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Engineering bacteria can achieve targeted and controllable cancer therapy using synthetic biology technology and the characteristics of tumor microenvironment. Besides, the accurate tumor diagnosis and visualization of the treatment process are also vital for bacterial therapy. In this paper, a light control engineered bacteria system based on upconversion nanoparticles (UCNP)-mediated time-resolved imaging (TRI) was constructed for colorectal cancer theranostic and therapy. UCNP with different luminous lifetimes were separately modified with the tumor targeting molecule (folic acid) or anaerobic bacteria (Nissle 1917, EcN) to realize the co-localization of tumor tissues, thus improving the diagnostic accuracy based on TRI. In addition, blue light was used to induce engineered bacteria (EcN-pDawn-φx174E/TRAIL) lysis and the release of tumor apoptosis-related inducing ligand (TRAIL), thus triggering tumor cell death.

The discovery of the gut-brain axis has proven that brain functions can be affected by the gut microbiota's metabolites, so there are significant opportunities to explore new tools to regulate gut microbiota and thus work on the brain functions. Meanwhile, engineered bacteria as oral live biotherapeutic agents to regulate the host's healthy homeostasis have attracted much attention in microbial therapy. However, whether this strategy is able to remotely regulate the host's brain functioniin vivo/ihas not been investigated. Here, we engineered three blue-light-responsive probiotics as oral live biotherapeutic agents. They are spatiotemporally delivered and controlled by the upconversion optogenetic micro-nano system. This micro-nano system promotes the small intestine targeting and production of the exogenousiL. lactis/iin the intestines, which realizes precise manipulation of brain functions including anxiety behavior, Parkinson's disease, and vagal afferent. The noninvasive and real-time probiotic intervention strategy makes the communiation from the gut to the host more controllable, which will enable the potential for engineered microbes accurately and effectively regulating a host's health.

For the biomedical application of engineered bacteria, strictly regulating the function of engineered bacteria has always been the goal pursued. However, the existing regulation methods do not meet the needs of the

Subcutaneous administration of sustained-release formulations is a common strategy for protein drugs, which avoids first pass effect and has high bioavailability. However, conventional sustained-release strategies can only load a limited amount of drug, leading to insufficient durability. Herein, we developed microcapsules based on engineered bacteria for sustained release of protein drugs. Engineered bacteria were carried in microcapsules for subcutaneous administration, with a production-lysis circuit for sustained protein production and release. Administrated in diabetic rats, engineered bacteria microcapsules was observed to smoothly release Exendin-4 for 2 weeks and reduce blood glucose. In another example, by releasing subunit vaccines with bacterial microcomponents as vehicles, engineered bacterial microcapsules activated specific immunity in mice and achieved tumor prevention. The engineered bacteria microcapsules have potential to durably release protein drugs and show versatility on the size of drugs. It might be a promising design strategy for long-acting in situ drug factory.

Engineered anaerobic bacteria known as live biotherapeutic products (LBPs) have shown great advances in cancer therapy. One advantage of anaerobic bacteria as drug carrier is that it spontaneously target to tumor and persistently release anti-tumor factors. To realize effective anti-cancer therapeutics, one essential premise is to improve the controllability of treatment. Here, we designed near-infrared (NIR)-light responsive bacteria as anti-tumor agent, which is based on a blue-light responsive module and upconversion nanoparticles. The upconversion nanoparticles converted external NIR light to local blue light to noninvasively activate blue-light responsive module (EL222) in engineered LBPs. The activated LBPs then produce tumor necrosis factor α (TNFα) for precise tumor ablation. In vitro and in vivo results have proven that this engineered NIR-light-responsive bacteria could efficiently inhibit tumor growth. We anticipate that this controllable and safe bacteria-based therapy can facilitate the application of LBPs to accurately and effectively regulate diseases.

Summary Recombinant bacterial colonization plays an indispensable role in disease prevention, alleviation, and treatment. Successful application mainly depends on whether bacteria can efficiently spatiotemporally colonize the host gut. However, a primary limitation of existing methods is the lack of precise spatiotemporal regulation, resulting in uncontrolled methods that are less effective. Herein, we design upconversion microgels (UCMs) to convert near-infrared light (NIR) into blue light to activate recombinant light-responsive bacteria (Lresb) in vivo, where autocrine “functional cellular glues” made of adhesive proteins assist Lresb inefficiently colonizing the gut. The programmable engineering platform is further developed for the controlled and effective colonization of Escherichia coli Nissle 1917 (EcN) in the gut. The colonizing bacteria effectively alleviate DSS-induced colitis in mice. We anticipate that this approach could facilitate the clinical application of engineered microbial therapeutics to accurately and effectively regulate host health.

In this work, we demonstrate boron nitride whisker @ graphene (BN@GE) nanohybrids with a unique morphology as a thermally conductive filler for improving the thermal conductivity of a polymer matrix. In this structure, GE sheets were applied to insulating hexagonal boron nitride (BN) whiskers via a simplified method to ensure the sheets were well separated when used in epoxy composites. The addition of GE to produce the BN@GE hybrids was found to reduce the length of the BN whiskers. In addition, separation of the sheets enhanced the three-dimensional thermally conductive networks within the composite, which improved the thermal conductivity and significantly enhanced the dielectric constant. Furthermore, the implanted insulating network of BN inhibited the charge carrier mobility on the well-separated sheets via GE fixation on the BN whiskers, and resulted in a low dielectric loss. As a result, the epoxy composite containing 40 wt% BN@GE-15 hybrid filler exhibited a thermal conductivity, dielectric constant, and ultra-low dielectric loss of 1.26 W m−1 K−1, 12.7, and 0.0051, respectively. We expect this uniquely structured hybrid filler will be suitable for the fabrication of thermal interface materials with high thermal conductivities and low dielectric losses.

This paper presents a new spiral inductor based on substrate integrated suspended line (SISL) technology. SISL is a new type of transmission line, which has many merits, such as low loss, low dispersion, and self-packaging. New series of spiral inductors based on this advanced SISL platform is proposed and modeled in this paper. SISL to microstrip transition is designed for the measurement of the SISL inductor, and an open-short deembedding method is introduced for the accurate extraction of inductor network parameters. A $\pi$ equivalent circuit model is applied for modeling of the SISL inductor and new double-sided SISL (DSISL) inductor, and the accurate empirical expression of inductance $L$ , peak quality factor $Q_{\mathrm {max}}$ , and self-resonance frequency are given. The typical relative error of each expression is less than 8%. Finally, a new DSISL inductor with patterned substrate is proposed, which can significantly improve the quality factor up to 40%. Simulation and measurement results show good agreement.

This paper presents a slow-wave rat-race coupler using substrate integrated suspended line (SISL) technology. Double-sided interconnected strip line (DSISL) is utilized to further reduce the loss of the suspended line circuit. Using the DSISL concept, a slow-wave structure based on modified meander line configuration is proposed. Formed by simple circuit topology with only three parameters of one unit cell, the characteristic impedance and slow-wave factor of the proposed slow-wave DSISL can be controlled separately. Utilizing the proposed slow-wave DSISL, a rat-race coupler at 1.5 GHz has been designed and fabricated by standard printed circuit board process. A 90.5% size reduction is achieved, and the fractional bandwidth is 26.5%. Benefiting from SISL technology, the proposed slow-wave rat-race coupler is self-packaged and has advantages of low cost and light weight.

The pagC gene is ubiquitously distributed in Salmonella, but there is limited information regarding its function. Pullorum disease (PD) is a septicemic disease caused by Salmonella Pullorum, which also harbors the pagC gene. In this study, we constructed an S. Pullorum pagC gene deletion strain and its complemented strain. First, we confirmed that the pagC gene does not participate in bacterial growth regulation or environmental pH adaptation. Interestingly, the results of subsequent analyses indicated that the pagC gene defect led to increased bacterial colonization in the intestine (especially in the cecum) and increased biofilm formation, while the number of outer-membrane vesicles (OMVs) in the bacterial culture decreased. Purified OMVs were able to reduce S. Pullorum biofilm formation in vitro. In addition, the results of a mass spectrometry analysis of purified OMVs indicated that some enzymes harbored by OMVs may be involved in biofilm degradation. Based on these results, we conclude that deletion of the pagC gene leads to reduced S. Pullorum OMVs production, which subsequently promotes biofilm stability, increases bacterial colonization in the intestine, and potentially inhibits the switch from sessile to planktonic growth.

A novel transition from substrate integrated suspended line (SISL) to conductor backed coplanar waveguide (CBCPW) is proposed in this letter. The proposed transition utilizing the standard PCB techniques eliminates the drawbacks of the traditional suspended circuits and integrates the suspended circuits effectively. The new transition is a self-packaged system verified by both simulation and experiment results. Back-to-back transition structure has insertion loss of less than 0.6 dB and return loss of better than 15 dB from dc to 8 GHz.

This paper presents a novel self-packaged high quality factor spiral inductor based on substrate integrated suspended line technology. Suspended substrate are hollowed in specific shape for reducing the dielectric substrate loss. Double-sided interconnected stripline is used for diminishing the metal ohmic loss. Simulation and measurement results demonstrate that the double-sided interconnected spiral inductor with patterned substrate can improve inductor quality factor up to 40%.

This paper proposes a spiral inductor based on substrate integrated suspended line (SISL) technology. Short-open de-embedding method is used for the parameter extraction, a physical model is established for SISL inductor. The measurement and simulation results confirm that the equivalent-circuit can accurately characterizes the behavior of the spiral inductor.

This paper proposes a low loss branch line coupler based on substrate integrated suspended line (SISL) technology and double-sided interconnected strip line (DSISL). Compared with conventional suspended line structure, the proposed SISL coupler has the advantages of self-packaging, compact size and low loss. DSISL is introduced in the design to further reduce the losses. A branch line SISL coupler has been designed and fabricated by printed circuit board technology. Simulation results and measurement results show great agreement.

A novel substrate integrated suspended microstrip line (SISML) patch antenna array is demonstrated to achieve relatively high gain and high efficiency at 24 GHz band. Compared with traditional suspended stripline structure, the proposed antenna array has compact size and high efficiency. The proposed antenna array is designed by using multilayer printed circuit board (PCB) technology. The designed antenna array has 4 antenna elements while demonstrates gain of greater than 13.5dB and efficiency of better than 85% at 22.9 GHz-24.9 GHz with an overall size of 45.3 mm × 51 mm × 98mil.