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Visual measurement is widely used in industrial manufacturing and assembly fields. Due to the fact that the refractive index field of the measurement environment is inhomogeneous, the transmitted light for visual measurements will produce errors. To compensate for these errors, we introduce a binocular camera for visual measurement based on the reconstruction of a nonuniform refractive index field using the schlieren method, followed by the reduction of the inverse ray path by the Runge–Kutta method to compensate for the measurement error introduced by the nonuniform refractive index field. Finally, the effectiveness of the method is experimentally verified, with a reduction in measurement error of about 60% in the built measurement environment.

Metal-based carbon monoxide (CO)-releasing molecules have been shown to exert anti-inflammatory and anti-oxidative properties maintaining gastric mucosal integrity. We are interested in further development of metal-free CO-based therapeutics for oral administration. Thus, we examine the protective effect of representative CO prodrug, BW-CO-111, in rat models of gastric damage induced by necrotic ethanol or aspirin, a representative non-steroidal anti-inflammatory drug. Treatment effectiveness was assessed by measuring the microscopic/macroscopic gastric damage area and gastric blood flow by laser flowmetry. Gastric mucosal mRNA and/or protein expressions of HMOX1, HMOX2, nuclear factor erythroid 2-related factor 2, COX1, COX2, iNos, Anxa1 and serum contents of TGFB1, TGFB2, IL1B, IL2, IL4, IL5, IL6, IL10, IL12, tumor necrosis factor α, interferon γ, and GM-CSF were determined. CO content in gastric mucosa was assessed by gas chromatography. Pretreatment with BW-CO-111 (0.1 mg/kg, i.g.) increased gastric mucosal content of CO and reduced gastric lesions area in both models followed by increased GBF. These protective effects of the CO prodrug were supported by changes in expressions of molecular biomarkers. However, because the pathomechanisms of gastric damage differ between topical administration of ethanol and aspirin, the possible protective and anti-inflammatory mechanisms of BW-CO-111 may be somewhat different in these models., Graphical abstract Carbon monoxide (CO) is an endogenous molecule exerting anti-inflammatory activity. BW-CO-111 is an organic CO prodrug. BW-CO-111 exerts gastroprotective effect against ethanol- and aspirin-induced damage. The specific mechanism of the beneficial activity of CO released from BW-CO-111 depends on the type of gastric tissue injury.Image 1

Hypoxia is a pathological hallmark of solid tumors. Detection of hypoxia is therefore of great interest for tumor diagnosis and treatment. As a well-established biomarker of hypoxia, nitroreductase (NTR) has been widely exploited in the development of hypoxia-responsive fluorescent probes on the basis of its enzymatic activity to reduce nitroaryl groups. However, studies on the relationship between the nitroaryl structure and the probe performance for optimal probe design are still rare. Here we report a comparative investigation of nitroaryl groups and identification of the optimal nitroaryl structure for developing new fluorescent probes with extremely high efficiency in the detection of NTR and the imaging of hypoxic tumor cells. Specifically, we synthesized a series of resorufin-based fluorescent probes containing different nitroaryl groups, compared their fluorescence responses to NTR, and identified 2-nitro-N-methyl-imidazolyl as the optimal nitroaryl group that is much more efficient than the most widely used 4-nitrophenyl for NTR detection. The structure-performance relationship was then studied by theoretical molecular docking, revealing the unique features of 2-nitro-N-methyl-imidazolyl in binding and reaction with NTR. We further incorporated the 2-nitro-N-methyl-imidazolyl group into a near-infrared (NIR) hemicyanine fluorophore and developed a NIR fluorescent probe NFP-7 for the detection of NTR and hypoxic tumor cells. NFP-7 exhibits a strong fluorescence increase toward NTR in vitro with an ultrafast (within 40 seconds to fluorescence maximum) and ultrasensitive (0.2 ng mL-1 detection limit) response. NFP-7 has also been demonstrated for imaging the degree of hypoxia in live tumor cells and, more importantly, in a murine tumor model. Our study provides important insights into hypoxia probe development and new tools for hypoxia imaging.

The family Tomoceridae is among the earliest derived collembolan lineages, thus is of key importance in understanding the evolution of Collembola. Here, we assembled a chromosome-level genome of one tomocerid species Tomocerus qinae by combining Nanopore long reads and Hi-C data. The final genome size was 334.44 Mb with the scaffold/contig N50 length of 71.85/13.94 Mb. BUSCO assessment indicated that 96.80% of complete arthropod universal single-copy orthologs (n = 1,013) were present in the assembly. The repeat elements accounted for 26.11% (87.26 Mb) and 494 noncoding RNAs were identified in the genome. A total of 20,451 protein-coding genes were predicted, which captured 96.0% (973) BUSCO genes. Gene family evolution analyses identified 4,825 expanded gene families of T. qinae, among them, 47 experienced significant expansions, and these significantly expanded gene families mainly involved in proliferation and growth. This study provides an important genomic resource for future evolution and comparative genomics analyses of Collembola.

Blood-brain barrier (BBB) disruption is a pivotal pathophysiological process in ischemic stroke. Although temporal changes in BBB permeability during the acute phase have been widely studied, little is known about the chronic phase of cerebrovascular changes that may have a large impact on the long-term outcome. Therefore, this study was aimed to measure cerebral vascular abnormalities using CT perfusion in nine rhesus monkeys subjected to transient middle cerebral artery occlusion (tMCAO) for ≥1 year (MCAO-1Y+). The level of cerebral perfusion demonstrated by mean transit time was significantly higher in the ipsilateral caudate nucleus, white matter, thalamus, hippocampus, and contralateral thalamus in MCAO-1Y+ compared with the other nine age-matched control monkeys. The increase in BBB permeability measured through the permeability surface was found in the same ten regions of interest ipsilaterally and contralaterally. We also found decreased levels of Aβ 42/40 ratio in the cerebrospinal fluid (CSF), suggesting a potential link between post-MCAO cognitive decline and Aβ metabolism. Overall, we demonstrated significant cerebral hypoperfusion, BBB disruption, and CSF Aβ decrease during the rehabilitation stage of ischemic stroke in a non-human primate model. Future studies are needed to elucidate the cause-effect relationship between cerebrovascular disruptions and long-term neurological deficits.

The typical non-axisymmetric temperature field distribution in the tail nozzle outlet area of the combustion chamber of an aircraft engine can reflect the operating state of the engine. As an effective non-contact method for measuring a non-axisymmetric temperature field, the traditional background-oriented schlieren (BOS) method has the problem that the extraction accuracy of light deflection is not high. In this paper, interference fringes are introduced into the schlieren measurement, and the highly sensitive fringe offset replaces the traditional background speckle offset for measurement, which realizes accurate reconstruction of the non-axisymmetric temperature field. Firstly, through the interferometric fringe schlieren (IFS) method comprising multiple sets of double-slit interferometric systems and imaging sensors, the offset of the interference fringe after passing through the non-axisymmetric temperature field is measured by image processing. The spatial refractive index field is then reconstructed by the filtered back-projection algorithm under the sector model proposed in this paper and the spatial temperature field is obtained. The experimental results show that the temperature field reconstruction error is smaller for the IFS method than the BOS method, the measurement area is accurate from 0.5 mm for the BOS method to 0.2 mm for the IFS method and the temperature error range is reduced from 50 K for the BOS method to 25 K for the IFS method.

As the medical community puts forward higher requirements for the speed and convenience of disease diagnosis, point-of-care testing has become a hot research topic to overcome various kinds of healthcare problems. Blood test is considered to be highly sensitive and accurate in clinical diagnosis. However, conventional plasma separation system tends to be bulky and needs professional operations. Moreover, imprecise separation may cause residual biochemical substances such as blood cells to affect the detection results. In this work, to solve these problems, we designed a portable centrifugal microfluidic platform for automatic, rapid and ultraprecise blood separation. The disc consists of multichambers and multi-microchannels where a plasma reservoir and a cell reservoir are connected to each other and collinear with the center of the circle. This structure overcomes the weakness of low separation efficiency (when hematocrit increases) under the traditional blood separation structure (bifurcation structure). As a result, the proposed system achieved 99.9% plasma purity, 99.9% separation efficiency (with a blood hematocrit of 48%) and 32.5% plasma recovery rate in the 50s, which provides a strong guarantee for rapid blood diagnosis and analysis, especially in areas where medical resources are limited.

A high-content bioorthogonal prodrug with multiple outputs using the "click, cyclize, and release" concept is described. The proof of concept is established by the co-delivery of a gasotransmitter carbon monoxide, an anticancer drug floxuridine, and an in situ generated fluorescent reporter molecule for real-time monitoring of the prodrug activation. Bioorthogonal prodrugs as such are invaluable tools for the co-delivery of other drug payloads for multimodal therapy.

Smart drugs, such as antibody-drug conjugates, for targeted therapy rely on the ability to deliver a warhead to the desired location and to achieve activation at the same site. Thus, designing a smart drug often requires proper linker chemistry for tethering the warhead with a vehicle in such a way that either allows the active drug to retain its potency while being tethered or ensures release and thus activation at the desired location. Recent years have seen much progress in the design of new linker activation strategies. Herein, we review the recent development of chemical strategies used for linking the warhead with a delivery vehicle for preferential cleavage at the desired sites.

Carbon monoxide (CO) is a known endogenous signaling molecule with potential therapeutic indications in treating inflammation, cancer, neuroprotection, and sickle cell disease among many others. One of the hurdles in using CO as a therapeutic agent is the development of pharmaceutically acceptable delivery forms for various indications. Along this line, we have developed organic CO prodrugs that allow for packing this gaseous molecule into a dosage form for the goal of "carbon monoxide in a pill." This should enable non-inhalation administration including oral and intravenous routes. These prodrugs have previously demonstrated efficacy in multiple animal models. To further understand the CO delivery efficiency of these prodrugs in relation to their efficacy, we undertook the first pharmacokinetic studies on these prodrugs. In doing so, we selected five representative prodrugs with different CO release kinetics and examined their pharmacokinetics after administration via oral, intraperitoneal, and intravenous routes. It was found that all three routes were able to elevate systemic CO level with delivery efficiency in the order of intravenous, oral, and intraperitoneal routes. CO prodrugs and their CO-released products were readily cleared from the circulation. CO prodrugs demonstrate promising pharmaceutical properties in terms of oral CO delivery and minimal drug accumulation in the body. This represents the very first study of the interplay among CO release kinetics, CO prodrug clearance, route of administration, and CO delivery efficiency.

A new species of Entomobrya Rondani: E. tristriata sp. nov., from Jilin, one province of the Northeast China and first record of Entomobryoides sotoadamesi Jordana, Potapov & Baquero, 2011, are herein described. Entomobrya tristriata sp. nov. is characterised by three longitudinal dark blue stripes from Th. II to Abd. III, prelabral smooth chaetae and larger subapical tooth on mucro. However, in most species of Entomobrya, prelabral chaetae are ciliated and subapical tooth is subequal to the apical one. Entomobryoides sotoadamesi was first described from Far East of Russia and Chinese specimens agree with the original description.

BackgroundInositol 1,4,5-trisphosphate receptors (IP3Rs) are a family of intracellular Ca2+ release channels located on the membrane of endoplasmic reticulum, which have been shown to play critical roles in various cellular and physiological functions. However, their function in regulating gastrointestinal (GI) tract motility in vivo remains unknown. Here, we investigated the physiological function of IP3R1 in the GI tract using genetically engineered mouse models.MethodsPdgfrb-Cre mice were bred with homozygous Itpr1 floxed (Itpr1f/f) mice to generate conditional IP3R1 knockout (pcR1KO) mice. Cell lineage tracing was used to determine where Pdgfrb-Cre-mediated gene deletion occurred in the GI tract. Isometric tension recording was used to measure the effects of IP3R1 deletion on muscle contraction.ResultsIn the mouse GI tract, Itpr1 gene deletion by Pdgfrb-Cre occurred in smooth muscle cells, enteric neurons, and interstitial cells of Cajal. pcR1KO mice developed impaired GI motility, with prolonged whole-gut transit time and abdominal distention. pcR1KO mice also exhibited lethality as early as 8weeks of age and 50% of pcR1KO mice were dead by 40weeks after birth. The frequency of spontaneous contractions in colonic circular muscles was dramatically decreased and the amplitude of spontaneous contractions was increased in pcR1KO mice. Deletion of IP3R1 in the GI tract also reduced the contractile response to the muscarinic agonist, carbachol, as well as to electrical field stimulation. However, KCl-induced contraction and expression of smooth muscle-specific contractile genes were not significantly altered in pcR1KO mice.ConclusionsHere, we provided a novel mouse model for impaired GI motility and demonstrated that IP3R1 plays a critical role in regulating physiological function of GI tract in vivo.

Formation and general characteristics of multi-dimensional tibetan traditional motion are discussed in a data mining perspective in this paper. In the proposed data analytic framework, the following aspects are considered. (1) Data with core characteristics do not have core characteristics of large sample data and we cannot use the existing methods to draw meaningful conclusions. (2) The multidimensional IRT observation score equivalent is obtained by converting the node value of each dimension capability in multidimensional test to the one-dimensional capability node value. (3) The decision algorithm accurately completely describes inference relationship between the condition attribute and the decision attribute in decision table. With these mentioned novelties, we conduct the analysis on the tibetan traditional motion feature analysis and the classifications. The experimental results prove that we can obtain a better performance using the proposed paradigm.

Carbon monoxide (CO) is an endogenously produced gasotransmitter in mammals, and may have signaling roles in bacteria as well. It has many recognized therapeutic effects. A significant challenge in this field is the development of pharmaceutically acceptable forms of CO delivery with controllable and tunable release rates. Herein, the structure-release rate studies of the first class of organic CO prodrugs that release CO in aqueous solution at neutral pH is described.

One major challenge in the development of CO as a therapeutic agent is its controllable delivery in a pharmaceutically acceptable form. Herein, we describe for the first time a general chemical strategy to esterase-sensitive organic CO-prodrugs.

Previously, we reported a class of MDM2-MDM4 dimerization inhibitors that upregulate p53 and showed potent anticancer activity in animal models. However, water solubility hinders their further development. Herein we describe our effort to develop a prodrug approach that overcomes the solubility problem. The prodrug of BW-AQ-238, a potent anthraquinone analog, was made by esterification of the hydroxyl group with various natural amino acids. Cytotoxicity of these compounds toward Hela and EU-1 cells, their aqueous solubility, and the release kinetics of these prodrugs in buffer and in the presence of hydrolytic enzymes were studied. The results demonstrate that the amino acid prodrug approach significantly improved the water solubility while maintaining the potency of the parent drug.

Hydrocarbon fuel reforming has been proven useful for producing hydrogen that is utilized on road vehicles, but it is associated with reaction mechanism and catalyst characterization. In this study, a reduced mechanism for n-heptane/toluene reforming over an advanced Pt/Rh TWC is adopted to investigate the effects of the reaction conditions on H2 and CO concentrations. The physical and chemical properties of the advanced catalyst are examined using SEM, XRD and XPS analyses. The contrasted experiments are conducted to study the composition variation tendency of the reforming reactor gas product. The results show that the POX reaction is most likely to occur considering the stoichiometric ratio of H2/CO, and other reactions are SR or ATR. The coke formation and carbon deposition occur on the catalyst surface, and the diffraction peaks corresponding to the metallic Pt are observed, while no obvious peaks characteristic of Rh are detected. The characteristics of the concentration trend of n-heptane/toluene reforming can represent H2 and CO yield features of diesel reforming in a way, nevertheless, the difference of the average H2 and CO concentration is remarkable.

The analysis of in-cylinder combustion temperatures using flame image processing technology is reliable. This method can accurately, intuitively, and in real time obtain the temperature field distribution law of the combustion flame in the cylinder, so we can more deeply understand the characteristics of the combustion process of internal combustion engines. In this paper, a high-speed charge-coupled device (CCD) camera is used to record an in-cylinder combustion image, which is calculated and corrected according to the principle of three primary color temperature measurement, and the temperature field distribution of the combustion flame in the diesel engine cylinder is analyzed in detail. In addition, the temperature of the typical combustion flame images under the open-cycle and closed cycle conditions is compared by the CMS2002 measurement and MATLAB program, respectively. The results show that the accuracy of the MATLAB program is acceptable in general but not entirely acceptable in a few ways.

In order to benefit from a realistic hydrogen production device equipped on a vehicle, issues with the effects of the process parameters on H2 and CO yield need to be resolved. In this study, a reduced mechanism for n-heptane (as a surrogate diesel) reforming over a Pt/CeO2-Al2O3 catalyst is adopted to investigate the effects of the process parameters on H2 and CO yield, and the preferred process parameters are concluded. In addition, the comparison of reforming bench tests of diesel fuel and n-heptane under typical diesel engine operating conditions is conducted. The n-heptane reforming simulation results show that the maximum H2 and CO yield moves toward unity with the decreased GHSV and increased reaction temperature, and the GHSV of 10,000 1/h, O2/C ratio of 0.6 and reaction temperature of 500 °C is preferable. The contrast experiments reveal that the change trend of H2 and CO yield displays consistence, although the difference of the average H2 and CO yield results is obvious. The characteristics of n-heptane reforming can represent H2 and CO yield features of diesel fuel reforming at typical reaction temperatures in a way.

A bottleneck for developing CO-based therapeutics is the lack of a safe and controllable delivery form. Herein, we describe efforts toward organic CO prodrugs with dual-responsive endogenous triggers. One representative CO prodrug showed significant anti-inflammatory effects both in vitro and in a LPS-simulated systemic inflammation model. These results firmly establish such CO prodrugs as either research tools or candidate compounds for the treatment of systemic inflammation or inflammation related organ injuries.

Prodrug approaches represent an excellent solution to certain pharmaceutical issues commonly encountered in the drug discovery and development process. Along this line, the chemistry needed for the bio-reversible derivatization of drug functional groups for on-demand release is critical. In recent years, "click and release" approaches have shown great promise in the design of prodrugs because of their bioorthogonality and controlled bond-cleavage, which help ensure prodrug stability during circulation and ready cleavage at the desired site of action. This review highlights recent developments of this research field and discusses issues yet to be addressed.

The aim of present work is to bridge the gap of knowledge concerning crystallite size, graphene layers curvature and inter-layer distance as nanostructure characteristics of soot primary particles, and also to comprehensively characterize the morphology of soot emission in a light hydrocarbon premixed charge compression ignition (PCCI) engine. In this study, the chemical composition, morphology and nano-structure of particulate emissions between conventional diesel and light hydrocarbon PCCI engine were performed with thermogravimetric analysis, gas chromatography mass spectrometry, and high-resolution transmission electron microscopy technology. The results show that the volatile matter content of light hydrocarbon is much higher than that of diesel, and thermogravimetry and differential thermogravimetry curves of light hydrocarbon shift to low temperature regions. The total organic components of particulate matter of light hydrocarbon PCCI engine are less, and the corresponding separation time is shorter. The structure of particles produced in light hydrocarbon PCCI engine is more open, and the size of aggregates is smaller. Fractal dimensions of 1.774 and 1.691 are obtained for soot particles in light hydrocarbon PCCI engine, compared to that of 1.81 and 1.785 in conventional diesel engine. Compared to conventional diesel engine, fringe separation distance and fringe tortuosity in light hydrocarbon PCCI engine are smaller while fringe length is larger. The primary particle nanostructures of light hydrocarbon PCCI engine incline to graphitize and change into the orderly structure. Compared with conventional diesel combustion, the average primary particle diameter of light hydrocarbon PCCI approximately reduces 2.0% at 75% load and 18.2% at 100% load, respectively.

Ecology and habits of the genus Paragavialidium are discussed. Paragavialidium islandium Zha and Wen sp. nov. is described and illustrated with photographs and compared with similar taxa. A taxonomic review of the genus Paragavialidium is provided and a key to total 12 species of Paragavialidium is given.

Prodrugs that release hydrogen sulfide upon esterase-mediated cleavage of an ester group followed by lactonization are described herein. By modifying the ester group and thus its susceptibility to esterase, and structural features critical to the lactonization rate, H2 S release rates can be tuned. Such prodrugs directly release hydrogen sulfide without the involvement of perthiol species, which are commonly encountered with existing H2 S donors. Additionally, such prodrugs can easily be conjugated to another non-steroidal anti-inflammatory agent, leading to easy synthesis of hybrid prodrugs. As a biological validation of the H2 S prodrugs, the anti-inflammatory effects of one such prodrug were examined by studying its ability to inhibit LPS-induced TNF-α production in RAW 264.7 cells. This type of H2 S prodrugs shows great potential as both research tools and therapeutic agents.

The present research concentrates on the fuel properties and engine operating conditions on combustion and emission characteristics especially for morphology and nano-structure of a light hydrocarbons PCCI engine. The experiments were conducted by using gas chromatography-mass spectrometry, thermogravimetric analysis and high-resolution transmission electron microscopy. Additionally, the performance, combustion and gaseous pollutant emissions characteristics were also performed. The results indicate that the carbon chain length of main compounds in light hydrocarbons sample is shorter and the volatile matter content is higher. TG/DTG curves of light hydrocarbons move to a lower temperature region compared to diesel, which is due to lower decomposition temperature and higher volatility of light hydrocarbons. The performance characteristics show that BSFC is higher and BTE is lower in light hydrocarbons PCCI engine compared to conventional diesel engine. The combustion and emission characteristics show that the in-cylinder peak pressure of light hydrocarbons PCCI engine is reduced by 18.1%, and the pressure rise rate and heat release rate present a consistent variation trend compared to conventional diesel engine. Light hydrocarbons PCCI engine exhibits higher THC emission with respect to different engine load, while CO and NOx emissions are lower. Compared with conventional diesel engine, the soot aggregate of light hydrocarbons PCCI engine exhibits more sparse, and it appears more chain-like. Additionally, the primary particles in light hydrocarbons PCCI engine represent more ordered graphitic and fullerenic nanostructure.

A study on particulate matter (PM) of a compression ignition engine under partial premixed combustion has been performed. Particularly, the microscopic analyses (SEM and TEM) of several samples at the exhaust were carried out to describe the morphology and ordering degree of particles produced by the combustion of diesel and 15% diesel blended with 85% light hydrocarbon (named DLH). Characterization parameters such as fractal dimension, fringe separation distance, fringe length and fringe tortuosity were analyzed to further study the particle structure. Besides, the particle size distributions at medium and high load were compared. The results demonstrated that the particle size distribution presents as quasi-monodisperse and the average diameter of DLH is smaller than that of diesel. The diesel particles move to a larger size range at higher load, while DLH particles show an obvious shift to smaller particles at higher load, which is related to the competition between surface growth and oxidation rates.

BACKGROUND: Inositol 1,4,5-trisphosphate receptors (IP(3)Rs) are a family of intracellular Ca(2+) release channels located on the membrane of endoplasmic reticulum, which have been shown to play critical roles in various cellular and physiological functions. However, their function in regulating gastrointestinal (GI) tract motility in vivo remains unknown. Here, we investigated the physiological function of IP(3)R1 in the GI tract using genetically engineered mouse models. METHODS: Pdgfrb-Cre mice were bred with homozygous Itpr1 floxed (Itpr1(f/f)) mice to generate conditional IP(3)R1 knockout (pcR1KO) mice. Cell lineage tracing was used to determine where Pdgfrb-Cre-mediated gene deletion occurred in the GI tract. Isometric tension recording was used to measure the effects of IP(3)R1 deletion on muscle contraction. RESULTS: In the mouse GI tract, Itpr1 gene deletion by Pdgfrb-Cre occurred in smooth muscle cells, enteric neurons, and interstitial cells of Cajal. pcR1KO mice developed impaired GI motility, with prolonged whole-gut transit time and abdominal distention. pcR1KO mice also exhibited lethality as early as 8 weeks of age and 50% of pcR1KO mice were dead by 40 weeks after birth. The frequency of spontaneous contractions in colonic circular muscles was dramatically decreased and the amplitude of spontaneous contractions was increased in pcR1KO mice. Deletion of IP(3)R1 in the GI tract also reduced the contractile response to the muscarinic agonist, carbachol, as well as to electrical field stimulation. However, KCl-induced contraction and expression of smooth muscle-specific contractile genes were not significantly altered in pcR1KO mice. CONCLUSIONS: Here, we provided a novel mouse model for impaired GI motility and demonstrated that IP(3)R1 plays a critical role in regulating physiological function of GI tract in vivo.

Controlled activation is a critical component in prodrug development. Herein we report a concentration-sensitive platform approach for bioorthogonal prodrug activation by taking advantage of reaction kinetics. Using two “click and release” systems, we demonstrate enrichment and prodrug activation specifically in mitochondria to demonstrate the principle of this approach. In both cases, the payload (doxorubicin or carbon monoxide) was released inside the mitochondrial matrix upon the enrichment-initiated click reaction. Furthermore, mitochondria-targeted delivery yielded substantial augmentation of functional biological and therapeutic effects in vitro and in vivo, as compared to controls that did not result in enrichment. This method is thus a platform for targeted drug delivery amenable to conjugation with a variety of molecules and not limited to cell-surface delivery. Taken together, these two click and release pairs clearly demonstrate the concept of enrichment-triggered drug release and critical feasibility of treating clinically relevant diseases such as acute liver injury and cancer., Graphical Abstract

A chemical strategy was developed wherein a single trigger sets in motion a three-reaction cascade leading to the release of more than one drug-component in sequence with the generation of a fluorescent side product for easy monitoring. As a proof of concept, codelivery of CO with the antibiotic metronidazole was demonstrated.