Impact of resistance exercise on patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) has become an increasingly important public health disease with a high incidence rate and mortality. Although several studies have explored the effectiveness of resistance exercise in improving the prognosis of CKD patients, the number of studies is still limited and the results are still controversial. OBJECTIVES: We conducted this meta-analysis of randomized controlled trials (RCT) studies to evaluate the effectiveness of resistance exercise on CKD patients. METHODS: The PubMed, Embase, and Cochrane Library databases were searched from the inception date to October 2023. The meta-analysis was conducted to evaluate 12 main indicators, including glomerular filtration rate (GFR)(ml/(min•1.73m2)), C-reactive protein (CRP) (mg/L), serum creatinine (mg/dL), hemoglobin (g/dL), Glycosylated Hemoglobin, Type A1C (HBA1c) (%), high Density Lipoprotein (HDL) (mg/dL), low Density Lipoprotein (LDL) (mg/dL), 6-min walk(m), body mass index (BMI) (kg/m2), fat-free mass (kg), fat mass (kg), grip strength (kgf). RESULTS: Sixteen RCT studies were included in this meta-analysis from 875 records. GFR exhibited no significant change in CKD patients treated with resistance exercise (WMD 1.82; 95%CI -0.59 to 4.23; P = 0.139). However, 6-min walk (WMD 89.93; 95%CI 50.12 to 129.74; P = 0.000), fat-free mass (WMD 6.53; 95%CI 1.14 to 11.93; P = 0.018) and grip strength (WMD 3.97; 95%CI 1.89 to 6.05; P = 0.000) were significantly improved with resistance exercise. The level of CRP (WMD - 2.46; 95%CI -4.21 to -0.72; P = 0.006) and HBA1c (WMD - 0.46; 95%CI -0.63 to -0.29; P = 0.000) dropped significantly after resistance exercise treatment. CONCLUSIONS: Resistance exercise can improve physical function, metabolic condition, inflammatory response and cardiopulmonary function in CKD patients, specifically reflected in the increase of indicators fat-free mass, grip strength, 6-min walk, as well as the decrease of indicators HBA1c and CRP.

A before-after study to evaluate the effect of pharmacy workflow redesign to improve pharmacy waiting time and reduce medication near misses in Malaysia.

OBJECTIVES: This study aimed to evaluate the effectiveness of workflow redesign (eaST system) on pharmacy waiting time and near-missed events. We also investigated other factors that may potentially affect these study outcomes. METHODS: A quasi-experimental (before-after) study design was adopted. Pre-intervention data were collected over 7 months (January-July 2017). Subsequently, the workflow redesign (eaST system) was implemented and the effect of the intervention (August 2017-February 2018) was evaluated. Univariate analysis was used to compare the differences between pre-intervention and post-intervention of pharmacy waiting time and near-missed events. Significant factors affecting study outcomes were analysed using linear regression analysis. KEY FINDINGS: A total of 210,530 prescriptions were analysed. The eaST system significantly increases the percentage of prescriptions dispensed within 30 min per day (median = 68 (interquartile range (IQR) = 41) vs. median = 93 (IQR = 33), P < 0.001) and reduced the mean percentage of near-missed events (mean = 50.71 (standard deviation (SD) = 23.95) vs. mean = 27.87 (SD = 12.23), P < 0.001). However, the eaST system's effects on related outcomes were conditional on a three-way interaction effect. The eaST system's effects on pharmacy waiting time were influenced by the number of prescriptions received and the number of PhIS server disruptions. Conversely, the eaST system's effects on near-missed events were influenced by the number of pharmacy personnel and number of controlled medications. CONCLUSIONS: Overall, the eaST system improved the pharmacy waiting time and reduced near-missed events.

Limitations to sustainable renewable jet fuels production attributed to cost than energy-water-food resource availability.

Renewable jet fuel (RJF) is often touted as the only viable sustainable energy source for the aviation sector, given the difficulties faced by other low-carbon energy sources in overcoming technological barriers. Despite that, the sustainability of RJF is still in dispute due to the conflicting requirements in natural resource for producing the fuels. We introduce a holistic 25-indicator sustainability index encompassing the four domains of energy-water-food nexus and governance, that measures the potential impact of RJF production on 154 countries (and territories) through the oil-to-jet, alcohol-to-jet and gas-to-jet conversion methods. Countries and territories are ranked according to the composite index scores of the four domains. The sustainability index model provides insights on how RJF affords the aviation sector a clean slate in determining the manner of development in a sustainably and equitable way, while also marching towards the long-term goal of carbon neutrality, in alignment with the Sustainable Development Goals.

Synthesis of two-dimensional triazine covalent organic frameworks at ambient conditions to detect and remove water pollutants.

Synthesis of fully triazine frameworks (C3N3) by metal catalyzed reactions at high temperatures results in carbonized and less-defined structures. Moreover, metal impurities affect the physicochemical, optical and electrical properties of the synthesized frameworks, dramatically. In this work, two-dimensional C3N3 (2DC3N3) has been synthesized by in situ catalyst-free copolymerization of sodium cyanide and cyanuric chloride, as cheap and commercially available precursors, at ambient conditions on gram scale. Reaction between sodium cyanide and cyanuric chloride resulted in electron-poor polyfunctional intermediates, which converted to 2DC3N3 with several hundred micrometers lateral size at ambient conditions upon [2 + 2+2] cyclotrimerization. 2DC3N3 sheets, in bulk and individually, showed strong fluorescence with 63% quantum yield and sensitive to small objects such as dyes and metal ions. The sensitivity of 2DC3N3 emission to foreign objects was used to detect low concentration of water impurities. Due to the high negative surface charge (-37.7 mV) and dispersion in aqueous solutions, they demonstrated a high potential to remove positively charged dyes from water, exemplified by excellent removal efficiency (>99%) for methylene blue. Taking advantage of the straightforward production and strong interactions with dyes and metal ions, 2DC3N3 was integrated in filters and used for the fast detection and efficient removal of water impurities.

Effects of mobile apps intervention on medication adherence and type 2 diabetes mellitus control: A systematic review and meta-analysis.

INTRODUCTION: The prevalence of non-adherence to antidiabetic treatment remains high despite various efforts. Thus, the positive effects of the antidiabetic treatment cannot be optimised and the disease progresses to complications. This present systematic review and meta-analysis aimed to evaluate the effects of mobile applications (apps) intervention on medication adherence and type 2 diabetes mellitus (T2DM) control. METHODS: This research was conducted following the PRISMA guidelines. The databases that had been searched included Web of Science, PubMed, Scopus, Cochrane Library and Ovid from 2017 to 2022. Study characteristics were retrieved and study outcomes such as adherence status and diabetes control were extracted and quantitatively analysed through meta-analysis. RESULTS: Eight studies met the final inclusion criteria and were included in the analysis, contributing to a total of 884 subjects. The methodological quality of the included studies was variable. Three studies reported statistically significant improvement in medication adherence through mobile apps intervention. Additionally, the mobile apps intervention proved effective in reducing glycaemic outcomes. As compared to non-mobile apps users, glycated haemoglobin (HbA1c) significantly decreased by 0.36% (95% CI -0.47% to -0.25%), whereas fasting plasma glucose (FPG) significantly decreased by 16.75 mg/dL (95% CI -17.60 mg/dL to -15.80 mg/dL). CONCLUSION: Mobile apps intervention had beneficial impacts on medication adherence and glycaemic parameters. Future research should explore the best practical approach for real-world settings.

Post COVID-19 ENERGY sustainability and carbon emissions neutrality.

This review covers the recent advancements in selected emerging energy sectors, emphasising carbon emission neutrality and energy sustainability in the post-COVID-19 era. It benefited from the latest development reported in the Virtual Special Issue of ENERGY dedicated to the 6th International Conference on Low Carbon Asia and Beyond (ICLCA'20) and the 4th Sustainable Process Integration Laboratory Scientific Conference (SPIL'20). As nations bind together to tackle global climate change, one of the urgent needs is the energy sector's transition from fossil-fuel reliant to a more sustainable carbon-free solution. Recent progress shows that advancement in energy efficiency modelling of components and energy systems has greatly facilitated the development of more complex and efficient energy systems. The scope of energy system modelling can be based on temporal, spatial and technical resolutions. The emergence of novel materials such as MXene, metal-organic framework and flexible phase change materials have shown promising energy conversion efficiency. The integration of the internet of things (IoT) with an energy storage system and renewable energy supplies has led to the development of a smart energy system that effectively connects the power producer and end-users, thereby allowing more efficient management of energy flow and consumption. The future smart energy system has been redefined to include all energy sectors via a cross-sectoral integration approach, paving the way for the greater utilization of renewable energy. This review highlights that energy system efficiency and sustainability can be improved via innovations in smart energy systems, novel energy materials and low carbon technologies. Their impacts on the environment, resource availability and social well-being need to be holistically considered and supported by diverse solutions, in alignment with the sustainable development goal of Affordable and Clean Energy (SDG 7) and other related SDGs (1, 8, 9, 11,13,15 and 17), as put forth by the United Nations.

Switching Heavy Chain Constant Domains Denatures the Paratope 3D Architecture of Influenza Monoclonal Antibodies.

Several human monoclonal Abs for treating Influenza have been evaluated in clinical trials with limited success despite demonstrating superiority in preclinical animal models including mice. To conduct efficacy studies in mice, human monoclonal Abs are genetically engineered to contain mouse heavy chain constant domain to facilitate the engagement of Fc-receptors on mouse immune effector cells. Although studies have consistently reported discrepancies in Ab effectiveness following genetic engineering, the structural and mechanistic basis for these inconsistencies remain uncharacterized. Here, we use homology modeling to predict variable region (VR) analogous monoclonal Abs possessing human IgG1, mouse IgG1, and mouse IgG2a heavy chain constant domains. We then examine predicted 3D structures for variations in the spatial location and orientation of corresponding paratope amino acid residues. By structurally aligning crystal structures of Fabs in complex with hemagglutinin (HA), we show that corresponding paratope amino acid residues for VR-analogous human IgG1, mouse IgG1, and mouse IgG2a monoclonal Abs interact differentially with HA suggesting that their epitopes might not be identical. To demonstrate that variations in the paratope 3D fine architecture have implications for Ab specificity and effectiveness, we genetically engineered VR-analogous human IgG1, human IgG4, mouse IgG1, and mouse IgG2a monoclonal Abs and explored their specificity and effectiveness in protecting MDCK cells from infection by pandemic H1N1 and H3N2 Influenza viruses. We found that VR-analogous monoclonal Abs placed on mouse heavy chain constant domains were more efficacious at protecting MDCK cells from Influenza virus infection relative to those on human heavy chain constant domains. Interestingly, mouse but not human heavy chain constant domains increased target breadth in some monoclonal Abs. These data suggest that heavy chain constant domain sequences play a role in shaping Ab repertoires that go beyond class or sub-class differences in immune effector recruitment. This represents a facet of Ab biology that can potentially be exploited to improve the scope and utilization of current therapeutic or prophylactic candidates for influenza.

Co-pyrolysis of microalgae and other biomass wastes for the production of high-quality bio-oil: Progress and prospective.

Microalgae are the most prospective raw materials for the production of biofuels, pyrolysis is an effective method to convert biomass into bioenergy. However, biofuels derived from the pyrolysis of microalgae exhibit poor fuel properties due to high content of moisture and protein. Co-pyrolysis is a simple and efficient method to produce high-quality bio-oil from two or more materials. Tires, plastics, and bamboo waste are the optimal co-feedstocks based on the improvement of yield and quality of bio-oil. Moreover, adding catalysts, especially CaO and Cu/HZSM-5, can enhance the quality of bio-oil by increasing aromatics content and decreasing oxygenated and nitrogenous compounds. Consequently, this paper provides a critical review of the production of bio-oil from co-pyrolysis of microalgae with other biomass wastes. Meanwhile, the underlying mechanism of synergistic effects and the catalytic effect on co-pyrolysis are discussed. Finally, the economic viability and prospects of microalgae co-pyrolysis are summarized.

Impacts of COVID-19 pandemic on the global energy system and the shift progress to renewable energy: Opportunities, challenges, and policy implications.

Being declared a global emergency, the COVID-19 pandemic has taken many lives, threatened livelihoods and businesses around the world. The energy industry, in particular, has experienced tremendous pressure resulting from the pandemic. In response to such a challenge, the development of sustainable resources and renewable energy infrastructure has demonstrated its potential as a promising and effective strategy. To sufficiently address the effect of COVID-19 on renewable energy development strategies, short-term policy priorities should be identified, while mid-term and long-term action plans should be formulated in achieving the well-defined renewable energy targets and progress towards a more sustainable energy future. In this review, opportunities, challenges, and significant impacts of the COVID-19 pandemic on current and future sustainable energy strategies were analyzed in detail; while drawing from experiences in identifying reasonable behaviors, orientating appropriate actions, and policy implications on the sustainable energy trajectory were also mentioned. Indeed, the question is that whether the COVID-19 pandemic will kill us or provide us with a precious lesson on future sustainable energy development.

Acid-based lignocellulosic biomass biorefinery for bioenergy production: Advantages, application constraints, and perspectives.

The production of chemicals and fuels from renewable biomass with the primary aim of reducing carbon footprints has recently become one of the central points of interest. The use of lignocellulosic biomass for energy production is believed to meet the main criteria of maximizing the available global energy source and minimizing pollutant emissions. However, before usage in bioenergy production, lignocellulosic biomass needs to undergo several processes, among which biomass pretreatment plays an important role in the yield, productivity, and quality of the products. Acid-based pretreatment, one of the existing methods applied for lignocellulosic biomass pretreatment, has several advantages, such as short operating time and high efficiency. A thorough analysis of the characteristics of acid-based biomass pretreatment is presented in this review. The environmental concerns and future challenges involved in using acid pretreatment methods are discussed in detail to achieve clean and sustainable bioenergy production. The application of acid to biomass pretreatment is considered an effective process for biorefineries that aim to optimize the production of desired products while minimizing the by-products.

Global spectrum of population-specific common missense variation in cytochrome P450 pharmacogenes.

Next-generation sequencing technology has afforded the discovery of many novel variants that are of significance to inheritable pharmacogenomics (PGx) traits but a large proportion of them have unknown consequences. These include missense variants resulting in single amino acid substitutions in cytochrome P450 (CYP) proteins that can impair enzyme function, leading to altered drug efficacy and toxicity. While most unknown variants are rare, an overlooked minority are variants that are collectively rare but enriched in specific populations. Here, we analyzed sequence variation data in 141,456 individuals from across eight study populations in gnomAD for 38 CYP genes to identify such variants in addition to common variants. By further comparison with data from two PGx-specific databases (PharmVar and PharmGKB) and ClinVar, we identified 234 missense variants in 35 CYP genes, of which 107 were unknown to these databases. Most unknown variants (n = 83) were population-specific common variants and several (n = 7) were found in important CYP pharmacogenes (CYP2D6, CYP4F2, and CYP2C19). Overall, 29% (n = 31) of 107 unknown variants were predicted to affect CYP enzyme function although further biochemical characterization is necessary. These variants may elucidate part of the unexplained interpopulation differences observed in drug response.

Structure-based virtual screening of CYP1A1 inhibitors: towards rapid tier-one assessment of potential developmental toxicants.

Cytochrome P450 1A1 (CYP1A1) metabolizes estrogens, melatonin, and other key endogenous signaling molecules critical for embryonic/fetal development. The enzyme has increasing expression during pregnancy, and its inhibition or knockout increases embryonic/fetal lethality and/or developmental problems. Here, we present a virtual screening model for CYP1A1 inhibitors based on the orthosteric and predicted allosteric sites of the enzyme. Using 1001 reference compounds with CYP1A1 activity data, we optimized the decision thresholds of our model and classified the training compounds with 68.3% balanced accuracy (91.0% sensitivity and 45.7% specificity). We applied our final model to 11 known CYP1A1 orthosteric binders and related compounds, and found that our ranking of the known orthosteric binders generally agrees with the relative activity of CYP1A1 in metabolizing these compounds. We also applied the model to 22 new test compounds with unknown/unclear CYP1A1 inhibitory activity, and predicted 16 of them are CYP1A1 inhibitors. The CYP1A1 potency and modes of inhibition of these 22 compounds were experimentally determined. We confirmed that most predicted inhibitors, including drugs contraindicated during pregnancy (amiodarone, bicalutamide, cyproterone acetate, ketoconazole, and tamoxifen) and environmental agents suspected to be endocrine disruptors (bisphenol A, diethyl and dibutyl phthalates, and zearalenone), are indeed potent inhibitors of CYP1A1. Our results suggest that virtual screening may be used as a rapid tier-one method to screen for potential CYP1A1 inhibitors, and flag them out for further experimental evaluations.

ATF3 contributes to brucine-triggered glioma cell ferroptosis via promotion of hydrogen peroxide and iron.

Ferroptotic cell death is characterized by iron-dependent lipid peroxidation that is initiated by ferrous iron and H2O2 via Fenton reaction, in which the role of activating transcription factor 3 (ATF3) remains elusive. Brucine is a weak alkaline indole alkaloid extracted from the seeds of Strychnos nux-vomica, which has shown potent antitumor activity against various tumors, including glioma. In this study, we showed that brucine inhibited glioma cell growth in vitro and in vivo, which was paralleled by nuclear translocation of ATF3, lipid peroxidation, and increases of iron and H2O2. Furthermore, brucine-induced lipid peroxidation was inhibited or exacerbated when intracellular iron was chelated by deferoxamine (500 µM) or improved by ferric ammonium citrate (500 µM). Suppression of lipid peroxidation with lipophilic antioxidants ferrostatin-1 (50 µM) or liproxstatin-1 (30 µM) rescued brucine-induced glioma cell death. Moreover, knockdown of ATF3 prevented brucine-induced accumulation of iron and H2O2 and glioma cell death. We revealed that brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT to prevent H2O2 degradation on the other hand. H2O2 then contributed to brucine-triggered iron increase and transferrin receptor upregulation, as well as lipid peroxidation. This was further verified by treating glioma cells with exogenous H2O2 alone. Moreover, H2O2 reversely exacerbated brucine-induced ER stress. Taken together, ATF3 contributes to brucine-induced glioma cell ferroptosis via increasing H2O2 and iron.

FOXO3a protects glioma cells against temozolomide-induced DNA double strand breaks via promotion of BNIP3-mediated mitophagy.

FOXO3a (forkhead box transcription factor 3a) is involved in regulating multiple biological processes in cancer cells. BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) is a receptor accounting for priming damaged mitochondria for autophagic removal. In this study we investigated the role of FOXO3a in regulating the sensitivity of glioma cells to temozolomide (TMZ) and its relationship with BNIP3-mediated mitophagy. We showed that TMZ dosage-dependently inhibited the viability of human U87, U251, T98G, LN18 and rat C6 glioma cells with IC50 values of 135.75, 128.26, 142.65, 155.73 and 111.60 µM, respectively. In U87 and U251 cells, TMZ (200 µM) induced DNA double strand breaks (DSBs) and nuclear translocation of apoptosis inducing factor (AIF), which was accompanied by BNIP3-mediated mitophagy and FOXO3a accumulation in nucleus. TMZ treatment induced intracellular ROS accumulation in U87 and U251 cells via enhancing mitochondrial superoxide, which not only contributed to DNA DSBs and exacerbated mitochondrial dysfunction, but also upregulated FOXO3a expression. Knockdown of FOXO3a aggravated TMZ-induced DNA DSBs and mitochondrial damage, as well as glioma cell death. TMZ treatment not only upregulated BNIP3 and activated autophagy, but also triggered mitophagy by prompting BNIP3 translocation to mitochondria and reinforcing BNIP3 interaction with LC3BII. Inhibition of mitophagy by knocking down BNIP3 with SiRNA or blocking autophagy with 3MA or bafilomycin A1 exacerbated mitochondrial superoxide and intracellular ROS accumulation. Moreover, FOXO3a knockdown inhibited TMZ-induced BNIP3 upregulation and autophagy activation. In addition, we showed that treatment with TMZ (100 mg·kg-1·d-1, ip) for 12 days in C6 cell xenograft mice markedly inhibited tumor growth accompanied by inducing FOXO3a upregulation, oxidative stress and BNIP3-mediated mitophagy in tumor tissues. These results demonstrate that FOXO3a attenuates temozolomide-induced DNA double strand breaks in human glioma cells via promoting BNIP3-mediated mitophagy.

Valorisation of medical waste through pyrolysis for a cleaner environment: Progress and challenges.

The COVID-19 pandemic has exerted great shocks and challenges to the environment, society and economy. Simultaneously, an intractable issue appeared: a considerable number of hazardous medical wastes have been generated from the hospitals, clinics, and other health care facilities, constituting a serious threat to public health and environmental sustainability without proper management. Traditional disposal methods like incineration, landfill and autoclaving are unable to reduce environmental burden due to the issues such as toxic gas release, large land occupation, and unsustainability. While the application of clean and safe pyrolysis technology on the medical wastes treatment to produce high-grade bioproducts has the potential to alleviate the situation. Besides, medical wastes are excellent and ideal raw materials, which possess high hydrogen, carbon content and heating value. Consequently, pyrolysis of medical wastes can deal with wastes and generate valuable products like bio-oil and biochar. Consequently, this paper presents a critical and comprehensive review of the pyrolysis of medical wastes. It demonstrates the feasibility of pyrolysis, which mainly includes pyrolysis characteristics, product properties, related problems, the prospects and future challenges of pyrolysis of medical wastes.

Case Report: A Rare Condition of Abdominal Pain: Chemotherapy Induced Portal Vein Pneumatosis Mimicking the Bowel Necrosis.

Portal vein pneumatosis is the presence of air in the portal venous system, which is one of the classic radiologic features of bowel ischemia or necrosis. However, there are several other morbidities that can have portal vein pneumatosis as a complication. This is a case of a 44-year-old man who suffered from severe abdominal pain after chemotherapy for soft tissue sarcoma of his left hip. The physical signs, laboratory findings, as well as the portal venous pneumatosis sign of the CT scan strongly indicated the probability of bowel necrosis and subjected the treatment decision of the patient finally to laparotomy. However, nothing abnormal except a segment of swollen small intestine was detected. Caution should be kept in mind when encountering a patient with suspected bowel necrosis following chemotherapy since several chemotherapeutic agents could cause portal vein pneumatosis. Diagnostic laparoscopy might be a better option for such cases.

The COVID-19 pandemic face mask waste: A blooming threat to the marine environment.

Recently, the COVID-19 disease spread has emerged as a worldwide pandemic and cause severe threats to humanity. The World Health Organisation (WHO) releases guidelines to help the countries to reduce the spread of this virus to the public, like wearing masks, hand hygiene, social distancing, shutting down all types of public transports, etc. These conditions led to a worldwide economic fall drastically, and on the other hand, indirect environmental benefits like global air quality improvement and decreased water pollution are also pictured. Currently, use of face masks is part of a comprehensive package of the prevention and control measures that can limit the spread of COVID-19 since there is no clinically proven drugs or vaccine available for COVID-19. Mostly, face masks are made of petroleum-based non-renewable polymers that are non-biodegradable, hazardous to the environment and create health issues. This study demonstrates the extensive use of the face mask and how it affects human health and the marine ecosystem. It has become a great challenge for the government sectors to impose strict regulations for the proper disposal of the masks as medical waste by the public. Neglecting the seriousness of this issue may lead to the release of large tonnes of micro-plastics to the landfill as well as to the marine environment where mostly end-up and thereby affecting their fauna and flora population vastly. Besides, this study highlights the COVID-19 spread, its evolutionary importance, taxonomy, genomic structure, transmission to humans, prevention, and treatment.

A Novel FRET Approach Quantifies the Interaction Strength of Peroxisomal Targeting Signals and Their Receptor in Living Cells.

Measuring Förster-resonance-energy-transfer (FRET) efficiency allows the investigation of protein-protein interactions (PPI), but extracting quantitative measures of affinity necessitates highly advanced technical equipment or isolated proteins. We demonstrate the validity of a recently suggested novel approach to quantitatively analyze FRET-based experiments in living mammalian cells using standard equipment using the interaction between different type-1 peroxisomal targeting signals (PTS1) and their soluble receptor peroxin 5 (PEX5) as a model system. Large data sets were obtained by flow cytometry coupled FRET measurements of cells expressing PTS1-tagged EGFP together with mCherry fused to the PTS1-binding domain of PEX5, and were subjected to a fitting algorithm extracting a quantitative measure of the interaction strength. This measure correlates with results obtained by in vitro techniques and a two-hybrid assay, but is unaffected by the distance between the fluorophores. Moreover, we introduce a live cell competition assay based on this approach, capable of depicting dose- and affinity-dependent modulation of the PPI. Using this system, we demonstrate the relevance of a sequence element next to the core tripeptide in PTS1 motifs for the interaction strength between PTS1 and PEX5, which is supported by a structure-based computational prediction of the binding energy indicating a direct involvement of this sequence in the interaction.