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Page 2 of 25                        Zhong et al. Chem Synth 2023;3:27  https://dx.doi.org/10.20517/cs.2023.15

               Keywords: DNA nanotechnology, dissipative, far-from-equilibrium, signaling dynamic, protocell




               INTRODUCTION
               Life, which evolved from non-living components, represents the most sophisticated self-organization
                              [1,2]
               system in nature . Even the simplest unicellular systems consist of multiple components that exhibit
               spatiotemporal reactions and interactions, giving these systems living properties and functionalities . As a
                                                                                                    [3]
               unique natural phenomenon, the prominent features of life entirely differ from those of non-living systems.
               For example, living systems can sense and process environmental signals to self-organize their structure and
               self-regulate their functionalities, which enable them to survive change-induced events . Such fascinating
                                                                                         [4-6]
               features have inspired scientists from various disciplines. Recently, chemists have attempted to analyze and
                                                             [7]
               comprehend such living features at the molecular level . From a chemical perspective, living characteristics
               are not only determined by the nature of the components but also by the nonlinear reaction and interaction
               networks present in living systems [8-10] . When it comes to understanding and manipulating living systems, it
               is essential to consider the comprehensive study of nonlinear molecule interaction networks at a system
               level, known as systems chemistry. This includes the organization and dynamics of molecular networks, the
               emergence of network-guided properties and functions, and the operation of critical biological processes
               through networks [11-16] .


               As a critical biological network in living systems, signaling dynamic networks determine the conversion of
               environmental signals into cellular activities . These networks are essential in adaptation , regulation ,
                                                                                            [18]
                                                                                                       [19]
                                                     [17]
               and morphogenesis . By sensing, connecting, and dynamically regulating signaling transducers in
                                [20]
               networks, external signals such as light , temperature , pH changes , and chemical inputs  can be
                                                  [21]
                                                                             [23]
                                                                                                 [24]
                                                                [22]
               transduced into corresponding biological signals in living systems. Diverse natural transformations in living
                                                                                          [25]
                                                                                                       [26]
               systems  operate  through  signaling  dynamic  networks,  including  feedback , feedforward ,
               intercommunication , signal propagation , oscillation , steady-state transition , and more. By further
                                                   [28]
                                                                                     [30]
                                                               [29]
                                 [27]
               integrating collective biological transformation processes, organisms could demonstrate adaptivity and
               autonomy during environmental communication [31,32] . Therefore, from a systems chemistry perspective,
               living characteristics can be regarded as emerging properties and functionalities that arise from complex
               dynamic networks.
               The rational design of artificial systems that mimic the functions of living systems has been at the forefront
               of chemistry [14,33,34] . Benefiting from the development of biological understanding, molecular engineering,
               and supramolecular self-assembly, chemists have started synthesizing artificial dynamic networks to mimic
                                               [35]
               natural signaling dynamic networks . Various chemical networks were reported, including cascaded
               signaling networks , self-replicating  and signal-amplifying networks , constitutional dynamic networks
                                                                           [38]
                                              [37]
                               [36]
               and libraries , etc. However, there is still a long way to go in creating artificial systems that exhibit the
                          [39]
               major living characteristics of living systems, where multi-network systems can function like molecular
               intelligence, revealing sufficient reactivity, autonomy, adaptability, sociability, and evolvability.
               Although nucleic acids are known as the building blocks of life, they are also modular and versatile motifs
               that have recently been used to construct sophisticated dynamic networks [35,40,41] . The well-characterized
               nature of DNA base-pairing makes it easy to control their self-assembly processes while also providing
               versatile means to reconfigure switchable DNA structures. These include pH-responsive C-G·C  or T-A·T
                                                                                                 +
                                                              [43]
                      [42]
               triplexes  and cytosine-rich strands into i-motif forms , fuel/anti-fuel strands-driven strand displacement
                       [44]
               reactions , and more. In addition, the nucleic acid sequences encode substantial structural and functional
                                                                                                       [45]
               information,  such  as  the  sequence-specific  recognition  of  low-molecular-weight  ligands ,
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