lincRNA-p21 was downregulated in HCC and lincRNA-p21 overexpression contributed to the inhibition of tumor invasion through mediating Notch signaling induced EMT.

Photodynamic therapy (PDT) holds great promise as a noninvasive and selective cancer therapeutic treatment in preclinical research and clinical practice; however, it has limited efficacy in the ablation of deep-seated tumor because of hypoxia-associated circumstance and poor penetration of photosensitizers to cancer cells away from the blood vessels. To tackle the obstacles, we propose a therapeutic strategy that synergizes upconversion nanophotosensitizers (UNPSs) with hyperbaric oxygen (HBO) to remodel the extracellular matrix for enhanced photodynamic cancer therapy. The UNPSs are designed to have an Nd-sensitized sandwiched structure, wherein the upconversion core serves as light transducers to transfer energy to the neighboring photosensitizers to produce reactive oxygen species (ROS). With HBO, photodynamic process can generate abundant ROS in the intrinsically hypoxic tumor. It is revealed for the first time that HBO-assisted PDT decomposes collagen in the extracellular matrix of tumor and thus facilitates the diffusion of oxygen and penetration of UNPSs into the deeper area of tumor. Such a synergic effect eventually results in a significantly enhanced therapeutic efficacy at a low laser power density as compared with that using UNPSs alone. In view of its good biosafety, the HBO-assisted and UNPSs-mediated PDT provides new possibilities for treatment of solid tumors.

Epitaxial growth of an inert shell around the optical active lanthanide upconversion nanoparticles (UCNPs) is a general strategy to enhance their brightness. Yet, its potential as a tool in multiplexing emission tailoring has rarely been reported. Here, by developing the atomic vacancies into color selectivity actuators, we present an efficient strategy to achieve inert-shell-modulated multiplexing upconversion in 1540 nm activated UCNPs. Artificially generated fluoride atomic vacancies, owing to the decreased NaOH/NH4F dosage during shell growth, reduce the coordination number of Y–F and lattice densities in the inert shell, leading to the core–engineered shell nanoparticles with distinctive emission profiles. The multicolor tailoring is independent of shell thickness and can be readily applied to Lu3+/Gd3+-based shells. The upconversion emission can be exploited to visualize in security decoding and in vivo multiplexing bioimaging. This method of regulating atomic vacancies based on the inert-shell engineering opens new insights of upconversion modulation in core–shell lanthanide nanostructures.

Certain obligate and facultative anaerobic microbes preferentially grow within this region, [2,3] which makes them ideal platforms for delivering antitumor therapeutics. [4,5] Different from conventional nano-drug delivery systems, bacteria-based drug carriers can be designed to generate and release drugs, which avoids the need for cumbersome post-purification or delivery protection. [6] However, bacteria sometimes can grow outside their natural niches, leading to offtarget therapeutics release that may incur severe toxicities toward normal tissues. [7,8] Therefore, it is crucial to "tune" the bacteria for precise and on-demand release of the therapeutics at the tumor site so as to minimize the side effects as well as promote antitumor therapeutic efficacy.Spatial and temporal activation of inducible or repressible gene expression systems facilitate precise gene expression as required. Ideally, programming bacteria with the capability to rapidly and precisely switch between "ON" and "OFF" states at will, would sense and respond to the physiological or pathological conditions upon utilization of certain stimuli. [9] Typically, exogenous chemical inducers, such as antibiotics, were used to achieve artificial control of gene expression in live cells. [10] However, it is very difficult to remove the residual chemical inducers, which limited the precise control of gene expression at desired levels. Light, as an external inducer, possesses high spatiotemporal control ability, non-invasiveness, and minimal cytotoxicity. Therefore, light-regulated modules have attracted wide attention for controlling molecular or cellular behavior. Among them, optogenetics combines optics and genetics in technology to rapidly activate/deactivate photo-sensitive proteins, which shows great potential in the modulation of neural activities, gene transcription, and the regulation of cellular processes within organisms. [11] Most of these applied optogenetics are blue light (BL)-based control systems, including CRY2/CIB, [12] VVD, [13] EL222, [14,15] and magnet systems. [16] However, a major hurdle in these optogenetics systems stems from poor BL penetration to turbid human tissues and potential phototoxicity. It was also noted that some red/far-red light-responsive optogenetic devices, phyB/PIF1/SPA1, [17] BphP1/PpsR2 [18] and BphS, [19] have been developed to control transgene expression. However, the in Certain anaerobic microbes with the capability to colonize the tumor microenvironment tend to express the heterologous gene in a sustainable manner, which will inevitably compromise the therapeutic efficacy and induce off-tumor toxicity in vivo. To improve the therapeutic precision and controllability of bacteriabased therapeutics, Escherichia coli Nissle 1917 (EcN), engineered to sense blue light and release the encoded flagellin B (flaB), is conjugated with lanthanide upconversion nanoparticles (UCNPs) for near-infrared (NIR) nano-optogenetic cancer immunotherapy. Upon 808 nm photoirradiation, UCNPs emit at the blue region to photoactivat...