An artificial intelligence handheld sensor for direct reading of nickel ion and ethylenediaminetetraacetic acid in food samples using ratiometric fluorescence cellulose paper microfluidic chip.

User-friendly in-field sensing protocol is crucial for the effective tracing of intended analytes under less-developed countries or resources-limited environments. Nevertheless, existing sensing strategies require professional technicians and expensive laboratory-based instrumentations, which are not capable for point-of-care on-site analyses. To address this issue, artificial intelligence handheld sensor has been designed for direct reading of Ni2+ and EDTA in food samples. The sensing platform incorporates smartphone with machine learning-driven application, 3D-printed handheld device, and cellulose paper microfluidic chip stained with ratiometric red-green-emission carbon dots (CDs). Intriguingly, Ni2+ introduction makes green fluorescent (FL) of CDs glow but red FL fade because of the coordination of Ni2+ with CDs verified by density functional theory (DFT), concurrently manifesting continuous FL colour transition from red to green. Subsequent addition of EDTA renders FL of CDs-Ni2+ recover owing to the capture of Ni2+ from CDs by EDTA based on strong chelation effect of EDTA on Ni2+ confirmed via DFT, accompanying with a noticeable colour returning from green to red. Inspired by above FL phenomena, CDs-based cellulose paper microfluidic chips are first fabricated to facilitate point-of-care testing of Ni2+ and EDTA. Designed fully-automatic handheld sensor is utilized to directly output Ni2+ and EDTA concentration in water, milk, spinach, bread, and shampoo based on wide linear ranges of 0-48 µM and 0-96 µM, and low limits of detection of 0.274 µM and 0.624 µM, respectively. The proposed protocol allows for speedy straightforward on-site determination of target analytes, which will trigger the development of automated and intelligent sensors in near future.

Tuning molecular assembly behavior to amplify the sonodynamic activity of porphyrins for efficient antibacterial therapy.

Sonodynamic therapy (SDT) is a promising strategy to treat deep-seated bacterial infections with good tissue penetration and spatiotemporal controllability. However, the low ROS generation efficiency of current sonosensitizers limits the development of SDT. Herein, we report a porphyrin derivative, TAPyPP-2, the sonodynamic activity of which is enhanced with less oxygen dependence by tuning its molecular assembly behavior. TAPyPP-2 can spontaneously form an ultra-small nano-assembly with a diameter of 6 nm in water by conjugation with primary amine salt-decorated pyridinium via π-π staking. The ultra-small assembly behavior can lower the energy gap between singlet and triplet states to 0.01 eV and promote the separation of holes and electrons, which facilitates ROS generation under ultrasound irradiation, in particular type I ROS. The unique hydrophilic ratio and positive charges endow TAPyPP-2 with superior abilities to interact with Staphylococcus aureus, resulting in extremely high sonodynamic antibacterial activity. Therefore, TAPyPP-2 successfully kills Staphylococcus aureus bacteria in the enclosed cavity of synovial joint and achieves effective SDT of septic arthritis. This work is anticipated to motivate enormous interest in the development of efficient SDT.

A New Surgical Assistance Aid for Mesiodens Extraction Based on the Ideal Approach.

BACKGROUND: To date, the classification of mesiodens has been based on the location, crown orientation, and morphology; however, there is no assistance aid focusing on choosing surgical approach. PURPOSE: This study aimed to introduce and evaluate a new surgical assistance aid for mesiodens extraction based on surgical approach. STUDY DESIGN, SETTING, SAMPLE: For the retrospective trial part of this study, case data from mesiodens patients who had surgery at the Affiliated Stomatological Hospital was collected, and a new surgical assistance aid was developed. A prospective randomized controlled trial was conducted on mesiodens patients who were seen in our department (patients with one mesiodens were included). PREDICTOR VARIABLE: The predictor variable was surgical approach either with or without the surgical assistance aid. Subjects were randomized to one of the two study groups. For subjects assigned to the group using the surgical assistance guide, the approach was selected according to the aid detailed in this study. For subjects assigned to the group without the surgical assistant aid, 2 residents chose an approach based on their judgment and review of relevant imaging and physical examination. MAIN OUTCOME VARIABLES: The preoperative evaluation time, operative time, and complications associated with surgery were recorded separately for the two groups. COVARIATES: The age and sex were also recorded. ANALYSES: Variables were analyzed using the independent t-test and χ2 test. The level of statistical significance is P < .05. RESULTS: In the retrospective trial part, a new surgical assistance aid for mesiodens extraction was developed based on the ideal surgical approach. In the prospective randomized controlled trial, the experimental group (n = 50) was statistically significant in preoperative evaluation time (4.51 ± 0.34 mins vs 5.43 ± 0.34 mins) and operative time (31.87 ± 5.57 mins vs 36.32 ± 5.28 mins) compared to the control group (n = 50) (P < .001). There was no significant intergroup difference in complications associated with surgery (P > .05). CONCLUSION AND RELEVANCE: The new surgical assistance aid developed in this study guides surgeons to ease the selection of surgical approaches and shorten the operative time.

Design and Performance Verification of a Novel RCM Mechanism for a Minimally Invasive Surgical Robot.

Minimally invasive surgical robots have the advantages of high positioning accuracy, good stability, and flexible operation, which can effectively improve the quality of surgery and reduce the difficulty for doctors to operate. However, in order to realize the translation of the existing RCM mechanism, it is often necessary to add a mobile unit, which is often bulky and occupies most space above the patient's body, thus causing interference to the operation. In this paper, a new type of planar RCM mechanism is proposed. Based on this mechanism, a 3-DOF robotic arm is designed, which can complete the required motion for surgery without adding a mobile unit. In this paper, the geometric model of the mechanism is first introduced, and the RCM point of the mechanism is proven during the motion process. Then, based on the establishment of the geometric model of the mechanism, a kinematics analysis of the mechanism is carried out. The singularity, the Jacobian matrix, and the kinematic performance of the mechanism are analyzed, and the working space of the mechanism is verified according to the kinematic equations. Finally, a prototype of the RCM mechanism was built, and its functionality was tested using a master-slave control strategy.

How Does Molecular Diameter Correlate with the Penetration Barrier of Small Gas Molecules on Porous Carbon-Based Monolayer Membranes?

Molecular diameter is an essential molecule-size descriptor that is widely used to understand, e.g., the gas separation preference of a permeable membrane. In this contribution, we have proposed two new molecular diameters calculated respectively by the circumscribed-cylinder method (Dn') and the group-separated method (Dn), and compared them with the already known kinetic diameter (Dk), averaged diameters (Dpa), and maximum diameters (Dpm and Dmm) in correlating with the penetration barriers of small gas molecules on a total of 14 porous carbon-based monolayer membranes (PCMMs). D1' and D2' give the best barrier-diameter correlations with average Pearson's correlation coefficients of 0.91 and 0.90, which are markedly larger than those (0.77, 0.76, 0.60, 0.48, 0.33, and 0.32) for D1, D2, Dk, Dpa, Dpm, and Dmm. Our results manifest that the choice of vdW radii set does not drastically change the barrier-diameter correlation. Our newly defined D1', D2', D1, and D2, especially D1' and D2', show universal applicability in predicting the relative permeability of small gas molecules on different PCMMs. The circumscribed-cylinder method proposed here is a facile approach that considers the molecule's directionality and can be applicable to larger molecules. The excellent linear correlation between Dn' and gas penetration barrier implies that the computationally less demanding molecular diameter Dn' can be an alternative to the penetration barrier in diagnosing the gas separation preference of the PCMMs.

New Insights into the Structural and Binding Properties on Aß Mature Fibrils Due to Histidine Protonation Behaviors.

Histidine tautomeric behaviors have been considered origin factors for controlling the structure and aggregation properties of misfolding peptides. Except for tautomeric behaviors, histidine protonation behaviors definitely have the same capacities due to the net charge changes and the various N/N-H orientations on imidazole rings. However, such phenomena are still unknown. In the current study, Aß mature fibrils substituted with various protonation states were performed by molecular dynamics simulations to investigate the structure and binding properties. Our results show that all kinds of protonation states can increase the ΔG1 stability and decrease ΔG2 and ΔG3 stabilities. A significantly higher averaged ß-sheet content was detected in (εεp), (εpp), and (ppp) fibrils in one, two, and three protonation stages, respectively. Impressively, we found that the substituted fibril with specific protonated states can control the N-terminus structural properties. Further analysis confirmed that H6 and H13 are more important than H14 since the H-bond donor and receptor cooperate among C1/C3/C8_H6, C1/C3/C8_H13, and C1/C3/C8_E11. Furthermore, the mechanism of protonation behaviors was discussed. The current study is helpful for understanding the histidine protonation behaviors on one, two, and three protonation stages, which provides new horizons for exploring the origin of protein folding and misfolding.

Control of aflatoxin M1 in skim milk by high voltage atmospheric cold plasma.

Cold plasma has potential for the degradation of aflatoxins in corn and hazelnuts; however, this has not been demonstrated for aflatoxin in milk. In this study, the efficacy of high voltage atmospheric cold plasma (HVACP) on the reduction of aflatoxin M1 (AFM1) in skim milk improved with increasing treatment times (1-20 min), using gas containing 65% oxygen (MA65) rather than air, increasing voltage (60-80 kV) and reducing sample volume (30 mL-10 mL). Direct treatment was more effective than indirect treatment. AFM1 in milk was degraded by 65.0 % and 78.9 % by air and MA65 respectively in 20 min with no change in milk colour. The toxicity of AFM1 after treatment was assessed using a brine shrimp model. A five-minute HVACP treatment reduced the toxicity of AFM1 by 83.9 % based on the increase in brine shrimp survival. HVACP is a promising method to reduce AFM1 in milk.

Effects of Radio Frequency Tempering on the Temperature Distribution and Physiochemical Properties of Salmon (Salmo salar).

Salmon (Salmo salar) is a precious fish with high nutritional value, which is perishable when subjected to improper tempering processes before consumption. In traditional air and water tempering, the medium temperature of 10 °C is commonly used to guarantee a reasonable tempering time and product quality. Radio frequency tempering (RT) is a dielectric heating method, which has the advantage of uniform heating to ensure meat quality. The effects of radio frequency tempering (RT, 40.68 MHz, 400 W), water tempering (WT + 10 °C, 10 ± 0.5 °C), and air tempering (AT + 10 °C, 10 ± 1 °C) on the physiochemical properties of salmon fillets were investigated in this study. The quality of salmon fillets was evaluated in terms of drip loss, cooking loss, color, water migration and texture properties. Results showed that all tempering methods affected salmon fillet quality. The tempering times of WT + 10 °C and AT + 10 °C were 3.0 and 12.8 times longer than that of RT, respectively. AT + 10 °C produced the most uniform temperature distribution, followed by WT + 10 °C and RT. The amount of immobile water shifting to free water after WT + 10 °C was higher than that of RT and AT + 10 °C, which was in consistent with the drip and cooking loss. The spaces between the intercellular fibers increased significantly after WT + 10 °C compared to those of RT and AT + 10 °C. The results demonstrated that RT was an alternative novel salmon tempering method, which was fast and relatively uniform with a high quality retention rate. It could be applied to frozen salmon fillets after receiving from overseas catches, which need temperature elevation for further cutting or consumption.

Nickel sulfide nanorods decorated on graphene as advanced hydrogen evolution electrocatalysts in acidic and alkaline media.

Nowadays, the fabrication of robust and earth-abundant hydrogen evolution electrocatalysts with noble-metal-like catalytic activities is still facing great challenges. In this report, nanorod (NR)-shaped nickel sulfide (NiS) is successfully decorated on graphene (Gr) by utilizing carbon cloth (CC) as a substrate (NiS-Gr-CC). Benefiting from the NR morphology and strong interfacial synergetic effect between NiS and Gr, the NiS-Gr-CC electrocatalyst shows good catalytic activity for hydrogen evolution reaction (HER). Specifically, the low Tafel slopes of 46 and 56 mV dec-1 along with the small overpotentials of 66 and 71 mV at 10 mA cm-2 are obtained in the acidic and alkaline electrolytes, respectively. Density functional theory results indicate that the combination of NiS and Gr can optimize the adsorption energy of H* during the HER process. The long-term durability measurement result reveals that our NiS-Gr-CC heterostructure has good electrocatalytic cycling stability (∼80 h) in both acidic and alkaline electrolytes. These results confirm that the NiS-Gr-CC heterostructure is a promising candidate for hydrogen evolution electrocatalyst with high catalytic activity.

Realization of Force Detection and Feedback Control for Slave Manipulator of Master/Slave Surgical Robot.

Robot-assisted minimally invasive surgery (MIS) has received increasing attention, both in the academic field and clinical operation. Master/slave control is the most widely adopted manipulation mode for surgical robots. Thus, sensing the force of the surgical instruments located at the end of the slave manipulator through the main manipulator is critical to the operation. This study mainly addressed the force detection of the surgical instrument and force feedback control of the serial surgical robotic arm. A measurement device was developed to record the tool end force from the slave manipulator. An elastic element with an orthogonal beam structure was designed to sense the strain induced by force interactions. The relationship between the acting force and the output voltage was obtained through experiment, and the three-dimensional force output was decomposed using an extreme learning machine algorithm while considering the nonlinearity. The control of the force from the slave manipulator end was achieved. An impedance control strategy was adopted to restrict the force interaction amplitude. Modeling, simulation, and experimental verification were completed on the serial robotic manipulator platform along with virtual control in the MATLAB/Simulink software environment. The experimental results show that the measured force from the slave manipulator can provide feedback for impedance control with a delay of 0.15 s.

Transformable Helical Self-Assembly for Cancerous Golgi Apparatus Disruption.

Golgi apparatus is a major subcellular organelle responsible for drug resistance. Golgi apparatus-targeted nanomechanical disruption provides an attractive approach for killing cancer cells by multimodal mechanism and avoiding drug resistance. Inspired by the poisonous twisted fibrils in Alzheimer's brain tissue and enhanced rigidity of helical structure in nature, we designed transformable peptide C6RVRRF4KY that can self-assemble into nontoxic nanoparticles in aqueous medium but transformed into left-handed helical fibrils (L-HFs) after targeting and furin cleavage in the Golgi apparatus of cancer cells. The L-HFs can mechanically disrupt the Golgi apparatus membrane, resulting in inhibition of cytokine secretion, collapse of the cellular structure, and eventually death of cancer cells. Repeated stimulation of the cancers by the precursors causes no acquired drug resistance, showing that mechanical disruption of subcellular organelle is an excellent strategy for cancer therapy without drug resistance. This nanomechanical disruption concept should also be applicable to multidrug-resistant bacteria and viruses.

[Reactivation of Passivated Biochar/Nanoscale Zero-Valent Iron by an Electroactive Microorganism for Cooperative Hexavalent Chromium Removal and Mechanisms].

Nanoscale zero-valent iron (nZVI) shows excellent reduction of Cr(Ⅵ), but the passivation on its outer surface can restrict its longevity and performance. To tackle this problem, this work introduced Shewanella oneidensis MR-1, a dissimilatory iron-reducing bacterium, into the chemical reduction system of aged nZVI/biochar (B) and Cr(Ⅵ). The potential synergistic effect of Cr(Ⅵ) reduction of aged nZVI/B and MR-1 was systematically investigated under varying conditions. The results indicated that aged nZVI/B and MR-1 exhibited a synergistic effect at a pH of 7, and the removal rate of Cr(Ⅵ) increased by 51.3%. Further research showed that the synergistic effect could be attenuated with the increase in the initial Cr(Ⅵ) concentration and enhanced with the increase in the MR-1 concentration. The XPS spectra confirmed that Cr(Ⅵ) was mainly removed through reduction. The dissimilatory iron-reducing ability of MR-1 played a key role in enhancing the Cr(Ⅵ) reduction. The reductive dissolution of the oxidation layers not only released reactive sites inside the nZVI, but also reduced Cr(Ⅵ) by producing ferrous ions. Moreover, B promoted the reduction by dispersing the nZVI and mediating the extracellular electron transfer. This study provides a new insight into solving the passivation problem of the long-term application of nZVI for Cr(Ⅵ) removal, which is considered a promising solution for synergistically improving the performance of nZVI in environmental remediation.

The Advances of the Structure and Function of Indoleamine 2, 3- dioxygenase 1 and Its Inhibitors.

Indoleamine 2, 3-dioxygenase 1 (IDO1) is the only rate-limiting enzyme outside the liver that catalyzes the oxidation and cracking of indole rings in the tryptophan along the kynurenine pathway (KP). The overactivation of IDO1 is closely related to the pathogenesis of various human immune and neurological diseases. As an important target for the treatment of many human serious diseases, including malignant tumors, the development of IDO1 inhibitors is of great practical significance. In this work, the structure and function of IDO1 both are summarized from the aspects of the signal pathway, catalytic mechanism, structural biology, and so on. Moreover, the current development status of IDO1 inhibitors is also systematically reviewed, which provides assistance for anti-cancer drug design based on the structure of receptors.

Effects of Boric Acid Ester Modified Magnesium Borate Whisker on the Mechanical Properties and Crystallization Kinetics of Polypropylene Composites.

Polypropylene (PP) is notch sensitive and brittle under severe conditions of deformation, limiting wider range of its usage as a structural load-bearing polymer. Hence, in this work the magnesium borate whisker (MBw), with similar mechanical properties to carbon fiber but much less expensive than polycrystalline silicon carbide, was modified by boric acid ester (BAE) and then used to fabricate PP composites. The mechanical properties, morphology, and non-isothermal crystallization property of virgin PP, PP/MBw, and PP/BAE-MBw composites were studied through mechanical testing, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC), respectively. The non-isothermal crystallization data was analyzed via Mo, Kissinger, and Dobreva methods. The results reveal that the incorporation of BAE-MBw into PP matrix results in higher tensile strength and impact strength than those of virgin PP and PP/MBw composite. The activation energies based on Kissinger were 190.20 kJ/mol for virgin PP, 206.59 kJ/mol for PP/MBw, and 218.98 kJ/mol for PP/BAE-MBw. The nucleation activities of whiskers determined by the Dobreva model were 0.86 for PP/MBw and 0.75 for PP/BAE-MBw. As a result, the whiskers, especially the modified whiskers, act as active substrates to facilitate heterogeneous nucleation, which leads to an increase in crystallization rate.

Aromatic secondary amine-functionalized fluorescent NO probes: improved detection sensitivity for NO and potential applications in cancer immunotherapy studies.

Tumor-associated macrophages (TAMs), constituting up to 50% of the solid tumor mass and commonly having a pro-tumoral M2 phenotype, are closely associated with decreased survival in patients. Based on the highly dynamic properties of macrophages, in recent years the repolarization of TAMs from pro-tumoral M2 phenotype to anti-tumoral M1 phenotype by various strategies has emerged as a promising cancer immunotherapy approach for improving cancer therapy. Herein, we present an aromatic secondary amine-functionalized Bodipy dye 1 and its mitochondria-targetable derivative Mito1 as fluorescent NO probes for discriminating M1 macrophages from M2 macrophages in terms of their difference in inducible NO synthase (iNOS) levels. The two probes possess the unique ability to simultaneously respond to two secondary oxides of NO, i.e., N2O3 and ONOO-, thus being more sensitive and reliable for reflecting intracellular NO than most of the existing fluorescent NO probes that usually respond to N2O3 only. With 1 as a representative, the discrimination between M1 and M2 macrophages, evaluation of the repolarization of TAMs from pro-tumoral M2 phenotype to anti-tumoral M1 phenotype, and visualization of NO communication during the immune-mediated phagocytosis of cancer cells by M1 macrophages have been realized. These results indicate that our probes should hold great potential for imaging applications in cancer immunotherapy studies and relevant anti-cancer drug screening.

Alterations of fecal bacterial communities in patients with lung cancer.

Emerging evidence suggests the microbiome may affect a number of diseases, including lung cancer. However, the direct relationship between gut bacteria and lung cancer remains uncharacterized. In this study, we directly sequenced the hypervariable V1-V2 regions of the 16S rRNA gene in fecal samples from patients with lung cancer and healthy volunteers. Unweighted principal coordinate analysis (PCoA) revealed a clear difference in the bacterial community membership between the lung cancer group and the healthy control group. The lung cancer group had remarkably higher levels of Bacteroidetes, Fusobacteria, Cyanobacteria, Spirochaetes, and Lentisphaerae but dramatically lower levels of Firmicutes and Verrucomicrobia than the healthy control group (P < 0.05). Despite significant interindividual variation, eight predominant genera were significantly different between the two groups. The lung cancer group had higher levels of Bacteroides, Veillonella, and Fusobacterium but lower levels of Escherichia-Shigella, Kluyvera, Fecalibacterium, Enterobacter, and Dialister than the healthy control group (P < 0.05). Most notably, correlations between certain specific bacteria and serum inflammatory biomarkers were identified. Our findings demonstrated an altered bacterial community in patients with lung cancer, providing a significant step in understanding the relationship between gut bacteria and lung cancer. To our knowledge, this is the first study to evaluate the correlations between certain specific bacteria and inflammatory indicators. To better understand this relationship, further studies should investigate the underlying mechanisms of gut bacteria in lung cancer animal models.

Hippocampal nuclear factor kappa B accounts for stress-induced anxiety behaviors via enhancing neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS-Dexras1 coupling.

Anxiety disorders are associated with a high social burden worldwide. Recently, increasing evidence suggests that nuclear factor kappa B (NF-κB) has significant implications for psychiatric diseases, including anxiety and depressive disorders. However, the molecular mechanisms underlying the role of NF-κB in stress-induced anxiety behaviors are poorly understood. In this study, we show that chronic mild stress (CMS) and glucocorticoids dramatically increased the expression of NF-κB subunits p50 and p65, phosphorylation and acetylation of p65, and the level of nuclear p65 in vivo and in vitro, implicating activation of NF-κB signaling in chronic stress-induced pathological processes. Using the novelty-suppressed feeding (NSF) and elevated-plus maze (EPM) tests, we found that treatment with pyrrolidine dithiocarbamate (PDTC; intra-hippocampal infusion), an inhibitor of NF-κB, rescued the CMS- or glucocorticoid-induced anxiogenic behaviors in mice. Microinjection of PDTC into the hippocampus reversed CMS-induced up-regulation of neuronal nitric oxide synthase (nNOS), carboxy-terminal PDZ ligand of nNOS (CAPON), and dexamethasone-induced ras protein 1 (Dexras1) and dendritic spine loss of dentate gyrus (DG) granule cells. Moreover, over-expression of CAPON by infusing LV-CAPON-L-GFP into the hippocampus induced nNOS-Dexras1 interaction and anxiety-like behaviors, and inhibition of NF-κB by PDTC reduced the LV-CAPON-L-GFP-induced increases in nNOS-Dexras1 complex and anxiogenic-like effects in mice. These findings indicate that hippocampal NF-κB mediates anxiogenic behaviors, probably via regulating the association of nNOS-CAPON-Dexras1, and uncover a novel approach to the treatment of anxiety disorders.

microRNA-608 inhibits human hepatocellular carcinoma cell proliferation via targeting the BET family protein BRD4.

Over-expression of the bromodomain and extraterminal (BET) family protein BRD4 is associated with hepatocellular carcinoma (HCC) progression. In the present study, we indentified a novel putative anti-BRD4 microRNA: microRNA-608 ("miR-608"). In HepG2 cells and primary human HCC cells, over-expression of miR-608, using a lentiviral construct, induced BRD4 downregulation and proliferation inhibition. Conversely, transfection of the miR-608 inhibitor increased BRD4 expression to promote HepG2 cell proliferation. Our results suggest that BRD4 is the primary target gene of miR-608 in HepG2 cells. shRNA-mediated knockdown or CRSIPR/Cas9-mediated knockout of BRD4 mimicked and overtook miR-608's actions in HepG2 cells. Furthermore, introduction of a 3'-untranslated region (3'-UTR) mutant BRD4 (UTR-A1718G) blocked miR-608-induced c-Myc downregulation and proliferation inhibition in HepG2 cells. In vivo, HepG2 xenograft tumor growth was significantly inhibited after expressing miR-608 or BRD4 CRSIPR/Cas9-KO construct. Importantly, BRD4 mRNA was upregulated in human HCC tissues, which was correlated with downregulation of miR-608. Together, we conclude that miR-608 inhibits HCC cell proliferation possibly via targeting BET family protein BRD4.

Development of a theranostic prodrug for colon cancer therapy by combining ligand-targeted delivery and enzyme-stimulated activation.

The high incidence of colorectal cancer worldwide is currently a major health concern. Although conventional chemotherapy and surgery are effective to some extent, there is always a risk of relapse due to associated side effects, including post-surgical complications and non-discrimination between cancer and normal cells. In this study, we developed a small molecule-based theranostic system, Gal-Dox, which is preferentially taken up by colon cancer cells through receptor-mediated endocytosis. After cancer-specific activation, the active drug Dox (doxorubicin) is released with a fluorescence turn-on response, allowing both drug localization and site of action to be monitored. The therapeutic potency of Gal-Dox was also evaluated, both in vivo and ex vivo, thus illustrating the potential of Gal-Dox as a colorectal cancer theranostic with great specificity.

PLK1-Targeted Fluorescent Tumor Imaging with High Signal-to-Background Ratio.

As significantly expressed during cell division, polo-like kinase 1 (PLK1) plays crucial roles in numerous mitotic events and has attracted interest as a potential therapeutic marker in oncological drug discovery. We prepared two small molecular fluorescent probes, 1 and 2, conjugated to SBE13 (a type II PLK1 inhibitor) to investigate the PLK1-targeted imaging of cancer cells and tumors. Enzymatic docking studies, molecular dynamics simulations, and in vitro and in vivo imaging experiments all supported the selective targeting and visualization of PLK1 expressing cells by probes 1 and 2, and probe 2 was successfully demonstrated to image PLK1-upregulated tumors with remarkable signal-to-background ratios. These findings represent the first example of small-molecule based fluorescent imaging of tumors using PLK1 as a target, which could provide new avenues for tumor diagnosis and precision therapeutics.