Modular cascaded amplification of cellular sensor signal. A typical cellular sensor can be abstracted as a three-stage processor comprising a sensing module that recognizes and transduces external signals into intracellular transcriptional signals, a computing module that modulates the transduced sensor signals, and an output actuating module that executes physiological responses (Fig. 1a) [1][2][3]32 . Our modular signal amplifying methodology integrates three synergistic signal amplification strategies by manipulating the first two modules step-by-step.
Transcriptional regulation by nuclease-deficient CRISPR/Cas is a popular and valuable tool for routine control of gene expression. CRISPR interference in bacteria can be reliably achieved with high efficiencies. Yet, options for CRISPR activation (CRISPRa) remained limited in flexibility and activity because they relied on σ
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promoters. Here we report a eukaryote-like bacterial CRISPRa system based on σ
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-dependent promoters, which supports long distance, and hence multi-input regulation with high dynamic ranges. Our CRISPRa device can activate σ
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-dependent promoters with biotechnology relevance in non-model bacteria. It also supports orthogonal gene regulation on multiple levels. Combining our CRISPRa with dxCas9 further expands flexibility in DNA targeting, and boosts dynamic ranges into regimes that enable construction of cascaded CRISPRa circuits. Application-wise, we construct a reusable scanning platform for readily optimizing metabolic pathways without library reconstructions. This eukaryote-like CRISPRa system is therefore a powerful and versatile synthetic biology tool for diverse research and industrial applications.
Though evaporation‐driven electricity generation has emerged as a novel eco‐friendly energy and attracted intense interests, it is typically demonstrated in pure water or a very low salt concentration. Integrating evaporation‐driven electricity generation and solar steam desalination simultaneously should be more promising. Herein, a polyaniline coated metal‐organic frameworks (MOFs) nanorod arrays membrane is synthesized which inherits the merits of both polyaniline and MOFs, demonstrating nice stability, good interfacial solar steam desalination, and evaporation‐driven electricity generation. Moreover, an integrated system based on this hybrid membrane achieves good interfacial solar‐heating evaporation and prominently enhanced evaporation‐driven electricity generation under one sun. Notably, the realization of effective seawater desalination and efficient evaporation‐driven electricity generation simultaneously by the non‐carbon‐based materials is reported for the first time, which provides a new alternative way for cogenerating both freshwater and electricity by harvesting energy from seawater and solar light.
Periodontitis is a bacterial infectious disease leading to the loss of periodontal supporting tissues and teeth. The current guided tissue regeneration (GTR) membranes for periodontitis treatments cannot effectively promote tissue regeneration for the limited antibacterial properties and the excessively fast degradation rate. Besides, they need extra tailoring according to variform defects before implantation, leading to imprecise match. This study proposed an injectable sodium alginate hydrogel composite (CTP-SA) doped with cubic cuprous oxide (Cu 2 O) and polydopaminecoated titanium dioxide (TiO 2 @PDA) nanoparticles for GTR. Inspired by the gelation process of the jelly, the phase change (liquid to solid) of CTP-SA after injection could automatch variform bone defects. Meanwhile, CTP-SA exhibited broad-spectrum antibacterial capabilities under blue light (BL) irradiation, including Streptococcus mutans (one of the most abundant bacteria in oral biofilms). Moreover, the reactive oxygen species released under BL excitation could accelerate the oxidation of Cu + to Cu 2+ . Afterward, osteogenesis could be enhanced through two factors simultaneously: the stimulation of newly formed Cu 2+ and the photothermal effect of CTP-SA under near-infrared (NIR) irradiation. Collectively, through this dual-light (blue and NIR) noninvasive regulation, CTP-SA could switch antibacterial and osteogenic modes to address requirements of patients at different healing stages, thereby realizing the customized GTR procedures.
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