Opioid use patterns following discharge from elective colorectal surgery: a prospective cohort study.

INTRODUCTION: Opioid overprescription after colorectal surgery can lead to adverse events, persistent opioid use, and diversion of unused pills. This study aims to assess the extent to which opioids prescribed at discharge after elective colorectal surgery are consumed by patients. METHODS: This prospective cohort study included adult patients (≥ 18 yo) undergoing elective colorectal surgery at two academic hospitals in Montreal, Canada. Patients completed preoperative questionnaires and data concerning demographics, surgical details, and perioperative care characteristics (including discharge prescriptions) were extracted from electronic medical records. Self-reported opioid consumption was assessed weekly up to 1-month post-discharge. The total number of opioid pills prescribed and consumed after discharge were compared using the Wilcoxon signed-rank test. Negative binomial regression was used to identify predictors of opioid consumption. RESULTS: We analyzed 344 patients (58 ± 15 years, 47% female, 65% laparoscopic, 31% rectal resection, median hospital stay 3 days [IQR 1-5], 18% same-day discharge). Most patients received a TAP block (67%). Analgesia prescription at discharge included acetaminophen (92%), NSAIDs (38%), and opioids (92%). The quantity of opioids prescribed at discharge (median 13 pills [IQR 7-20]) was significantly higher than patient-reported consumption at one month (median 0 pills [IQR 0-7]) (p < 0.001). Overall, 51% of patients did not consume any opioids post-discharge, and 63% of the prescribed pills were not used. Increased opioid consumption was associated with younger age (IRR 0.99 [95%CI 0.98-0.99]), higher preoperative anxiety (1.02 [95%CI 1.00-1.04]), rectal resections (IRR 1.45 [95%CI 1.09-1.94]), and number of pills prescribed (1.02 [95%CI 1.01-1.03]). CONCLUSION: A considerable number of opioid pills prescribed at discharge after elective colorectal surgery are left unused by patients. Certain patient and care characteristics were associated with increased opioid consumption. Our findings indicate that post-discharge analgesia with minimal or no opioids may be feasible and warrants further investigation.

Leveraging the Photofunctions of Transition Metal Complexes for the Design of Innovative Phototherapeutics.

Despite the advent of various medical interventions for cancer treatment, the disease continues to pose a formidable global health challenge, necessitating the development of new therapeutic approaches for more effective treatment outcomes. Photodynamic therapy (PDT), which utilizes light to activate a photosensitizer to produce cytotoxic reactive oxygen species (ROS) for eradicating cancer cells, has emerged as a promising approach for cancer treatment due to its high spatiotemporal precision and minimal invasiveness. However, the widespread clinical use of PDT faces several challenges, including the inefficient production of ROS in the hypoxic tumor microenvironment, the limited penetration depth of light in biological tissues, and the inadequate accumulation of photosensitizers at the tumor site. Over the past decade, there has been increasing interest in the utilization of photofunctional transition metal complexes as photosensitizers for PDT applications due to their intriguing photophysical and photochemical properties. This review provides an overview of the current design strategies used in the development of transition metal complexes as innovative phototherapeutics, aiming to address the limitations associated with PDT and achieve more effective treatment outcomes. The current challenges and future perspectives on the clinical translation of transition metal complexes are also discussed.

Potent BODIPY-based photosensitisers for selective mitochondrial dysfunction and effective photodynamic therapy.

The development of new and improved mitochondria-targeting photosensitisers (PSs) for photodynamic therapy (PDT) remains highly desirable, due to the critical role the mitochondria play in maintaining healthy cellular function. Here, we report the design, synthesis, photophysical properties and biological characterisation of a series of di-iodinated BODIPY-based PSs, BODIPY-Mito-I-n, for mitochondria-targeted PDT applications. Six BODIPY-Mito-I-n analogues were synthesised in good yields, with fast reaction times of between 30 and 60 min under mild conditions. The di-iodination of the BODIPY scaffold enabled highly efficient population of the triplet state, leading to high singlet oxygen (1O2) photosensitisation efficiencies (ΦΔ = 0.55-0.65). All BODIPY-Mito-I-n compounds exhibited very high photocytotoxic activity towards HeLa cells, with IC50,light values of between 1.30 and 6.93 nM, due to photoinduced 1O2 generation. Notably, the poly(ethylene glycol) (PEG)-modified BODIPY-Mito-I-6 showed remarkably lower dark cytotoxicity (IC50,dark = 6.68-7.25 µM) than the non-PEGylated analogues BODIPY-Mito-I-1 to BODIPY-Mito-I-5 (IC50,dark = 0.58-1.09 µM), resulting in photocytotoxicity indices up to 2120. Mechanistic studies revealed that BODIPY-Mito-I-6 induced reactive oxygen species overproduction and mitochondrial dysfunction in cells upon irradiation, leading to significant cell death through a combination of apoptosis and necrosis. It is anticipated that our design will contribute to the development of more effective mitochondria-targeting PSs for cancer therapy.

Exploiting the Potential of Iridium(III) bis-Nitrone Complexes as Phosphorogenic Bifunctional Reagents for Phototheranostics.

Cross-linking strategies have found wide applications in chemical biology, enabling the labeling of biomolecules and monitoring of protein-protein interactions. Nitrone exhibits remarkable versatility and applicability in bioorthogonal labeling due to its high reactivity with strained alkynes via the strain-promoted alkyne-nitrone cycloaddition (SPANC) reaction. In this work, four cyclometalated iridium(III) polypyridine complexes functionalized with two nitrone units were designed as novel phosphorogenic bioorthogonal reagents for bioimaging and phototherapeutics. The complexes showed efficient emission quenching, which is attributed to an efficient nonradiative decay pathway via the low-lying T1/S0 minimum energy crossing point (MECP), as revealed by computational studies. However, the complexes displayed significant emission enhancement and lifetime extension upon reaction with (1R,8S,9s)-bicyclo[6.1.0]non-4-yne (BCN) derivatives. In particular, they showed a remarkably higher reaction rate toward a bis-cyclooctyne derivative (bis-BCN) compared with its monomeric counterpart (mono-BCN). Live-cell imaging and (photo)cytotoxicity studies revealed higher photocytotoxicity in bis-BCN-pretreated cells, which is ascribed to the enhanced singlet oxygen (1O2) photosensitization resulting from the elimination of the nitrone-associated quenching pathway. Importantly, the cross-linking properties and enhanced reactivity of the complexes make them highly promising candidates for the development of hydrogels and stapled/cyclized peptides, offering intriguing photophysical, photochemical, and biological properties. Notably, a nanosized hydrogel (2-gel) demonstrated potential as a drug delivery system, while a stapled peptide (2-bis-pDIKK) exhibited p53-Mdm2 inhibitory activity related to apoptosis and a cyclized peptide (2-bis-RGD) showed cancer selectivity.

Association between patient activation and adherence to a colorectal enhanced recovery pathway: a prospective cohort study.

BACKGROUND: Low adherence to enhanced recovery pathways (ERPs) may negatively affect postoperative outcomes. The objective of this study was to assess the extent to which patient activation (PA, i.e., knowledge, skills, and confidence to participate in care) is associated with adherence to an ERP for colorectal surgery. METHODS AND PROCEDURES: This cohort study included adult patients (≥ 18 yo) undergoing in-patient elective colorectal surgery at two university-affiliated hospitals in Montreal, Canada. Preoperatively, patients completed the Patient Activation Measure (PAM) questionnaire (score 0-100, categorized into low PA [≤ 55.1] vs. high PA [≥ 55.2]). All patients were managed with an ERP including 15 interventions classified into 2 groups: those requiring active patient participation (5 active ERP interventions, including early oral intake and mobilization) and those directed by the clinical team (10 passive ERP interventions, including early termination of IV fluids and urinary drainage). The adjusted association between PA and ERP adherence was evaluated using linear regression. RESULTS: A total of 286 patients were included (mean age 59 ± 15 years, 45% female, 62% laparoscopic, 33% rectal, median length of stay 4 days [IQR 2-6]). Most patients had high levels of PA (74%). Mean adherence was 90% (95% CI 88-91%) for passive ERP interventions and 72% (95% CI 70-75%) for active interventions. On regression analysis, high PA was associated with increased adherence to active ERP interventions (+ 6.8% [95% CI + 1.1 to + 12.5%]), but not to passive interventions (+ 2.5% [95% CI - 0.3 to + 5.3%]). Increased active ERP adherence was associated with reduced length of stay, 30-day complications, and hospital readmissions. CONCLUSION: This study supports that high PA is associated with increased adherence to ERP interventions, particularly those requiring active patient participation. Preoperative identification of patients with low activation may inform interventions to optimize patient involvement with ERPs and improve postoperative outcomes.

Diagnostic and Therapeutic Implications of a FUS::TFCP2 Fusion and ALK Activation in a Metastatic Rhabdomyosarcoma.

The identification of gene fusions in rare sarcoma subtypes can have diagnostic, prognostic, and therapeutic impacts for advanced cancer patients. Here, we present a case of a 31-year-old male with a lytic lesion of the left mandible initially diagnosed as an osteosarcoma but found to have a TFCP2 fusion and ALK alteration, redefining the diagnosis and providing rationale for a novel treatment strategy. Histologically, the tumor displayed hypercellular, spindled to epithelioid neoplasm and nuclear pleomorphism, while immunohistochemistry showed diffuse SATB2 and focal desmin staining. Whole genome and transcriptome analysis revealed a FUS::TFCP2 fusion, the defining alteration of a rare molecularly characterized subtype of soft tissue sarcoma termed intraosseous rhabdomyosarcoma. An internal ALK deletion and extremely high ALK RNA expression were also identified, suggesting potential benefit of an ALK inhibitor. This patient displayed a rapid and dramatic clinical and radiographic response to an ALK inhibitor, alectinib. Unfortunately, the response was short-lived, likely due to the advanced stage and aggressiveness of the disease. This report describes genome and transcriptome characterization of an intraosseous rhabdomyosarcoma, few of which exist in the literature, as well as providing evidence that inhibition of ALK may be a rational treatment strategy for patients with this exceedingly rare soft tissue sarcoma subtype characterized by TFCP2 fusions and ALK activation.

Upcycling of Spent LiFePO4 Cathodes to Heterostructured Electrocatalysts for Stable Direct Seawater Splitting.

The pursuit of carbon-neutral energy has intensified the interest in green hydrogen production from direct seawater electrolysis, given the scarcity of freshwater resources. While Ni-based catalysts are known for their robust activity in alkaline water oxidation, their catalytic sites are prone to rapid degradation in the chlorine-rich environments of seawater, leading to limited operation time. Herein, we report a Ni(OH)2 catalyst interfaced with laser-ablated LiFePO4 (Ni(OH)2/L-LFP), derived from spent Li-ion batteries (LIBs), as an effective and stable electrocatalyst for direct seawater oxidation. Our comprehensive analyses reveal that the PO4 3- species, formed around L-LFP, effectively repels Cl- ions during seawater oxidation, mitigating corrosion. Simultaneously, the interface between in situ generated NiOOH and Fe3(PO4)2 enhances OH- adsorption and electron transfer during the oxygen evolution reaction. This synergistic effect leads to a low overpotential of 237 mV to attain a current density of 10 mA cm-2 and remarkable durability, with only a 3.3 % activity loss after 600 h at 100 mA cm-2 in alkaline seawater. Our findings present a viable strategy for repurposing spent LIBs into high-performance catalysts for sustainable seawater electrolysis, contributing to the advancement of green hydrogen production technologies.

Patient perspective on adapting to bowel dysfunction after rectal cancer surgery.

AIM: Bowel dysfunction continues to be a clinically significant consequence of rectal cancer surgery, affecting quality of life. Rectal cancer patients value self-empowerment and adaptation to change to improve their quality of life in the context of bowel dysfunction. There are limited qualitative data addressing patients' perspectives on adapting to bowel dysfunction. The aim of this study is to evaluate patients' perspectives on adapting to bowel dysfunction after rectal cancer surgery. METHOD: Adult patients who underwent rectal cancer surgery with sphincter preservation at a single colorectal referral centre from July 2017 to July 2020 were included. Patients were excluded if they had surgery <1 year since recruitment, received a permanent stoma or developed recurrence or metastasis. Semistructured interviews were held by phone and transcribed verbatim. Bowel dysfunction was assessed via the low anterior resection syndrome (LARS) score. Thematic analysis was used to identify adaptations which patients found helpful for improving bowel dysfunction after rectal cancer surgery. RESULTS: A total of 54 patient interviews were included. The distribution of patients with no, minor and major LARS was 39%, 22% and 39%, respectively. Four main themes were conceived from the analysis: implementing lifestyle changes, fostering supportive relationships and self-compassion, communication and access to resources, and adapting to social and cultural challenges. Associated subthemes were identified, namely forward planning, self-compassion and addressing social stigma. CONCLUSION: Patients' valuable perspective on adapting to bowel dysfunction involve subtle themes which expand the existing literature. These themes inform a patient-centred approach, which may improve outcomes and quality of care for rectal cancer patients.

Photoreforming of Microplastics: Challenges and Opportunities for Sustainable Environmental Remediation.

Plastics are widely used in daily lives, but unfortunately, their inadequate recycling practices have led to the accumulation of microplastics in the environment, posing a threat to public health. The existing methods for treating microplastics are energy-intensive and environmentally damaging. In this context, photoreforming has emerged as a sustainable solution to address the microplastic crisis by simultaneously recycling them into value-added chemicals. This review presents a comprehensive overview of the application of photoreforming for upcycling microplastic. The underlying mechanisms of photoreforming reaction are discussed, followed by the exploration of recent advancements and innovative strategies in photoreforming techniques with particular emphasis on their real-world applications and potential for large-scale implementation. Also, critical factors influencing the efficiency of microplastic photoreforming are identified, providing guidance for further research and optimization.

Decision-making preferences and regret in rectal cancer patients undergoing restorative proctectomy: A prospective cohort study.

BACKGROUND: How patients make treatment choices in rectal cancer is poorly understood and may affect long-term regret and satisfaction. The objective of this study is to characterize decision-making preferences and their effect on decisional regret in patients undergoing restorative proctectomy for rectal cancer. METHODS: A prospective cohort study was conducted in a single academic specialist rectal cancer center from October 2018 to June 2022. Adult patients who underwent restorative proctectomy at least one year prior were recruited. Health literacy was assessed using the BRIEF instrument. Decision-making preferences regarding cancer treatment were assessed using the Control Preferences Scale. Decisional regret regarding their choice of restorative proctectomy was assessed using the Decision Regret Score. Bowel dysfunction was measured using the low anterior resection syndrome score. RESULTS: Overall, 123 patients were included. Health literacy was categorized as adequate in 63%, marginal in 25%, and limited in 12%. Patients with adequate health literacy were more likely to prefer a collaborative decision-making role compared with those with low health literacy (86% vs 65%, P = .016). Patients with incongruence between preferred and actual decision-making roles were more likely to report high regret (56% vs 25%, P = .003). Patients with major low anterior resection syndrome were also more likely to experience high regret compared with patients with no/minor low anterior resection syndrome (44% vs 25%, P = .036). CONCLUSION: A significant proportion of patients with rectal cancer undergoing restorative proctectomy do not have a decision-making role that is congruent with their preferences, and these patients experience a high degree of regret.

Amphipathic Surfactant on Reconstructed Bismuth Enables Industrial-Level Electroreduction of CO2 to Formate.

Developing efficient electrocatalysts for selective formate production via the electrochemical CO2 reduction reaction (CO2RR) is challenged by high overpotential, a narrow potential window of high Faradaic efficiency (FEformate), and limited current density (Jformate). Herein, we report a hierarchical BiOBr (CT/h-BiOBr) with surface-anchored cetyltrimethylammonium bromide (CTAB) for formate-selective large-scale CO2RR electrocatalysis. CT/h-BiOBr achieves over 90% FEformate across a wide potential range (-0.5 to -1.1 V) and an industrial-level Jformate surpassing 100 mA·cm-2 at -0.7 V. In situ investigations uncover the reconstructed Bi(110) surface as the active phase, with CTAB playing a dual role: its hydrophobic alkyl chains create a CO2-enriching microenvironment, while its polar head groups fine-tune the electronic structure, fostering a highly active phase. This work provides valuable insights into the role of surfactants in electrocatalysis and guides the design of electrocatalysts for the large-scale CO2RR.

Waste plastics upcycled for high-efficiency H2O2 production and lithium recovery via Ni-Co/carbon nanotubes composites.

The disposal and management of waste lithium-ion batteries (LIBs) and low-density polyethylene (LDPE) plastics pose significant environmental challenges. Here we show a synergistic pyrolysis approach that employs spent lithium transition metal oxides and waste LDPE plastics in one sealed reactor to achieve the separation of Li and transition metal. Additionally, we demonstrate the preparation of nanoscale NiCo alloy@carbon nanotubes (CNTs) through co-pyrolysis of LiNi0.6Co0.2Mn0.2O2 and LDPE. The NiCo alloy@CNTs exhibits excellent catalytic activity (Eonset = ~0.85 V) and the selectivity (~90%) for H2O2 production through the electrochemical reduction of oxygen. This can be attributed to the NiCo nanoalloy core and the presence of CNTs with abundant oxygen-containing functional groups (e.g., -COOH and C-O-C), as confirmed by density function theory calculations. Overall, this work presents a straightforward and green approach for valorizing and upcycling various waste LIBs and LDPE plastics.

Shining New Light on Biological Systems: Luminescent Transition Metal Complexes for Bioimaging and Biosensing Applications.

Luminescence imaging is a powerful and versatile technique for investigating cell physiology and pathology in living systems, making significant contributions to life science research and clinical diagnosis. In recent years, luminescent transition metal complexes have gained significant attention for diagnostic and therapeutic applications due to their unique photophysical and photochemical properties. In this Review, we provide a comprehensive overview of the recent development of luminescent transition metal complexes for bioimaging and biosensing applications, with a focus on transition metal centers with a d6, d8, and d10 electronic configuration. We elucidate the structure-property relationships of luminescent transition metal complexes, exploring how their structural characteristics can be manipulated to control their biological behavior such as cellular uptake, localization, biocompatibility, pharmacokinetics, and biodistribution. Furthermore, we introduce the various design strategies that leverage the interesting photophysical properties of luminescent transition metal complexes for a wide variety of biological applications, including autofluorescence-free imaging, multimodal imaging, organelle imaging, biological sensing, microenvironment monitoring, bioorthogonal labeling, bacterial imaging, and cell viability assessment. Finally, we provide insights into the challenges and perspectives of luminescent transition metal complexes for bioimaging and biosensing applications, as well as their use in disease diagnosis and treatment evaluation.

How well do we measure the impact of bowel dysfunction on health-related quality of life after rectal cancer surgery?

BACKGROUND: Rectal cancer surgery risks causing bowel dysfunction, which has an important impact on health-related quality of life. The validity of generic tools used to measure health-related quality of life after bowel dysfunction is unclear. This study aimed to determine the content validity of health-related quality-of-life measurement tools in rectal cancer. METHODS: This was a qualitative single-center study in which adult patients who underwent rectal cancer surgery with sphincter preservation from July 2017 to October 2020 were recruited. Patients were excluded if they developed local metastasis, required a permanent stoma, or had surgery <1 year since recruitment. Telephone-based semi-structured interviews were conducted. Bowel dysfunction was measured using the Low Anterior Resection Syndrome score. Content analysis was achieved using the International Classification of Functioning framework. RESULTS: Recurrent bowel dysfunction-related concepts included "Mental functions," "Defecation functions," "Emotional functions," "Recreation and leisure," "Intimate relationships," and "Remunerative employment." A mean of 7.5 recurrent bowel dysfunction-related concepts were identified within the health-related quality of life instruments analyzed. The European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30 (n = 11) and the 36-Item Short Form Health Survey (n = 9) covered the greatest number of recurrent bowel dysfunction-related concepts. Concepts such as "Mental functions," "Urination functions," "Sexual functions," "Driving," and "Mobility" were not covered by any instrument. CONCLUSION: The content of traditional health-related quality-of-life instruments is missing important areas that represent the impact of bowel dysfunction after rectal cancer surgery on health-related quality of life. These findings could help improve patient-centered care in rectal cancer surgery.

Aetiology and epidemiology of surgical vitreoretinal presentations in an Australian paediatric population: A seven-year retrospective study.

BACKGROUND: Paediatric vitreoretinal pathology is distinct from adult cases in both presentation and surgical planning. Here we aim to report the aetiology and epidemiology in children 0-18 years requiring vitreoretinal surgery at a major tertiary paediatric hospital in Queensland, Australia. METHODS: Retrospective review of cases requiring vitreoretinal surgery between May 2015 and October 2022 was conducted. Demographics, ocular and medical history, surgical pathology, procedures performed, and epidemiology data were retrieved. Patients were grouped into three main aetiologies: traumatic, syndromic, or secondary. RESULTS: A total of 124 patients, the majority male (87, 70.2%) with a mean age of 10.3 years underwent vitreoretinal surgery. Trauma accounted for 32.3% of cases requiring surgery of which 47% were due to a penetrating eye injury. 35.5% were associated with a syndromic cause with common aetiology including coats, congenital cataract, sticklers, and retinopathy of prematurity. 32.3% developed secondary pathology and retinal detachment was the primary cause for surgery (55%). The average time from symptom onset to presentation was 30 days (SD 56.88) with patients living an average of 306.2 km (SD 558.9) away from the Queensland Children's Hospital. Older age was significantly associated with increased days to presentation in the traumatic group (p < 0.05). CONCLUSIONS: This study provides an insight into the aetiology and epidemiology of paediatric vitreoretinal presentations in Queensland, Australia.

Construction of photofunctional peptide conjugates through selective modification of N-terminal cysteine with cyclometallated iridium(III) 2-formylphenylboronic acid complexes for organelle-specific imaging, enzyme activity sensing and photodynamic therapy.

Luminescent cyclometallated iridium(III) complexes bearing a 2-formylphenylboronic acid moiety were designed; one of the complexes was utilised to modify peptides containing an N-terminal cysteine to afford luminescent conjugates with selective organelle-targeting or furin-responsive properties.

Donor Age More Than 20 Years Greater Than Recipient Age Is Associated With Worse 5-Year Survival in Young Adult Heart Transplantation.

Prior studies indicate donor age-recipient age (DA-RA) difference may be of prognostic value in adolescents, although not adults. We aim to analyze the relationship between DA-RA difference and long-term survival of young adult heart transplantation (HTx) recipients. First-time, single-organ HTx recipients aged 18-30 who underwent HTx between 2010 and 2020 were analyzed from the United Network for Organ Sharing (UNOS) registry. Four cohorts were created based on DA-RA difference. The primary outcome was 5 year post-HTx survival. Secondary outcome was post-HTx complications. One thousand eight hundred three donor-recipient pairs were divided into four groups: DA-RA < 0, 0 ≤ DA-RA < 10, 10 ≤ DA-RA < 20, and DA-RA ≥ 20 with 682 (37.8%), 651 (36.1%), 356 (19.7%), 114 (6.3%) pairs in each cohort, respectively. The estimated 5 year survival of the DA-RA ≥ 20 cohort was 66.5% compared to the other three groups at ~75%. After adjustment, DA-RA ≥ 20 was independently associated with worse survival compared to DA-RA < 0 (adjusted hazard ratio [HR] = 1.55; 95% confidence interval [CI] = 1.06-2.27; log-rank p = 0.008). There was no significant difference in complication incidence across cohorts. Among young adults, accepting a donor heart more than 20 years older than the recipient was associated with worse 5 year survival. We did not detect a significant difference up to 20 years. This information may help guide appropriate donor selection in the young adult population.

Optimized Transition Metal Phosphides for Direct Seawater Electrolysis: Current Trends.

Seawater electrolysis presents a viable route for sustainable large-scale hydrogen production, yet its practical application is hindered by several technical challenges. These include the sluggish kinetics of hydrogen evolution, poor stability, cation deposition at the cathode, electrode corrosion, and competing chloride oxidation at the anode. To overcome these obstacles, the development of innovative electrocatalysts is crucial. Transition metal phosphides (TMPs) have emerged as promising candidates owing to their superior catalytic performance and tunable structural properties. This review provides a comprehensive analysis of recent progress in the structural engineering of TMPs tailored for efficient seawater electrolysis. We delve into the catalytic mechanisms underpinning hydrogen and oxygen evolution reactions in different pH conditions, along with the detrimental side reactions that impede hydrogen production efficiency. Several methods to prepare TMPs are then introduced. Additionally, detailed discussions on structural modifications and interface engineering tactics are presented, showcasing strategies to enhance the activity and durability of TMP electrocatalysts. By analyzing current research findings, our review aims to inform ongoing research endeavors and foster advancements in seawater electrolysis for practical and ecologically sound hydrogen generation.

Spatial engineering of single-atom Fe adjacent to Cu-assisted nanozymes for biomimetic O2 activation.

The precise design of single-atom nanozymes (SAzymes) and understanding of their biocatalytic mechanisms hold great promise for developing ideal bio-enzyme substitutes. While considerable efforts have been directed towards mimicking partial bio-inspired structures, the integration of heterogeneous SAzymes configurations and homogeneous enzyme-like mechanism remains an enormous challenge. Here, we show a spatial engineering strategy to fabricate dual-sites SAzymes with atomic Fe active center and adjacent Cu sites. Compared to planar Fe-Cu dual-atomic sites, vertically stacked Fe-Cu geometry in FePc@2D-Cu-N-C possesses highly optimized scaffolds, favorable substrate affinity, and fast electron transfer. These characteristics of FePc@2D-Cu-N-C SAzyme induces biomimetic O2 activation through homogenous enzymatic pathway, resembling functional and mechanistic similarity to natural cytochrome c oxidase. Furthermore, it presents an appealing alternative of cytochrome P450 3A4 for drug metabolism and drug-drug interaction. These findings are expected to deepen the fundamental understanding of atomic-level design in next-generation bio-inspired nanozymes.

Mitochondria-targeting biocompatible fluorescent BODIPY probes.

An increase in the mitochondrial membrane potential (MMP) is a characteristic feature of cancer and cardiovascular disease. Therefore, it remains of crucial importance to develop new and improved fluorescent probes that are sensitive to the MMP, to report on mitochondrial health and function. Reported here are the design, synthesis, photophysical properties and biological characterisation of a series of BODIPY dyes, BODIPY-Mito-n, for mitochondria-targeted fluorescence imaging applications. Six BODIPY-Mito-n analogues were synthesised under mild conditions, and displayed excellent fluorescence quantum yields of between 0.59 and 0.72 in aqueous environments at physiological pH (pH = 7.4). The incorporation of poly(ethylene glycol) (PEG) chains to the triarylphosphonium cation moiety significantly improved the biocompatibility of the probes (BODIPY-Mito-6, IC50 > 50 µM). All BODIPY-Mito-n compounds demonstrated a high MMP-sensitive localisation in the mitochondria, with Pearson's correlation coefficients (PCC) of between 0.76 and 0.96. Compounds BODIPY-Mito-2 and BODIPY-Mito-6 revealed the highest sensitivity to the MMP, with a decrease in the emission intensity of 62% and 75%, respectively following MMP depolarisation. It is anticipated that the highest MMP sensitivity and enhanced biocompatibility of BODIPY-Mito-6 could lead to the development of new probes for mitochondrial imaging in the future.