Understanding Staphylococcus aureus in hyperglycaemia: A review of virulence factor and metabolic adaptations.

Staphylococcus aureus is one of the most commonly detected bacteria in diabetic skin and soft tissue infections. The incidence and severity of skin and soft tissue infections are higher in patients with diabetes, indicating a potentiating mechanism of hyperglycaemia and infection. The goal of this review is to explore the metabolic and virulence factor adaptations of S. aureus under hyperglycaemic conditions. Primary data from identified studies were included and summarised in this paper. Understanding the nexus of hyperglycaemia, metabolism, and virulence factors provides insights into the complexity of diabetic skin and soft tissue infections attributed to S. aureus.

Spin crossover of a Fe(II) mononuclear complex induced by intermolecular factors involving chloride and solvent ordering.

Two new salts of a mononuclear tripodal Fe(II) complex were prepared, using ClO4- and Cl-. The ClO4- sample (1) remained HS at low temperatures, similar to the previously reported BF4- analogue. Crystallising with the Cl- anion (2) led to a markedly different crystal packing arrangement, and engendered SCO activity. This has been correlated to the lower crystal packing density in 2 and the coordination complex conformational differences arising due to the packing motifs of 1 and 2. Further, solvent ordering effects have been proposed to facilitate spin transition behaviour in 2.

Dual-Emissive Iridium(III) Complexes and Their Applications in Biological Sensing and Imaging.

Phosphorescent iridium(III) complexes are widely recognized for their unique properties in the excited triplet state, making them crucial for various applications including biological sensing and imaging. Most of these complexes display single phosphorescence emission from the lowest-lying triplet state after undergoing highly efficient intersystem crossing (ISC) and ultrafast internal conversion (IC) processes. However, in cases where these excited-state processes are restricted, the less common phenomenon of dual emission has been observed. This dual emission phenomenon presents an opportunity for developing biological probes and imaging agents with multiple emission bands of different wavelengths. Compared to intensity-based biosensing, where the existence and concentration of an analyte are indicated by the brightness of the probe, the emission profile response involves modifications in emission color. This enables quantification by utilizing the intensity ratio of different wavelengths, which is self-calibrating and unaffected by the probe concentration and excitation laser power. Moreover, dual-emissive probes have the potential to demonstrate distinct responses to multiple analytes at separate wavelengths, providing orthogonal detection capabilities. In this concept, we focus on iridium(III) complexes displaying fluorescence-phosphorescence or phosphorescence-phosphorescence dual emission, along with their applications as biological probes for sensing and imaging.

Cyclometalated Iridium(III) Complexes Containing Viologen-Modified Phenylpyridine Ligands as Electroluminochromic Active Molecules for Information Display.

Electroluminochromic (ELC) materials have garnered significant research interest because of their potential applications in lighting, displaying, and sensing. These materials exhibit reversible modulation of photoluminescence under low-voltage stimuli. Here five phosphorescent iridium(III) complexes are reported featuring viologen-substituted 2-phenylpyridine (Vppy) ligands acting as electroactive components. Four of the complexes are bis-cyclometalated and coordinated with either neutral bipyridine derivatives or negatively charged 2-picolinate. The remaining complex is heteroleptic tris-cyclometalated, containing one Vppy and two 2-phenylquinoline ligands. Upon photoexcitation, the bis-cyclometalated complexes exhibit orange to red phosphorescence originating from mixed triplet metal-to-ligand charge transfer (3MLCT) and intraligand (3IL) dπ(Ir)/π(Vppy) → π*(Vppy) state, whereas the tris-cyclometalated complex is non-emissive due to a low Ir(IV/III) oxidation potential favoring oxidative quenching by the viologen pendants. When the cationic viologens are electrochemically reduced to their neutral form, the bis-cyclometalated complexes show a remarkable blue-shift in their phosphorescence maxima due to increased energy levels of the Vppy molecular orbitals. In the case of the tris-cyclometalated complex, reduction of the viologen groups interrupts the quenching process, leading to a luminescence turn-on. These complexes are used to develop ELC devices, which exhibit reversible luminescence response in terms of color or on-off switching under a low voltage of 2 V.

Bioorthogonal dissociative rhenium(i) photosensitisers for controlled immunogenic cell death induction.

Photosensitisers for photoimmunotherapy with high spatiotemporal controllability are rare. In this work, we designed rhenium(i) polypyridine complexes modified with a tetrazine unit via a bioorthogonally activatable carbamate linker as bioorthogonally dissociative photosensitisers for the controlled induction of immunogenic cell death (ICD). The complexes displayed increased emission intensities and singlet oxygen (1O2) generation efficiencies upon reaction with trans-cyclooct-4-enol (TCO-OH) due to the separation of the quenching tetrazine unit from the rhenium(i) polypyridine core. One of the complexes containing a poly(ethylene glycol) (PEG) group exhibited negligible dark cytotoxicity but showed greatly enhanced (photo)cytotoxic activity towards TCO-OH-pretreated cells upon light irradiation. The reason is that TCO-OH allowed the synergistic release of the more cytotoxic rhenium(i) aminomethylpyridine complex and increased 1O2 generation. Importantly, the treatment induced a cascade of events, including lysosomal dysfunction, autophagy suppression and ICD. To the best of our knowledge, this is the very first example of using bioorthogonal dissociation reactions as a trigger to realise photoinduced ICD, opening up new avenues for the development of innovative photoimmunotherapeutic agents.

Luminescent iridium(III) porphyrin complexes as near-infrared-emissive biological probes.

We report herein the design, synthesis and characterisation of a series of luminescent iridium(III) porphyrin complexes [Ir(ttp)(CH2CH2OH)] (H2ttp = 5,10,15,20-tetra-4-tolylporphyrin) (1), [Ir(tpp-Ph-NO2)(CO)Cl] (H2tpp-Ph-NO2 = 5-(4-((4-nitrophenoxy)carbonyloxymethyl)phenyl)-10,15,20-triphenylporphyrin) (2), [Ir(tpp-COOMe)(Py)2](Cl) (H2tpp-COOMe = 5-(4-methoxycarbonylphenyl)-10,15,20-triphenylporphyrin; Py = pyridine) (3) and [Ir(tpp-COOH)(Py)2](Cl) (H2tpp-COOH = 5-(4-carboxylphenyl)-10,15,20-triphenylporphyrin) (4). All the complexes displayed long-lived near-infrared (NIR) emission attributed to an excited state of mixed triplet intraligand (3IL) (π → π*) (porphyrin) and triplet metal-to-ligand charge transfer (3MLCT) (dπ(Ir) → π*(porphyrin)) character. The cytotoxicity of the complexes toward HeLa cells was examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cationic complexes 3 and 4 exhibited higher cytotoxic activity toward HeLa cells than their neutral counterparts 1 and 2. Cellular uptake studies by inductively coupled plasma-mass spectrometry (ICP-MS) and laser-scanning confocal microscopy (LSCM) indicated that complexes 3 and 4 showed higher cellular uptake efficiencies than complexes 1 and 2 due to their cationic charge, and they were enriched in the perinuclear region of the cells with negligible nuclear uptake. Additionally, the carboxyl complex 4 was used to label a model protein bovine serum albumin (BSA) via an amidation reaction. The resultant luminescent protein conjugate 4-BSA displayed similar photophysical properties and intracellular localisation behaviour to its parent complex. The results of this work will contribute to the development of luminescent iridium(III) porphyrin complexes and related bioconjugates as NIR-emissive probes for bioimaging applications.

Dual-emissive Iridium(III) Complexes as Phosphorescent Probes with Orthogonal Responses to Analyte Binding and Oxygen Quenching.

Phosphorescent probes often show sensitive response toward analytes at a specific wavelength. However, oxygen quenching usually occurs at the same wavelength and thus hinders the accurate detection of analytes. In this study, we have developed dual-emissive iridium(III) complexes that exhibit phosphorescence responses to copper(II) ions at a wavelength distinct from that where oxygen quenching occurs. The complexes displayed colorimetric phosphorescence response in aqueous solutions under different copper(II) and oxygen conditions. In cellular imaging, variation in oxygen concentration over a large range from 5 % to 80 % can modulate the intensity and lifetime of green phosphorescence without affecting the response of red phosphorescence toward intracellular copper(II) ions.

Myrtinols A-F: New Anti-Inflammatory Peltogynoid Flavonoid Derivatives from the Leaves of Australian Indigenous Plant Backhousia myrtifolia.

Our in-house ethnopharmacological knowledge directed our anti-inflammatory investigation into the leaves of Backhousia mytifolia. Bioassay guided isolation of the Australian indigenous plant Backhousia myrtifolia led to the isolation of six new rare peltogynoid derivatives named myrtinols A-F (1-6) along with three known compounds 4-O-methylcedrusin (7), 7-O-methylcedrusin (8) and 8-demethylsideroxylin (9). The chemical structures of all the compounds were elucidated by detailed spectroscopic data analysis, and absolute configuration was established using X-ray crystallography analysis. All compounds were evaluated for their anti-inflammatory activity by assessing the inhibition of nitric oxide (NO) production and tumor necrosis factor- α (TNF-α) in lipopolysaccharide (LPS) and interferon (IFN)-γ activated RAW 264.7 macrophages. A structure activity relationship was also established between compounds (1-6), noting promising anti-inflammatory potential by compounds 5 and 9 with an IC50 value of 8.51 ± 0.47 and 8.30 ± 0.96 µg/mL for NO inhibition and 17.21 ± 0.22 and 46.79 ± 5.87 µg/mL for TNF-α inhibition, respectively.

Positive Psychology Themes in Interviews of Children With Atopic Dermatitis: Qualitative Study.

BACKGROUND: Atopic dermatitis is a pruritic chronic condition associated with significant sleep disturbance, inattention, and sometimes behavioral problems. Enhancing resiliency in children with atopic dermatitis may promote coping strategies to improve quality of life. Positive psychology is one strategy that can be used to strengthen resiliency. OBJECTIVE: Our objective was to identify positive psychology concepts mentioned by children with atopic dermatitis and their parent to inform strategies to strengthen resiliency in children with atopic dermatitis. METHODS: A total of 20 patient-parent dyads were interviewed to share their experience with atopic dermatitis to help develop a novel psychologic intervention for atopic dermatitis. Patients were 8 to 17 years old and diagnosed with atopic dermatitis. Trained coders analyzed transcripts using a coding dictionary developed based on Seligman's PERMA (positive emotion, engagement, relationships, meaning, and accomplishment) model of positive psychology. The frequency of unprompted mentions of PERMA themes and relevant quotations was captured. Transcripts were also separately coded for resiliency, which is the ultimate goal of PERMA. RESULTS: Positive psychology concepts were mentioned by 100% (20/20) of children and 95% (19/20) of parents. Engagement and relationships, both negative and positive aspects, were the most common unprompted PERMA themes mentioned by children (14/20, 70%) and parents (13/20, 65%). Emotion elicited the most negative comments from children (19/20, 95%) and parents (17/20, 85%). When analyzed for resiliency, 8 participants were identified with at least one resiliency code. On average, participants with a resiliency code mentioned PERMA concepts 9.1 (SD 4.7) times compared to those who mentioned none (mean 5.9, SD 4.6) (P=.14). When participants were stratified by disease severity, on average, more positive psychology concepts were mentioned by patients with mild atopic dermatitis (mean 13, SD 3.0) than those with moderate symptoms (mean 6.2, SD 4.9) or severe symptoms (mean 6.1, SD 4.0) (P=.03). CONCLUSIONS: Among PERMA themes, engagement and relationships are the two most commonly mentioned categories for children with atopic dermatitis. Strategies targeting PERMA such as affirmations and positive reframing may improve psychosocial well-being and resiliency in pediatric atopic dermatitis. Future directions will look at incorporating "positive medicine" into atopic dermatitis treatment to not only relieve symptoms but also strengthen positive aspects of life.

A review on the biological, epidemiological, and statistical relevance of COVID-19 paired with air pollution.

This narrative review paper is aimed to critically evaluate recent studies of the associations between air pollution and the outcomes in the COVID-19 pandemic. The main air pollutants we have considered are carbon monoxide (CO), nitrogen dioxide (NO2), ground-level ozone (O3), particulate matter (PM2.5 and PM10), and sulfur dioxide (SO2). We, specifically, evaluated the influences of these pollutants, both individually and collaboratively, across various geographic areas and exposure windows. We further reviewed the proposed biological mechanisms underlying the association between air pollution and COVID-19. Ultimately, we aim to inform policy and public health practice regarding the implications of COVID-19 and air pollution.

Cellular imaging properties of phosphorescent iridium(III) complexes substituted with ester or amide groups.

Phosphorescent iridium(III) complexes have been extensively investigated as cellular imaging reagents and sensors. The intracellular localization of the complexes is known to be closely related to their formal charge, molecular size, lipophilicity, and bioactive pendants. Herein, we reported four phosphorescent iridium(III) complexes with the diimine ligands being modified with ester or amide groups as imaging reagents for living cells. The complexes have the same positive charge and very similar molecular size and weight. The lipophilicity of the complexes is similar ranging from 1.45 to 2.14. Upon internalization into living HeLa cells, while complexes 2-4, like most other iridium(III) complexes, were localized in the cytoplasm, complex 1 unexpectedly stained the whole cells including nuclei. The nuclear uptake of complex 1 was not observed when the cells were pretreated with chlorpromazine or nocodazole, suggesting that clathrin and microtubules mediated the nuclear uptake of complex 1. Additionally, the nuclear uptake efficiency is related to the cell division cycle. The complex was mainly concentrated in the nucleus when the cells were in mitosis, and distributed in whole cells when the cells were in the interphases. Furthermore, complex 1 exhibited a longer luminescence lifetime in the nucleus than in the cytoplasm as revealed by photoluminescence lifetime imaging microscopy (PLIM). Incubation of the cells in the hypoxia environment elongated the lifetime of the cytoplasmic complex, but hardly affected the luminescence properties of the intranuclear complex.

Evidence synthesis evaluating body weight gain among people treating HIV with antiretroviral therapy - a systematic literature review and network meta-analysis.

Background: This systematic review aimed to compare body weight gain associated outcomes over time between dolutegravir (DTG)-based antiretroviral (ART) regimens to other ART regimens, to compare tenofovir alafenamide (TAF)-based regimens, and to evaluate the associated prognostic factors. Methods: Systematic searches of MEDLINE, Embase, and CENTRAL for RCTs and observational studies comparing ART regimens were conducted on 13 September 2021. Outcomes of interest included: change in body weight, body mass index (BMI), waist circumference; and risk of hyperglycaemia and diabetes. Network meta-analyses were conducted at 12, 24, 48, 96 and 144 weeks using two networks differentiated by 3rd agents and backbone agents. Findings: The review identified 113 publications reporting on 73 studies. DTG-based regimens led to statistically higher weight gains than efavirenz-based regimens at all time points (mean difference: 1·99 kg at 96 weeks; 95% credible interval: 0·85-3·09) and was higher over time than low-dose efavirenz-, elvitegravir-, and rilpivirine-based regimens. They were comparable to raltegravir-, bictegravir- and atazanavir-based regimens. For backbones, TAF led to higher weight gain relative to tenofovir disoproxil fumarate (TDF), abacavir, and zidovudine. Prognostic factor analysis showed both low CD4 cell count and high HIV RNA viral load at baseline were consistently associated with higher weight gain, while sex was an effect modifier to African origins. Interpretation: DTG-based regimens lead to larger average weight gains than some other ART regimens and TAF leads to larger average weight gains than all other backbone antiretrovirals. Further research is needed to better understand long-term outcomes and their relationship to other metabolic outcomes. Funding: The WHO Global HIV, Hepatitis and Sexually Transmitted Infections Programmes.

Dual-lifetime luminescent probe for time-resolved ratiometric oxygen sensing and imaging.

Fluorescent/phosphorescent dual-emissive polymers or hybrids consisting of both fluorophore and phosphor have been used as self-calibrating probes and imaging reagents for cellular molecular oxygen. Oxygen selectively quenches the phosphorescence and the fluorescence serves as an internal reference. The phosphorescence/fluorescence ratio is used as a quantitative indicator of oxygen content. In wavelength-ratiometric probes, the fluorophore and phosphor are designed to emit at different wavelengths. It is easy to achieve spectral separation, but the phosphorescence/fluorescence ratio fluctuates due to the difference in the absorption and scattering of light at different wavelengths by biological samples. Herein we reported a lifetime-ratiometric luminescent polymeric probe where the fluorophore and phosphor emitted at the same wavelength. Spectral separation was achieved based on the difference in their excited-state lifetimes via time-resolved luminescence analysis and imaging. The probe exhibited a phosphorescence lifetime of about 931 ns with a phosphorescence/fluorescence ratio of 4.49 in deaerated aqueous buffer. The lifetime was shortened to 251 ns and the ratio decreased to 1.08 in oxygen saturated solution because of phosphorescence quenching. The utilization of the probe for quantitative oxygen sensing and mapping in living HeLa cells was demonstrated using calibration curves obtained from fixed cells.

Manipulating Electroluminochromism Behavior of Viologen-Substituted Iridium(III) Complexes through Ligand Engineering for Information Display and Encryption.

Electrically controlling photoluminescence has attracted great research interest and offers many opportunities for technological developments. Electroluminochromic materials undergo redox reactions under low-voltage stimuli to achieve reversible luminescence switching. Till now, photoluminescence switching of a single molecule caused by electrical stimuli is restricted to intensity response because the redox-active moieties are good electron donors or acceptors and electrical stimuli can regulate the photoinduced electron-transfer and affect the luminescence intensity. In this work, the manipulation of the electroluminochromism behavior of a series of viologen-substituted iridium(III) complexes through the regulation of ligand orbital energy levels and electronic communication between the viologen pendants and the iridium(III) complex core is reported. Electrochemical redox reactions reversibly modulate either the luminescence quenching effect or the push-pull electronic effect of the viologen substituents, achieving multicolor "on-off" luminescence response toward electrical stimuli and luminescence manipulation between two emissive states with different wavelengths and lifetimes. To illustrate the promising applications of these electroluminochromic materials, recording and displaying luminescence information under electrical stimuli are demonstrated. Information encryption is realized by letting the electroluminochromism occur in the near-infrared region or in the time domain. Near-infrared camera or time-resolved luminescence analysis can be used to help read the invisible information.

Time-resolved analysis of photoluminescence at a single wavelength for ratiometric and multiplex biosensing and bioimaging.

Simultaneous analysis of luminescence signals of multiple probes can improve the accuracy and efficiency of biosensing and bioimaging. Analysis of multiple signals at different wavelengths usually suffers from spectral overlap, possible energy transfer, and difference in detection efficiency. Herein, we reported a polymeric luminescent probe, which was composed of a phenothiazine-based fluorescent compound and a phosphorescent iridium(iii) complex. Both luminophores emitted at around 600 nm but their luminescence lifetimes are 160 times different, allowing time-resolved independent analysis. As the fluorescence was enhanced in response to oxidation by hypochlorite and the phosphorescence was sensitive toward oxygen quenching, a four-dimensional relationship between luminescence intensity, fluorescence/phosphorescence ratio, hypochlorite concentration, and oxygen content was established. In cellular imaging, time-resolved photoluminescence imaging microscopy clearly showed the independent fluorescence response toward hypochlorite and phosphorescence response toward oxygen in separated time intervals. This work opens up a new idea for the development of multiplex biosensing and bioimaging.

Lag time between state-level policy interventions and change points in COVID-19 outcomes in the United States.

State-level policy interventions have been critical in managing the spread of the new coronavirus. Here, we study the lag time between policy interventions and change in COVID-19 outcome trajectory in the United States. We develop a stepwise drifts random walk model to account for non-stationarity and strong temporal correlation and subsequently apply a change-point detection algorithm to estimate the number and times of change points in the COVID-19 outcome data. Furthermore, we harmonize data on the estimated change points with non-pharmaceutical interventions adopted by each state of the United States, which provides us insights regarding the lag time between the enactment of a policy and its effect on COVID-19 outcomes. We present the estimated change points for each state and the District of Columbia and find five different emerging trajectory patterns. We also provide insight into the lag time between the enactment of a policy and its effect on COVID-19 outcomes.

Association of temporary Environmental Protection Agency regulation suspension with industrial economic viability and local air quality in California, United States.

BACKGROUND: This study seeks to answer two questions about the impacts of the 2020 Environmental Protection Agency's enforcement regulation rollbacks: is this suspension bolstering the economic viability of industries as oil and manufacturing executives claim they will and are these regulations upholding the agency's mission of protecting the environment? RESULTS: To answer the former question, we utilized 6 months of state employment level data from California, United States, as a method of gauging the economic health of agency-regulated industries. We implemented a machine learning model to predict weekly employment data and a t-test to indicate any significant changes in employment. We found that, following California's state-issued stay-at-home order and the agency's regulation suspension, oil and certain manufacturing industries had statistically significant lower employment values.To answer the latter question, we used 10 years of PM2.5 levels in California, United States, as a metric for local air quality and treatment-control county pairs to isolate the impact of regulation rollbacks from the impacts of the state lockdown. Using the agency's data, we performed a t-test to determine whether treatment-control county pairs experienced a significant change in PM2.5 levels. Even with the statewide lockdown-a measure we hypothesized would correlate with decreased mobility and pollution levels-in place, counties with oil refineries experienced the same air pollution levels when compared to historical data averaged from the years 2009 to 2019. CONCLUSIONS: In contrast to the expectation that the suspension would improve the financial health of the oil and manufacturing industry, we can conclude that these industries are not witnessing economic growth with the suspension and state shutdown in place. Additionally, counties with oil refineries could be taking advantage of these rollbacks to continue emitting the same amount of PM2.5, in spite of state lockdowns. For these reasons, we ask international policymakers to reconsider the suspension of enforcement regulations as these actions do not fulfill their initial expectations. We recommend the creation and maintenance of pollution control and prevention programs that develop emission baselines, mandate the construction of pollution databases, and update records of pollution emissions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12302-021-00489-9.

Cyclometalated iridium(III) complexes containing an anthracene unit for sensing and imaging singlet oxygen in cellular mitochondria.

Singlet oxygen (1O2), as a highly reactive oxygen species, plays an important role in the physical, chemical and biomedical fields, especially during photodynamic therapy (PDT) process. In this work, two iridium(III) complexes containing an anthracene unit in their diimine ligand were designed and synthesized to monitor 1O2 in living cells. The complexes were weakly emissive owing to the photoinduced electron transfer process, but exhibited intense luminescence upon capturing 1O2, resulting from the formation of the corresponding endoperoxide analogues. The remarkable turn-on luminescence response was specific toward 1O2 and in preference to other reactive oxygen species. The utilization of one of the complexes for imaging 1O2 in living cells has also been demonstrated using three different cells lines. Cells incubated with the complexes were hardly emissive. Further light irradiation at 475 nm triggered intracellular emission turn on, indicative of the production of 1O2 photochemically. The emissive pattern was well colocalized with commercially available MitoTracker, suggesting the potential applications of the complexes for imaging mitochondria 1O2. The 1O2 capturing properties rendered the complexes low photocytotoxicity since 1O2-caused oxidative damage toward cellular molecules and structures was inhibited.

Thermally activated triplet exciton release for highly efficient tri-mode organic afterglow.

Developing high-efficient afterglow from metal-free organic molecules remains a formidable challenge due to the intrinsically spin-forbidden phosphorescence emission nature of organic afterglow, and only a few examples exhibit afterglow efficiency over 10%. Here, we demonstrate that the organic afterglow can be enhanced dramatically by thermally activated processes to release the excitons on the stabilized triplet state (T1*) to the lowest triplet state (T1) and to the singlet excited state (S1) for spin-allowed emission. Designed in a twisted donor-acceptor architecture with small singlet-triplet splitting energy and shallow exciton trapping depth, the thermally activated organic afterglow shows an efficiency up to 45%. This afterglow is an extraordinary tri-mode emission at room temperature from the radiative decays of S1, T1, and T1*. With the highest afterglow efficiency reported so far, the tri-mode afterglow represents an important concept advance in designing high-efficient organic afterglow materials through facilitating thermally activated release of stabilized triplet excitons.

Bioorthogonal "Labeling after Recognition" Affording an FRET-Based Luminescent Probe for Detecting and Imaging Caspase-3 via Photoluminescence Lifetime Imaging.

Bis-labeling with a luminescent energy donor/acceptor pair onto biological substrates affords probes which give FRET readouts for the detection of interaction partners. However, the covalently bound luminophores bring about steric hindrance and nonspecific interaction, which probably perturb the biological recognition. Herein, we designed a highly sensitive and specific "labeling after recognition" sensing approach, where luminophore labeling occurred after the biological recognition. Taking the cutting enzyme caspase-3 as an example, we demonstrated the detection of its catalytic activity in solution and apoptotic cells using the tetrapeptide motif Asp-Glu-Val-Asp (DEVD) as the cleavable substrate, and an iridium(III) complex and a rhodamine derivative as the energy donor/acceptor pair. The DEVD tetrapeptide was modified with an azide and a GK-norbornylene groups at the amino and carboxyl terminuses, respectively, which allowed donor/acceptor bis-labeling via two independent catalysis-free bioorthogonal reactions. The phosphorescence lifetime of the iridium(III) complex was quenched upon bis-labeling owing to the intracellular FRET to the rhodamine derivative, and significantly elongated upon the peptide being catalytically cleaved by caspase-3. Interestingly, the sensitivity and efficiency of the lifetime responses were much higher in the "labeling after recognition" sensing approach. Molecular docking analysis showed that the steric hindrance and nonspecific interactions partially inhibited the biological recognition of the DEVD substrate by caspase-3. The imaging of the catalytic activity of caspase-3 in apoptotic cells was demonstrated via photoluminescence lifetime imaging microscopy. Lifetime analysis not only confirmed the occurrence of intracellular bioorthogonal bis-labeling and catalytic cleavage, but also showed the extent to which the two dynamic processes occurred.