Harnessing External Irradiation for Precise Activation of Metal-Based Agents in Cancer Therapy.

Cancer is a significant global health issue. Platinum-based chemotherapy drugs, including cisplatin, are crucial in clinical anti-cancer treatment. However, these drugs have limitations such as drug resistance, non-specific distribution, and irreversible toxic and side effects. In recent years, the development of metal-based agents has led to the discovery of other anti-cancer effects beyond chemotherapy. Precise spatiotemporal controlled external irradiation can activate metal-based agents at specific sites and play a different role from traditional chemotherapy. These strategies can not only enhance the anti-cancer efficiency, but also show fewer side effects and non-cross-drug resistance, which are ideal approaches to solve the problems caused by traditional platinum-based chemotherapy drugs. In this review, we focus on various metal-based agent-mediated cancer therapies that are activated by three types of external irradiation: near-infrared (NIR) light, ultrasound (US), and X-ray, and give some prospects. We hope that this review will promote the generation of new kinds of metal-based anti-cancer agents.

Auditory Effects of Acoustic Noise From 3-T Brain MRI in Neonates With Hearing Protection.

BACKGROUND: Neonates with immature auditory function (eg, weak/absent middle ear muscle reflex) could conceivably be vulnerable to noise-induced hearing loss; however, it is unclear if neonates show evidence of hearing loss following MRI acoustic noise exposure. PURPOSE: To explore the auditory effects of MRI acoustic noise in neonates. STUDY TYPE: Prospective. SUBJECTS: Two independent cohorts of neonates (N = 19 and N = 18; mean gestational-age, 38.75 ± 2.18 and 39.01 ± 1.83 weeks). FIELD STRENGTH/SEQUENCE: T1-weighted three-dimensional gradient-echo sequence, T2-weighted fast spin-echo sequence, single-shot echo-planar imaging-based diffusion-tensor imaging, single-shot echo-planar imaging-based diffusion-kurtosis imaging and T2-weighted fluid-attenuated inversion recovery sequence at 3.0 T. ASSESSMENT: All neonates wore ear protection during scan protocols lasted ~40 minutes. Equivalent sound pressure levels (SPLs) were measured for both cohorts. In cohort1, left- and right-ear auditory brainstem response (ABR) was measured before (baseline) and after (follow-up) MRI, included assessment of ABR threshold, wave I, III and V latencies and interpeak interval to determine the functional status of auditory nerve and brainstem. In cohort2, baseline and follow-up left- and right-ear distortion product otoacoustic emission (DPOAE) amplitudes were assessed at 1.2 to 7.0 kHz to determine cochlear function. STATISTICAL TEST: Wilcoxon signed-rank or paired t-tests with Bonferroni's correction were used to compare the differences between baseline and follow-up ABR and DPOAE measures. RESULTS: Equivalent SPLs ranged from 103.5 to 113.6 dBA. No significant differences between baseline and follow-up were detected in left- or right-ear ABR measures (P > 0.999, Bonferroni corrected) in cohort1, or in DPOAE levels at 1.2 to 7.0 kHz in cohort2 (all P > 0.999 Bonferroni corrected except for left-ear levels at 3.5 and 7.0 kHz with corrected P = 0.138 and P = 0.533). DATA CONCLUSION: A single 40-minute 3-T MRI with equivalent SPLs of 103.5-113.6 dBA did not result in significant transient disruption of auditory function, as measured by ABR and DPOAE, in neonates with adequate hearing protection. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 5.

A recyclable Eu3+-functionalized dual-emissive metal-organic framework for portable, rapid detection and efficient removal of malachite green.

A europium-functionalized, dual-emissive, metal-organic framework-based fluorescence sensor (EuUCNDA) was constructed via post-synthetic modification of an UiO-66-type precursor through coordination interactions. EuUCNDA exhibited extremely high selectivity and sensitivity for malachite green (MG) with a low detection limit of 13.01 nM, a wide linear concentration range (0.05-50 µM), excellent anti-interference properties, a rapid response (<1 min), and the possibility of recycling. The good sensing performance of EuUCNDA enables the practical detection of MG in fish pond water and grass carp with good recoveries. Moreover, EuUCNDA can be reused for sensing MG and over 90% of fluorescence intensity can be restored after 7 cycles. Furthermore, EuUCNDA-embedded paper-based sensors combined with smartphone imaging afford portable and visual monitoring of MG in real samples. Notably, besides good sensing performance, EuUCNDA could efficiently remove MG from water. Hence, this work provides a recyclable and sensitive fluorescence sensor for portable, visual, rapid detection and efficient removal of MG.

The association between PM2.5 components and blood pressure changes in late pregnancy: A combined analysis of traditional and machine learning models.

BACKGROUND: PM2.5 is a harmful mixture of various chemical components that pose a challenge in determining their individual and combined health effects due to multicollinearity issues with traditional linear regression models. This study aimed to develop an analytical methodology combining traditional and novel machine learning models to evaluate PM2.5's combined effects on blood pressure (BP) and identify the most toxic components. METHODS: We measured late-pregnancy BP of 1138 women from the Heshan cohort while simultaneously analyzing 31 PM2.5 components. We utilized multiple linear regression modeling to establish the relationship between PM2.5 components and late-pregnancy BP and applied Random Forest (RF) and generalized Weighted Quantile Sum (gWQS) regression to identify the most toxic components contributing to elevated BP and to quantitatively evaluate the cumulative effect of the PM2.5 component mixtures. RESULTS: The results revealed that 16 PM2.5 components, such as EC, OC, Ti, Fe, Mn, Cu, Cd, Mg, K, Pb, Se, Na+, K+, Cl-, NO3-, and F-, contributed to elevated systolic blood pressure (SBP), while 26 components, including two carbon components (EC, OC), fourteen metallics (Ti, Fe, Mn, Cr, Mo, Co, Cu, Zn, Cd, Na, Mg, Al, K, Pb), one metalloid (Se), and nine water-soluble ions (Na+, K+, Mg2+, Ca2+, NH4+, Cl-, NO3-, SO42-, F-), contributed to elevated diastolic blood pressure (DBP). Mn and Cr were the most toxic components for elevated SBP and DBP, respectively, as analyzed by RF and gWQS models and verified against each other. Exposure to PM2.5 component mixtures increased SBP by 1.04 mmHg (95% CI: 0.33-1.76) and DBP by 1.13 mmHg (95% CI: 0.47-1.78). CONCLUSIONS: Our study highlights the effectiveness of combining traditional and novel models as an analytical strategy to quantify the health effects of PM2.5 constituent mixtures.

Advanced theory of mind and children's prosocial lie-telling in middle childhood: A training study.

Children's advanced theory of mind (AToM) is concurrently associated with their prosocial lie-telling. However, the causal link between AToM and prosocial lie-telling has not yet been demonstrated. To address this gap, the current study adopted a training paradigm and investigated the role of AToM in children's prosocial lie-telling in middle childhood. A total of 66 9- and 10-year-old children who did not demonstrate any prosocial lie-telling in a disappointment gift paradigm at the baseline were recruited and randomly assigned to either the experimental group (n = 32) or an active control group (n = 34). The experimental group underwent a conversation-based training program of four sessions. The results showed significantly greater gains in AToM at the posttest for the experimental group children compared with the control group children, controlling for family socioeconomic status, children's literacy score, working memory, and inhibition. More important, the experimental group children were more likely to tell prosocial lies than the control group, even after controlling for the pretest AToM and other covariates. However, the training effects faded at the 6-month follow-up test after the training's completion. These findings provide the first evidence for the causal role of AToM in the development of prosocial lie-telling in middle childhood. The fade-out effect is discussed in the context of educational interventions.

Caspase-3-Triggered Intracellular Gadolinium Nanoparticle Formation for T1-Weighted Magnetic Resonance Imaging of Apoptosis In Vivo.

Apoptosis, with a hallmark of upregulated protease Caspase-3, has been frequently imaged with various probes to reveal the therapeutic efficiencies of different drugs. However, activatable molecular probes with programmable self-assembling behaviors that enable enhanced T1-weighted magnetic resonance imaging (MRI) of apoptosis remain scarce. Herein, taking advantage of a CBT-Cys click reaction, we rationally designed a Caspase-3-activatable self-assembling probe Ac-Asp-Glu-Val-Asp-Cys(StBu)-Lys(DOTA(Gd))-CBT (DEVDCS-Gd-CBT) for apoptosis imaging in vivo. After Caspase-3 cleavage in apoptotic cells, DEVDCS-Gd-CBT underwent CBT-Cys click reaction to form a cyclic dimer, which self-assembled into Gd nanoparticles. With this probe, enhanced T1-weighted MR images of apoptosis were achieved at low magnetic fields in vitro, in cis-dichlorodiamineplatinum-induced apoptotic cells and in tail-amputation-simulated apoptotic zebrafish. We anticipate that the smart probe DEVDCS-Gd-CBT could be applied for T1-weighted MRI of apoptosis-related diseases in the clinic in the future.

Imaging Features of Primary Intraosseous Meningiomas.

OBJECTIVE: To describe the imaging features of primary intraosseous meningiomas (PIMs) to aid an accurate diagnosis. METHODS: Clinical materials and radiological data for 9 patients with pathologically confirmed PIMs were reviewed comprehensively. RESULTS: Most lesions involved inner and outer plates of the calvaria and all were relatively well circumscribed. Upon computed tomography, portions of the solid neoplasm were hyperattenuated or isoattenuated. Hyperostosis was found in many lesions, but calcification was seen rarely. On magnetic resonance imaging, most neoplasms were hypointense on T1-weighted images, hyperintense on T2-weighted images, and heterogeneous on fluid-attenuated inversion recovery images. In most cases, the soft tissue of neoplasms showed hyperintense on diffusion-weighted imaging and hypointense on apparent diffusion coefficient. All lesions were obviously enhanced after gadolinium administration. Each patient accepted surgical treatment and recurrence was not observed during follow-up. CONCLUSIONS: Primary intraosseous meningiomas are very rare tumors that occur usually in later life. They are well-defined and tend to involve the inner and outer plates of the calvaria, with a classic appearance of hyperostosis on computed tomography. Primary intraosseous meningiomas display hypointense on T1-weighted images, hyperintense on T2-weighted images, and hyperattenuated or isoattenuated on computed tomography. Hyperintense on diffusion-weighted imaging, hypointense on apparent diffusion coefficient can also be found. Obvious enhancement supplied additional information for an accurate diagnosis. A neoplasm with these features should raise the suspicion of a PIM.

Cultural background and input familiarity influence multisensory emotion perception.

OBJECTIVES: During multisensory emotion perception, the attention devoted to the visual versus the auditory modality (i.e., modality dominance) varies depending on the cultural background of the perceiver. In the present study, we examined (a) how cultural familiarity influences multisensory emotion perception in Eastern and Western cultures and (b) the underlying processes accounting for the cultural difference in modality dominance. METHOD: Native Mandarin speakers from China and native English speakers from the United States were presented with audiovisual emotional stimuli from their own culture (i.e., familiar) and from a different culture (i.e., unfamiliar) and asked to evaluate the emotion from one of the two modalities. Across modalities, the emotions were either the same (i.e., congruent, happy face, and happy voice) or different (i.e., incongruent, happy face, and sad voice). RESULTS: When the input was in a familiar cultural context, American participants were more influenced by the visual modality, while Chinese participants were more influenced by the auditory modality. While both groups integrated the incongruent emotion from the irrelevant modality, only the American group integrated the congruent emotion from the irrelevant modality. When the input was in a less familiar cultural context, both groups showed increased visual dominance, but only the Chinese group simultaneously showed decreased auditory dominance. CONCLUSIONS: We conclude that cultural background and input familiarity interact to influence modality dominance during multisensory emotion perception. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

ß-Catenin and SOX2 Interaction Regulate Visual Experience-Dependent Cell Homeostasis in the Developing Xenopus Thalamus.

In the vertebrate brain, sensory experience plays a crucial role in shaping thalamocortical connections for visual processing. However, it is still not clear how visual experience influences tissue homeostasis and neurogenesis in the developing thalamus. Here, we reported that the majority of SOX2-positive cells in the thalamus are differentiated neurons that receive visual inputs as early as stage 47 Xenopus. Visual deprivation (VD) for 2 days shifts the neurogenic balance toward proliferation at the expense of differentiation, which is accompanied by a reduction in nuclear-accumulated ß-catenin in SOX2-positive neurons. The knockdown of ß-catenin decreases the expression of SOX2 and increases the number of progenitor cells. Coimmunoprecipitation studies reveal the evolutionary conservation of strong interactions between ß-catenin and SOX2. These findings indicate that ß-catenin interacts with SOX2 to maintain homeostatic neurogenesis during thalamus development.

Enzyme-Instructed Aggregation/Dispersion of Fluorophores for Near-Infrared Fluorescence Imaging In Vivo.

Near-infrared (NIR) fluorescence is a noninvasive, highly sensitive, and high-resolution modality with great potential for in vivo imaging. Compared with "Always-On" probes, activatable NIR fluorescent probes with "Turn-Off/On" or "Ratiometric" fluorescent signals at target sites exhibit better signal-to-noise ratio (SNR), wherein enzymes are one of the ideal triggers for probe activation, which play vital roles in a variety of biological processes. In this review, we provide an overview of enzyme-activatable NIR fluorescent probes and concentrate on the design strategies and sensing mechanisms. We focus on the aggregation/dispersion state of fluorophores after the interaction of probes and enzymes and finally discuss the current challenges and provide some perspective ideas for the construction of enzyme-activatable NIR fluorescent probes.

[Mechanism of Jiaotai Pills in treatment of depression based on quantitative proteomics].

This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.

[Anti-depression mechanism of Zuojin Pills:based on UHPLC-TOF-MS, network pharmacology, and experimental verification].

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1ß, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.

Intracellular Synthesis of Hybrid Gallium-68 Nanoparticle Enhances MicroPET Tumor Imaging.

Positron-emission tomography (PET) imaging enables cancer diagnosis at an early stage and to determine its pathological degree. However, tumor uptake efficiency of traditional PET radiotracers is usually low. Herein, we rationally designed a precursor CBT-NODA, the cold analogue CBT-NODA-Ga, and its corresponding radiotracer CBT-NODA-68Ga. Using these three compounds, we verified that coinjection of CBT-NODA-68Ga with CBT-NODA or CBT-NODA-Ga could lead to the synthesis of hybrid gallium-68 nanoparticles in furin-overexpressing cancer cells and enhance microPET tumor imaging in mice. In vivo experiments showed that coinjection of CBT-NODA-68Ga with CBT-NODA-Ga had the most prolonged retention of the radiotracer in blood, the highest radioactivity in tumor regions, and the most enhanced microPET tumor imaging in mice. We anticipate that, by combining the coinjection strategy with our CBT-Cys click condensation reaction, more radiotracers are developed for microPET imaging of more tumors in clinical settings in the future.

Novel Hybrid Peptide Cathelicidin 2 (1-13)-Thymopentin (TP5) and Its Derived Peptides with Effective Antibacterial, Antibiofilm, and Anti-Adhesion Activities.

The increasing numbers of infections caused by multidrug-resistant (MDR) pathogens highlight the urgent need for new alternatives to conventional antibiotics. Antimicrobial peptides have the potential to be promising alternatives to antibiotics because of their effective bactericidal activity and highly selective toxicity. The present study was conducted to investigate the antibacterial, antibiofilm, and anti-adhesion activities of different CTP peptides (CTP: the original hybrid peptide cathelicidin 2 (1-13)-thymopentin (TP5); CTP-NH2: C-terminal amidated derivative of cathelicidin 2 (1-13)-TP5; CTPQ: glutamine added at the C-terminus of cathelicidin 2 (1-13)-TP5) by determining the minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), propidium iodide uptake, and analysis by scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy). The results showed that CTPs had broad-spectrum antibacterial activity against different gram-positive and gram-negative bacteria, with MICs against the tested strains varying from 2 to 64 µg/mL. CTPs at the MBC (2 × MIC 64 µg/mL) showed strong bactericidal effects on a standard methicillin-resistant Staphylococcus aureus strain ATCC 43300 after co-incubation for 6 h through disruption of the bacterial membrane. In addition, CTPs at 2 × MIC also displayed effective inhibition activity of several S. aureus strains with a 40-90% decrease in biofilm formation by killing the bacteria embedded in the biofilms. CTPs had low cytotoxicity on the intestinal porcine epithelial cell line (IPEC-J2) and could significantly decrease the rate of adhesion of S. aureus ATCC 43300 on IPEC-J2 cells. The current study proved that CTPs have effective antibacterial, antibiofilm, and anti-adhesion activities. Overall, this study contributes to our understanding of the possible antibacterial and antibiofilm mechanisms of CTPs, which might be an effective anti-MDR drug candidate.

Furin-Guided Intracellular 68Ga Nanoparticle Formation Enhancing Tumor MicroPET Imaging.

Positron-emission tomography (PET) is routinely used in the clinic for tumor imaging with ultrahigh sensitivity, but tumor-targeted PET imaging probes are quite few. In this work, we rationally designed a furin-responsive radiotracer Acetyl-Arg-Val-Arg-Arg-Cys(StBu)-Lys(DOTA-68Ga)-CBT (CBT-68Ga) and demonstrated that coinjection of the radiotracer with its cold analogue CBT-Ga instructed the formation of 68Ga nanoparticles in furin-overexpressing MDA-MB-468 cancer cells, which significantly enhanced microPET imaging of the tumor in vivo. In vitro results showed that CBT-Ga subjected to furin-initiated CBT-Cys condensation reaction and self-assembly to form the nanoparticles CBT-Ga-NPs with an average diameter of 258.3 nm. In vivo microPET imaging results indicate that the mice coinjected with CBT-68Ga and CBT-Ga, which warrants 68Ga nanoparticle formation in their MDA-MB-468 tumors, had a tumor/liver ratio 9.1-fold of that of the mice only injected with CBT-68Ga. We envisioned that, by replacing the RVRR substrate of CBT-68Ga with other enzyme-specific ones and using the strategy of intracellular nanoparticle formation, a series of radioactive probes could be developed for more sensitive and precise tumor microPET imaging in the near future.

Bioluminescent Turn-On Probe for Sensing Hypochlorite in Vitro and in Tumors.

Hypochlorite (ClO-) is one of the most important reactive oxygen species but using a BL probe for its selective detection (or imaging) still remains challenging. Herein, we report a latent BL probe benzoylhydrazine luciferin (1) for highly selective detection of ClO- in vitro and imaging ClO- in living cells and tumors. In vitro tests indicated that 1 could be applied for highly selective detection of ClO- within the range of 0-62.5 µM with a limit of detection of 0.705 µM. Using these unique features of 1, we successfully applied it to image ClO- in living cells and tumors. We envision that probe 1 might be applied to elucidate the biological roles of ClO- in wider physiological and pathological processes in the near future.

Choto-san versus placebo for patients with dementia: systematic review and meta-analysis.

BACKGROUND: Choto-san is a traditional medicine used for hypertension and headaches in Japan and China. Some studies have shown its effectiveness in the treatment of dementia. The present review aimed to assess the effectiveness and acceptability of Choto-san in the treatment of adults with cognitive impairment. METHODS: We included randomized controlled trials comparing Choto-san with placebo for patients with dementia or mild cognitive impairment. RESULTS: Three randomized controlled trials evaluating 219 participants were included. Two were studies on vascular dementia, and the other was on Alzheimer's dementia. There was no difference between Choto-san and placebo in terms of short-term dichotomous judgement of improvement, but Choto-san was more effective than placebo in terms of short-term improvement of cognitive function as measured by continuous outcomes. Also, dropouts judged it to be acceptable. However, the results were imprecise and/or heterogeneous. The number of participants included in the analysis was small (n = 199 in the primary analysis) and sometimes inconsistent, as indicated by the large I 2 (72% in the primary analysis). CONCLUSION: Low-quality evidence was suggestive of Choto-san's efficacy for vascular dementia, but the present results may be overestimated. Studies with a larger sample size and conducted over longer periods should be performed. Regardless, Choto-san can be one of the choices for the treatment of vascular dementia as it is well tolerated.

Cell Environment-Differentiated Self-Assembly of Nanofibers.

Employing cellular environment for the self-assembly of supramolecular nanofibers for biological applications has been widely explored. But using one precursor to differentiate the extra- and intracellular environments to self-assemble into two different nanofibers remains challenging. With the knowledge that the extracellualr environment of some cancer cells contains large amounts of alkaline phosphatase (ALP) while their intracellular environment is glutathione (GSH)-abundant in mind, we rationally designed a precursor Cys(SEt)-Glu-Tyr(H2PO3)-Phe-Phe-Gly-CBT (1) that can efficiently yield amphiphilic 2 and 2-D to self-assemble into two different nanofibers in hydrogels under the sequential treatment of ALP and GSH. We envision that, by employing a click condensation reaction, this work offers a platform for facilely postmodulation of supramolecular nanofibers, and the versatile precursor 1 could be used to kill two birds with one stone.

Nanocomputed Tomography Imaging of Bacterial Alkaline Phosphatase Activity with an Iodinated Hydrogelator.

Alkaline phosphatase (ALP) is an important enzyme, but direct imaging of ALP activity with high spatiotemporal resolution remains challenging. In this work, we rationally designed an iodinated hydrogelator precursor Nap-Phe-Phe(I)-Tyr(H2PO3)-OH (1P) which self-assembles into nanofibers to form hydrogel under the catalysis of ALP. With this property of concentrating iodine atoms at the locations of ALP, 1P was successfully applied for direct nanocomputed tomography (nano-CT) imaging of ALP activity in bacteria for the first time. We envision that, on the basis of this pioneering work, new hydrogelators containing more iodine atoms (e.g., five iodine atoms in 1P) will be designed for better nano-CT imaging of ALP activity with higher CT contrast in the near future.

Using "On/Off" (19)F NMR/Magnetic Resonance Imaging Signals to Sense Tyrosine Kinase/Phosphatase Activity in Vitro and in Cell Lysates.

Tyrosine kinase and phosphatase are two important, antagonistic enzymes in organisms. Development of noninvasive approach for sensing their activity with high spatial and temporal resolution remains challenging. Herein, we rationally designed a hydrogelator Nap-Phe-Phe(CF3)-Glu-Tyr-Ile-OH (1a) whose supramolecular hydrogel (i.e., Gel 1a) can be subjected to tyrosine kinase-directed disassembly, and its phosphate precursor Nap-Phe-Phe(CF3)-Glu-Tyr(H2PO3)-Ile-OH (1b), which can be subjected to alkaline phosphatase (ALP)-instructed self-assembly to form supramolecular hydrogel Gel 1b, respectively. Mechanic properties and internal fibrous networks of the hydrogels were characterized with rheology and cryo transmission electron microscopy (cryo-TEM). Disassembly/self-assembly of their corresponding supramolecular hydrogels conferring respective "On/Off" (19)F NMR/MRI signals were employed to sense the activity of these two important enzymes in vitro and in cell lysates for the first time. We anticipate that our new (19)F NMR/magnetic resonance imaging (MRI) method would facilitate pharmaceutical researchers to screen new inhibitors for these two enzymes without steric hindrance.