lb biosynthesis in Bacillus amyloliquefaciens X030.

Lipopeptides (such as iturin, fengycin, and surfactin) from Bacillus possess antibacterial, antifungal, and antiviral activities and have important application in agriculture and pharmaceuticals. Although unremitting efforts have been devoted to improve lipopeptide production by designing gene regulatory circuits or optimizing fermentation process, little attention has been paid to utilizing multi-omics for systematically mining core genes and proteins during the bacterial growth cycle. Here, lipopeptide bacillomycin Lb from new Bacillus amyloliquefaciens X030 was isolated and first found to have anticancer activity in various cancer cells (such as SMMC-7721 and MDA-MB-231). A comprehensive genomic and growth proteomic analysis of X030 revealed bacillomycin Lb biosynthetic gene cluster, key enzymes and potential regulatory proteins (PerR, PhoP, CcpA, and CsfB), and novel links between primary metabolism and bacillomycin Lb production in X030. The antitumor activity of the fermentation supernatant supplemented with amino acids (such as glutamic acid) and sucrose was significantly increased, verifying the role of key metabolic switches in the metabolic regulatory network. Quantitative real-time PCR analysis confirmed that 7 differential expressed genes exhibited a positive correlation between changes at transcriptional and translational levels. The study not only will stimulate the deeper and wider antitumor study of lipopeptides but also provide a comprehensive database, which promotes an in-depth analysis of pathways and networks for complex events in lipopeptide biosynthesis and regulation and gives great help in improving the yield of bacillomycin Lb (media optimization, genetic modification, or pathway engineering).

The Boolean logic tree of molecular self-assembly system based on cobalt oxyhydroxide nanoflakes for three-state logic computation, sensing and imaging of pyrophosphate in living cells and in vivo.

Sensing of pyrophosphate (PPi) is helpful to better understand many life processes and diagnose various early-stage diseases. However, many traditional reported methods based on artificial receptors for sensing of PPi exhibit some disadvantages including difficulties in designing appropriate binding sites and complicated multi-step assembly/functionalization. Thus, it is significantly important and a big challenge to know how to use a simple molecular self-assembly or an interaction system to solve the above-mentioned limits to achieve the quantitative analysis of specific substances in the system. Based on the natural connection and similarity (such as stimulus responsiveness) between sensing and logic computing, in this study, the Boolean logic tree of molecular self-assembly system based on the cobalt oxyhydroxide (CoOOH) nanoplatform is constructed and applied to organize and connect "plug and play" molecular events (fluorescent dye, acridine orange and anion, PPi). By using molecules as inputs and the corresponding fluorescence signal as the output, the CoOOH-based molecular self-assembly system can be programmed for three-input fluorescent Boolean logic computation, fluorescent three-state logic computation, detection of PPi (linear range from 50 to 6400 nM with a detection limit of 20 nM) and even for imaging in living cancer cells and in vivo (in systems such as Zebrafish and Carassius auratus). Our approach adds a new dimension for expanding molecular logic computing and sensing systems, which will not only provide more opportunities for developing novel logic computing paradigms, but also be helpful in promoting the development and applications of intelligent molecular computing and sensing systems.

Directly repurposing waste optical discs with prefabricated nanogrooves as a platform for investigation of cell-substrate interactions and guiding neuronal growth.

Due to rapid change in information technology, many consumer electronics become electronic waste which is the fastest-growing pollution problems worldwide. In fact, many discarded electronics with prefabricated micro/nanostructures may provide a good basis to fulfill special needs of other fields, such as tissue engineering, biosensors, and energy. Herein, to take waste optical discs as an example, we demonstrate that discarded electronics can be directly repurposed as highly anisotropic platforms for in vitro investigation of cell behaviors, such as cell adhesion, cell alignment, and cell-cell interactions. The PC12 cells cultured on biocompatible DVD polycarbonate layers with flat and grooved morphology show a distinct cell morphology, indicating the topographical cue of nanogrooves plays a key role in guidance of neurites growth. By further monitoring cell morphology and alignment of PC12 cells cultured on the DVD nanogrooves at different differentiation times, we find that cell contact interaction with nanotopographies is dynamically adjustable with differentiation time from initial disorder to final order. This study adds a new dimension to not only solving the problems of supply of materials and fabrication of nanopatterns in neural tissue engineering, but may also offering a new promising way of waste minimization or reuse for environmental protection.

Boolean Logic Tree of Label-Free Dual-Signal Electrochemical Aptasensor System for Biosensing, Three-State Logic Computation, and Keypad Lock Security Operation.

The most serious and yet unsolved problems of molecular logic computing consist in how to connect molecular events in complex systems into a usable device with specific functions and how to selectively control branchy logic processes from the cascading logic systems. This report demonstrates that a Boolean logic tree is utilized to organize and connect "plug and play" chemical events DNA, nanomaterials, organic dye, biomolecule, and denaturant for developing the dual-signal electrochemical evolution aptasensor system with good resettability for amplification detection of thrombin, controllable and selectable three-state logic computation, and keypad lock security operation. The aptasensor system combines the merits of DNA-functionalized nanoamplification architecture and simple dual-signal electroactive dye brilliant cresyl blue for sensitive and selective detection of thrombin with a wide linear response range of 0.02-100 nM and a detection limit of 1.92 pM. By using these aforementioned chemical events as inputs and the differential pulse voltammetry current changes at different voltages as dual outputs, a resettable three-input biomolecular keypad lock based on sequential logic is established. Moreover, the first example of controllable and selectable three-state molecular logic computation with active-high and active-low logic functions can be implemented and allows the output ports to assume a high impediment or nothing (Z) state in addition to the 0 and 1 logic levels, effectively controlling subsequent branchy logic computation processes. Our approach is helpful in developing the advanced controllable and selectable logic computing and sensing system in large-scale integration circuits for application in biomedical engineering, intelligent sensing, and control.

Multimorphological Remoldable Silver Nanomaterials from Multimode and Multianalyte Colorimetric Sensing to Molecular Information Technology.

Inspired by life's interaction networks, ongoing efforts are to increase complexity and responsiveness of multicomponent interactions in the system for sensing, programmable control, or information processing. Although exquisite preparation of single uniform-morphology nanomaterials has been extremely explored, the potential value of facile and one-pot preparation of multimorphology nanomaterials has been seriously ignored. Here, multimorphological silver nanomaterials (M-AgN) prepared by one pot can form interaction networks with various analytes, which can be successfully realized from multimode and multianalyte colorimetric sensing to molecular information technology (logic computing and security). The interaction of M-AgN with multianalytes not only induces multisignal responses (including color, absorbance, and wavelength shift) for sensing metal ions (Cr3+, Hg2+, and Ni2+) but also can controllably reshape its four morphologies (nanodots, nanoparticles, nanorods, and nanotriangles). By abstracting binary relationships between analytes and response signals, multicoding parallel logic operations (including simple logic gates and cascaded circuits) can be performed. In addition, taking advantage of natural concealment and molecular response characteristics of M-AgN nanosystems can also realize molecular information encoding, encryption, and hiding. This research not only promotes the construction and application of multinano interaction systems based on multimorphology and multicomponent nanoset but also provides a new imagination for the integration of sensing, logic, and informatization.

Molecular 'email': Electrochemical aptasensing of fish pathogens, molecular information encoding, encryption and hiding applications.

DNA with data encoding and molecular recognition is rarely used in combination with electrochemistry for multipurpose integrated applications (especially in sensing, information communication and security). Herein, we demonstrated an electrochemical aptasensing, information communication and safety system for detection of fish pathogens (Aeromonas hydrophila or Edwardsiella tarda) and molecular information encryption and hiding. Two fish pathogens can be easily and quickly detected by electrochemistry, respectively, with high selectivity and sensitivity (detection limit lower than 1 cfu/mL) without the need for traditional time-consuming biochemical culturing process. The specific interaction of the probe (DNA aptamer) with targets (pathogens) on the tiny and imperceptible electrochemical platform provides protection for hiding DNA aptamers containing the encoded message, but also offers a foundation for developing of molecular cryptography and steganography. This electrochemical system, which is similar to mail communication, does not record information on paper, but a molecular mail that records information through DNA and reads information using electrochemical sensing, or more precisely, molecular electrochemical mail (namely molecular 'email'). Our study proved that the combination of the recognition and encoding capabilities of DNA aptamers with electrochemistry can open a new door for molecular-level digitization technology. In the future, large-capacity, easy-to-operate, resettable, and flexible molecular crypto-steganography will be developed for molecular cascade communication and control.

A molecular paradigm: "Plug-and-play" chemical sensing and crypto-steganography based on molecular recognition and selective response.

Inspired by information processing and communication in nature based on molecular recognition and structural diversity, ongoing efforts aim to development of artificial molecular or nano-systems for sensing, logic computing, and even data storage and safety. However, due to their preparation/functionalization shortcomings (laborious and time-consuming), poor flexibility and compatibility, and limited paradigm, it is still a big challenge whether simple molecules can be used to achieve comprehensive and universal applications from sensing to information storage and protection. Herein, we for the first time demonstrated a molecular paradigm-computer-like "basic input output system (BIOS)" which can realize "plug-and-play" sensing, information encoding, molecular cryptography, and steganography based on a simple artificial molecule (p-nitrophenol, PNP). Based on its molecular recognition and inherent chemical identities, PNP was utilized for colorimetric detection of multiple metal ions (Hg2+, Fe3+, Al3+, Cr3+) and distinguishing their valence (like Cr3+/Cr6+, Fe3+/Fe2+). Interestingly, PNP can achieve the "plug-and-play" fluorescent expansion of detection channels by directly mixing with fluorescent molecules, indicating that PNP molecule can be served as a molecular BIOS with flexibility and compatibility. Impressively, the selectivity embedded in PNP-based BIOS sensing system can be developed as molecular-level double cryptographic steganography to encode, encrypt and hide specific information (like the content of classical literature). This research not only provides a basic idea for building a molecular paradigm with "plug-and-play" flexibility and compatibility, but also provides ideas for the use of molecular sensing and informatization to open up the digitalization of the molecular world.

Peptide-Based Sensing, Logic Computing, and Information Security on the Antimonene Platform.

Peptides have higher information density than DNA and equivalent molecular recognition ability and durability. However, there are currently no reports on the comprehensive use of peptides' recognition ability and structural diversity for sensing, logic computing, information coding, and protection. Herein, we, for the first time, demonstrate peptide-based sensing, logic computing, and information security on the antimonene platform. The molecular recognition capability and structural diversity (amino acid sequence) of peptides (Pb2+-binding peptide DHHTQQHD as a model) adsorbed on the antimonene universal fluorescence quenching platform were comprehensively utilized to sense targets (Pb2+) and give a response (fluorescence turn-on) and then to encode, encrypt, and hide information. Fluorescently labeled peptides used as the recognition probe and the information carrier were quenched and hidden by the large-plane two-dimensional material antimonene and specifically bound by Pb2+ as the stego key, resulting in fluorescence recovery. The above interaction and signal change can be considered as a peptide-based sensing and steganographic process to further implement quantitative detection of Pb2+, complex logic operation, information coding, encrypting, and hiding using a peptide sequence and the binary conversion of its selectivity. This research provides a basic paradigm for the construction of a molecular sensing and informatization platform and will inspire the development of biopolymer-based molecular information technology (processing, communication, control, security).

Microwave-Assisted Synthesis of Silver Nanoparticles for Multimode Colorimetric Sensing of Multiplex Metal Ions and Molecular Informatization Applications.

Plasmonic materials have been widely used in chemo/biosensing and biomedicine. However, little attention has been paid to the application of plasmonic materials in terms of the transition from molecular sensing to molecular informatization. Herein, we demonstrated that silver nanoparticles (AgNPs) prepared through facile and rapid microwave heating have multimode colorimetric sensing capabilities to different metal ions (Cr3+, Hg2+, and Ni2+), which can be further transformed into interesting and powerful molecular information technology (massively parallel molecular logic computing and molecular information protection). The prepared AgNPs can quantitatively and sensitively detect Cr3+ and Hg2+ in actual water samples. The AgNPs' multimode-guided multianalyte sensing processing was further investigated to construct a series of basic logic gates and advanced cascaded logic circuits by considering the analytes as the inputs and the colorimetric signals (like color, absorbance, wavelength shift) as the outputs. Moreover, the selective responses and molecular logic computing ability of AgNPs were also utilized to develop molecular cryptosteganography for encrypting and hiding some specific information, which proves that the molecular world and the information world are interconnected and use each other. This research not only opens the door for the transition from molecular sensing to molecular informatization but also provides an excellent opportunity for the construction of the "metaverse" of the molecular world.

Genetic Polymorphisms of Long Non-coding RNA Linc00312 Are Associated With Susceptibility and Predict Poor Survival of Nasopharyngeal Carcinoma.

BACKGROUND: Linc00312 is dysregulated in nasopharyngeal carcinoma (NPC) and participates in the initiation and progression of NPC. Our previous studies suggested that linc00312 was able to enhance the sensitivity of NPC cells to irradiation and NPC patients with higher expression of linc00312 was associated with better short-term curative effect and overall survival. The single nucleotide polymorphisms (SNPs) of lncRNAs may influence the disease course and outcome by affecting the expression, secondary structure or function of lncRNAs. However, the role of SNPs in linc00312 on the occurrence and survival of NPC remains unknown. METHODS: We recruited 684 NPC patients and 823 healthy controls to evaluate the association between linc00312 SNPs and NPC susceptibility by using multivariate logistic regression analysis. Kaplan-Meier analysis and Cox proportional hazards regression were applied to assess the effect of linc00312 SNPs on the survival of NPC patients. The relative expression of linc00312 in NPC tissues was determined by real-time PCR. The interaction between linc00312 and mir-411-3p was explored by luciferase reporter assay. In silico prediction of the changes on linc00312 folding structure was conducted by RNAfold WebServer. RESULT: We demonstrated that rs12497104 (G > A) GA genotype carriers had a higher risk than others for suffering from NPC (GA vs GG, OR = 1.437, P = 0.003). Besides, patients with rs12497104 AA genotype showed a poorer overall survival in contrast to GG genotype (AA vs GG, HR = 2.117, P = 0.011). In addition, the heterozygous carriers of rs15734 (G > A) and rs164966 (A > G) were correlated with decreased risk of NPC (GA vs GG, OR = 0.778, P = 0.031; GA vs AA, OR = 0.781, P = 0.033, respectively). We found that the three SNPs might influence the expression of linc00312 in a genotype specific feature. The local centroid secondary structure as well as the minimum free energy of linc00312 were changed following the candidate SNPs alterations. Besides, we revealed that the G to A alteration at rs12497104 disrupted the binding between mir-411-3p and linc00312. CONCLUSION: Our results indicated genetic polymorphisms of linc00312 might serve as potential biomarkers for NPC carcinogenesis and prognosis.

Graphene-Based Steganographically Aptasensing System for Information Computing, Encryption and Hiding, Fluorescence Sensing and in Vivo Imaging of Fish Pathogens.

Inspired by information processing and communication of life based on complex molecular interactions, some artificial (bio)chemical systems have been developed for applications in molecular information processing or chemo/biosensing and imaging. However, little attention has been paid to simultaneously and comprehensively utilize the information computing, encoding, and molecular recognition capabilities of molecular-level systems (such as DNA-based systems) for multifunctional applications. Herein, a graphene-based steganographically aptasensing system was constructed for multifunctional application, which relies on specific molecular recognition and information encoding abilities of DNA aptamers ( Aeromonas hydrophila and Edwardsiella tarda-binding aptamers as models) and the selective adsorption and fluorescence quenching capacities of graphene oxide (GO). Although graphene-DNA systems have been widely used in biosensors and diagnostics, our proposed graphene-based aptasensing system can not only be utilized for fluorescence sensing and in vivo imaging of fish pathogens ( A. hydrophila and E. tarda), but can also function as a molecular-level logic computing system where the combination of matters (specific molecules or materials) as inputs produces the resulting product (matter level) or fluorescence (energy level) changes as two outputs. More importantly and interestingly, our graphene-based steganographically aptasensing system can also serve as a generally doubly cryptographic and steganographic system for sending different secret messages by using pathogen-binding DNA aptamers as information carriers, GO as a cover, and a pair of keys, that is, target pathogen as a public key, the encryption key used to encode or decode a message in DNA as a private key. Our study not only provides a novel nanobiosensing assay for rapid and effective sensing and in vivo imaging of fish pathogens, but also demonstrates a prototype of (bio)molecular steganography as an important and interesting extension direction of molecular information technology, which is helpful in probably promoting the development of multifunctional molecular-level devices or machines.

Highly Tunable and Scalable Fabrication of 3D Flexible Graphene Micropatterns for Directing Cell Alignment.

Patterning graphene allows to precisely tune its properties to manufacture flexible functional materials or miniaturized devices for electronic and biomedical applications. However, conventional lithographic techniques are cumbersome for scalable production of time- and cost-effective graphene patterns, thus greatly impeding their practical applications. Here, we present a simple scalable fabrication of wafer-scale three-dimensional (3D) graphene micropatterns by direct laser tuning graphene oxide reduction and expansion using a LightScribe DVD writer. This one-step laser-scribing process can produce custom-made 3D graphene patterns on the surface of a disk with dimensions ranging from microscale up to decimeter scale in about 20 min. Through control over laser-scribing parameters, the resulting various 3D graphene patterns are exploited as scaffolds for controlling cell alignment. The 3D graphene patterns demonstrate their potential to biomedical applications, beyond the fields of electronics and photonics, which will allow to incorporate flexible graphene patterns for 3D cell or tissue culture to promote tissue engineering and drug testing applications.