Incidence and risk factors of breast cancer-related lymphedema in Korea: A nationwide retrospective cohort study.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a secondary lymphedema that occurs after breast cancer related treatments. BCRL develops from damage or dysfunction of the normally functioning lymphatic system due to surgery, radiation therapy and rarely due to cancer recurrence. This nationwide, retrospective study was aimed at investigating the incidence and risk factors of BCRL using the database of the Korean National Health Insurance Service (NHIS). METHODS: Patients with newly diagnosed breast cancer who underwent breast surgery from January 1, 2017 to December 31, 2020, were recruited. The incidence was compared by four groups according to the operation type of breast cancer (breast conserving surgery (BCS) with sentinel lymph node biopsy (S), BCS with axillary lymph node dissection (A), total mastectomy (TM) with S, modified radical mastectomy(MRM)). The incidence rates of lymphedema were calculated by the number of incident events by the total follow-up period. Cox proportional hazard regression was used to calculate the risk of incidence of lymphedema based on a patients' characteristics, breast cancer treatment and comorbidities. RESULTS: The final cohort of operation subjects that satisfied the inclusion criteria was 34,676. BCRL occurred in 4,242 patients (12.2%), and the median follow-up period was 695.4 days. The BCRL was diagnosed in the BCS with S (8.0%), BCS with A (23.5%), TM with S (10.7%), MRM (28.5%) with an incidence of 40.8, 132.2, 55.8 and 171.8 per 1,000 person-years, respectively. Young age, obesity, chemotherapy, radiotherapy, residence in metropolitan areas and hyperlipidemia were identified as risk factors. CONCLUSION: In Korea, the incidence of BCRL was found to be 12.2%, with the highest risk observed among patients who underwent MRM. Therefore, surgical oncologists should meticulously assess the appropriate surgical approach and consider providing education to patients with risk factors for BCRL, aiming to ensure effective prevention strategies.

Deep learning algorithm for the automated detection and classification of nasal cavity mass in nasal endoscopic images.

Nasal endoscopy is routinely performed to distinguish the pathological types of masses. There is a lack of studies on deep learning algorithms for discriminating a wide range of endoscopic nasal cavity mass lesions. Therefore, we aimed to develop an endoscopic-examination-based deep learning model to detect and classify nasal cavity mass lesions, including nasal polyps (NPs), benign tumors, and malignant tumors. The clinical feasibility of the model was evaluated by comparing the results to those of manual assessment. Biopsy-confirmed nasal endoscopic images were obtained from 17 hospitals in South Korea. Here, 400 images were used for the test set. The training and validation datasets consisted of 149,043 normal nasal cavity, 311,043 NP, 9,271 benign tumor, and 5,323 malignant tumor lesion images. The proposed Xception architecture achieved an overall accuracy of 0.792 with the following class accuracies on the test set: normal = 0.978 ± 0.016, NP = 0.790 ± 0.016, benign = 0.708 ± 0.100, and malignant = 0.698 ± 0.116. With an average area under the receiver operating characteristic curve (AUC) of 0.947, the AUC values and F1 score were highest in the order of normal, NP, malignant tumor, and benign tumor classes. The classification performances of the proposed model were comparable with those of manual assessment in the normal and NP classes. The proposed model outperformed manual assessment in the benign and malignant tumor classes (sensitivities of 0.708 ± 0.100 vs. 0.549 ± 0.172, 0.698 ± 0.116 vs. 0.518 ± 0.153, respectively). In urgent (malignant) versus nonurgent binary predictions, the deep learning model achieved superior diagnostic accuracy. The developed model based on endoscopic images achieved satisfactory performance in classifying four classes of nasal cavity mass lesions, namely normal, NP, benign tumor, and malignant tumor. The developed model can therefore be used to screen nasal cavity lesions accurately and rapidly.

Long-term impacts of COVID-19 on severe exacerbation and mortality in adult asthma: A nationwide population-based cohort study.

BACKGROUND: In adults with asthma, the long-term impact of previous coronavirus disease 2019 (COVID-19) on severe exacerbations and mortality is unclear. OBJECTIVE: We evaluated the long-term risk of severe exacerbation and mortality in adults with asthma who recovered from COVID-19. METHODS: Using the Korean National Health Insurance claim-based database, we compared the risk of severe exacerbations (emergency room visits or hospitalization) and mortality in adults with asthma aged >20 years recovered from COVID-19 between October 8, 2020, and December 16, 2021 (COVID-19 cohort, n=10,739) with 1:1 propensity score-matched controls (n=10,739). RESULTS: During a median follow-up of 87 (range, 15-448) days, the incidence rate of severe exacerbation in the COVID-19 cohort and matched cohort was 187.3 and 119.3 per 10,000 person-years, respectively. The COVID-19 cohort had a higher risk of severe exacerbation compared to the matched cohort (hazard ratio=1.57; 95% confidence interval [CI]=1.06-2.32). During a median follow-up of 360 (range, 15-721) days, the incidence rate of death in the COVID-19 and matched cohort was 128.3 and 73.5 per 10,000 person-years, respectively. The COVID-19 cohort had a higher risk of death (hazard ratio=1.76; 95% CI=1.33-2.30) compared to the matched cohort. When further analyzed by COVID-19 severity, severe COVID-19 was associated with a 5.12-fold (95% CI=3.27-8.01) and 7.31-fold (95% CI=5.41-9.88) increased risk of severe exacerbation and death, respectively, but non-severe COVID-19 was not. CONCLUSION: Our study heightens that severe COVID-19 is associated with increased long-term risk of severe exacerbation and mortality among individuals with asthma.

Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle.

Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects in deep-seated tumors remains challenging. Herein, we introduce a novel self-assembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λem = 1105 nm), as a first example of a Ru(II) supramolecular ICD inducer. Ru1105 synergistically potentiates immunomodulatory responses and reduces adverse effects in deep-seated tumors through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting of tumor cells, precision organelle localization, and improved tumor penetration/retention capabilities. Specifically, Ru1105 demonstrates excellent depth-activated ROS production (∼1 cm), strong resistance to diffusion, and anti-ROS quenching. Moreover, Ru1105 exhibits promising results in cellular uptake and ROS generation in cancer cells and multicellular tumor spheroids. Importantly, Ru1105 induces more efficient ICD in an ultralow dose (10 µM) compared to the conventional anticancer agent, oxaliplatin (300 µM). In vivo experiments further confirm Ru1105's potency as an ICD inducer, eliciting CD8+ T cell responses and depleting Foxp3+ T cells with minimal adverse effects. Our research lays the foundation for the design of secure and exceptionally potent metal-based ICD agents in immunotherapy.

Recent advances in the fabrication of organic solvent nanofiltration membranes using covalent/metal organic frameworks.

Organic solvent nanofiltration (OSN) has evolved as a vital technological frontier with paramount significance in the separation and purification of organic solvents. Its implication is particularly prominent in industries such as pharmaceuticals, petrochemicals, and environmental remediation. This comprehensive review, meticulously navigates through the current state of research in OSN membranes, unveiling both the critical challenges and promising opportunities that beckon further exploration. The central focus of this review is on the unique utilization of covalent organic frameworks (COFs) and metal-organic frameworks (MOFs) in OSN membrane design, leveraging their distinctive structural attributes-tunable porosity, robust chemical stability, and molecular sieving capabilities. These qualities position them as exceptional candidates for crafting membranes tailored to the intricacies of organic solvent environments. Our investigation extends into the fundamental principles that render COFs and MOFs adept in OSN applications, dissecting their varied fabrication methods while offering insights into the advantages and limitations of each. Moreover, we address environmental and sustainability considerations in the use of COF and MOF-based OSN membranes. Furthermore, we meticulously present the latest advancements and innovations in this burgeoning field, charting a course toward potential future directions and emerging research areas. By underscoring the challenges awaiting exploration, this review not only provides a panoramic view of the current OSN landscape but also lays the groundwork for the evolution of efficient and sustainable OSN technologies, specifically harnessing the unique attributes of COFs and MOFs.

Lutetium texaphyrin: A photocatalyst that triggers pyroptosis via biomolecular photoredox catalysis.

Photon-controlled pyroptosis activation (PhotoPyro) is a promising technique for cancer immunotherapy due to its noninvasive nature, precise control, and ease of operation. Here, we report that biomolecular photoredox catalysis in cells might be an important mechanism underlying PhotoPyro. Our findings reveal that the photocatalyst lutetium texaphyrin (MLu) facilitates rapid and direct photoredox oxidation of nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate, and various amino acids, thereby triggering pyroptosis through the caspase 3/GSDME pathway. This mechanism is distinct from the well-established role of MLu as a photodynamic therapy sensitizer in cells. Two analogs of MLu, bearing different coordinated central metal cations, were also explored as controls. The first control, gadolinium texaphyrin (MGd), is a weak photocatalyst but generates reactive oxygen species (ROS) efficiently. The second control, manganese texaphyrin (MMn), is ineffective as both a photocatalyst and a ROS generator. Neither MGd nor MMn was found to trigger pyroptosis under the conditions where MLu was active. Even in the presence of a ROS scavenger, treating MDA-MB-231 cells with MLu at concentrations as low as 50 nM still allows for pyroptosis photo-activation. The present findings highlight how biomolecular photoredox catalysis could contribute to pyroptosis activation by mechanisms largely independent of ROS.

Early onset diagnosis in Alzheimer's disease patients via amyloid-ß oligomers-sensing probe in cerebrospinal fluid.

Amyloid-ß (Aß) oligomers are implicated in the onset of Alzheimer's disease (AD). Herein, quinoline-derived half-curcumin-dioxaborine (Q-OB) fluorescent probe was designed for detecting Aß oligomers by finely tailoring the hydrophobicity of the biannulate donor motifs in donor-π-acceptor structure. Q-OB shows a great sensing potency in dynamically monitoring oligomerization of Aß during amyloid fibrillogenesis in vitro. In addition, we applied this strategy to fluorometrically analyze Aß self-assembly kinetics in the cerebrospinal fluids (CSF) of AD patients. The fluorescence intensity of Q-OB in AD patients' CSF revealed a marked change of log (I/I0) value of 0.34 ± 0.13 (cognitive normal), 0.15 ± 0.12 (mild cognitive impairment), and 0.14 ± 0.10 (AD dementia), guiding to distinguish a state of AD continuum for early diagnosis of AD. These studies demonstrate the potential of our approach can expand the currently available preclinical diagnostic platform for the early stages of AD, aiding in the disruption of pathological progression and the development of appropriate treatment strategies.

Theranostic Fluorescent Probes.

The ability to gain spatiotemporal information, and in some cases achieve spatiotemporal control, in the context of drug delivery makes theranostic fluorescent probes an attractive and intensely investigated research topic. This interest is reflected in the steep rise in publications on the topic that have appeared over the past decade. Theranostic fluorescent probes, in their various incarnations, generally comprise a fluorophore linked to a masked drug, in which the drug is released as the result of certain stimuli, with both intrinsic and extrinsic stimuli being reported. This release is then signaled by the emergence of a fluorescent signal. Importantly, the use of appropriate fluorophores has enabled not only this emerging fluorescence as a spatiotemporal marker for drug delivery but also has provided modalities useful in photodynamic, photothermal, and sonodynamic therapeutic applications. In this review we highlight recent work on theranostic fluorescent probes with a particular focus on probes that are activated in tumor microenvironments. We also summarize efforts to develop probes for other applications, such as neurodegenerative diseases and antibacterials. This review celebrates the diversity of designs reported to date, from discrete small-molecule systems to nanomaterials. Our aim is to provide insights into the potential clinical impact of this still-emerging research direction.

Breaking Iron Homeostasis: Iron Capturing Nanocomposites for Combating Bacterial Biofilm.

Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal-organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them. Owing to the similarity between iron/hemin and gallium/TCPP, gallium-incorporated porphyrin potentially deceives bacteria into uptaking gallium ions and concurrently extracts iron ions from the surrounding bacteria milieu through the porphyrin ring. This strategy orchestrates a "give and take" approach for Ga3+/Fe3+ exchange. Simultaneously, polymer dots can impede bacterial iron metabolism and serve as real-time fluorescent iron-sensing probes to continuously monitor dynamic iron restriction status. INIT based on Ga-CT@P nanocomposites induced long-term iron starvation, which affected iron-sulfur cluster biogenesis and carbohydrate metabolism, ultimately facilitating biofilm eradication and tissue regeneration. Therefore, this study presents an innovative antibacterial strategy from a nutritional perspective that sheds light on refractory bacterial infection treatment and its future clinical application.

Increasing incidence of Parkinson's disease in patients with epilepsy: A Nationwide cohort study.

BACKGROUND: Although epilepsy is an uncommon comorbidity of Parkinson's disease (PD), the exact incidence of PD among the patients with epilepsy is not clarified yet. OBJECTIVES: We aimed to estimate the incidence of PD in patients with epilepsy and explore the association between epilepsy and PD. METHODS: Epilepsy patients enrolled in the National Health Insurance Service Health Screening Cohort (NHIS-HealS) (2002-2013) between 2003 and 2007 were set up as the experimental group. The major outcome was the occurrence of PD. Non-epilepsy patients were obtained through Propensity Score Matching of 'greedy nearest neighbor' algorithm in 1:1 ratio. The Cox Proportional Hazards model was used to calculate PD incidence and hazard ratio (HR). RESULTS: A total of 10,510 patients were finally included in the study, which contained 5255 patients in epilepsy and non-epilepsy groups, respectively. During the follow-up period, 85 patients with Parkinson's disease among 5255 patients with epilepsy and 57 patients with Parkinson's disease among 5255 patients without epilepsy occurred. The 10,000 Person-Year (PY), representing the number of PD patients per 10,000 per year, was 21.38 in the epilepsy group and 11.18 in the non-epilepsy group. When all variables were adjusted, it was found that the epilepsy group had a 2.19 times significantly higher risk of developing Parkinson's disease than the control group (The adjusted HR: 2.19 (95% CI, 1.55-3.12)). CONCLUSION: This study indicates an increased risk of PD in patients with epilepsy. However, further research is needed to prove an exact causal relationship between these two brain disorders.

Photonic control of ligand nanospacing in self-assembly regulates stem cell fate.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Risk of Alopecia Areata After COVID-19.

This cohort study examines the incidence, prevalence, and risk of alopecia areata after COVID-19.

Discovery of thiophen-2-ylmethylene bis-dimedone derivatives as novel WRN inhibitors for treating cancers with microsatellite instability.

Microsatellite instability (MSI) is a hypermutable condition caused by DNA mismatch repair system defects, contributing to the development of various cancer types. Recent research has identified Werner syndrome ATP-dependent helicase (WRN) as a promising synthetic lethal target for MSI cancers. Herein, we report the first discovery of thiophen-2-ylmethylene bis-dimedone derivatives as novel WRN inhibitors for MSI cancer therapy. Initial computational analysis and biological evaluation identified a new scaffold for a WRN inhibitor. Subsequent SAR study led to the discovery of a highly potent WRN inhibitor. Furthermore, we demonstrated that the optimal compound induced DNA damage and apoptotic cell death in MSI cancer cells by inhibiting WRN. This study provides a new pharmacophore for WRN inhibitors, emphasizing their therapeutic potential for MSI cancers.

Increased Risk of New-Onset Asthma After COVID-19: A Nationwide Population-Based Cohort Study.

BACKGROUND: Previous studies have suggested that respiratory virus infections may be associated with new-onset asthma. However, whether coronavirus disease 2019 (COVID-19) is associated with an increased risk of new-onset asthma remains unclear. OBJECTIVE: We aimed to evaluate whether recent COVID-19 increases the risk of new-onset asthma and whether COVID-19 vaccination could mitigate this risk. METHODS: We constructed 3 different study designs using the Korean National Health Insurance claim-based database: study 1: COVID-19-diagnosed subjects (COVID-19 cohort) and their matched controls; study 2: COVID-19-vaccinated subjects (vaccination cohort) and their matched controls; and study 3: vaccination cohort and their matched controls, excluding subjects diagnosed with COVID-19. RESULTS: In study 1, 1.6% of the COVID-19 cohort and 0.7% of the matched cohort developed new-onset asthma, with incidences of 31.28 and 14.55 per 1,000 person-years, respectively (P < .001). The COVID-19 cohort had a higher risk of new-onset asthma (adjusted hazard ratio [aHR] 2.14; 95% CI 1.88-2.45) than matched controls. In study 2, the vaccination cohort had a lower risk of new-onset asthma than the matched controls (aHR 0.82; 95% CI 0.76-0.89). However, among subjects without a COVID-19 diagnosis, COVID-19 vaccination was not associated with a reduced risk of new-onset asthma in study 3 (aHR 0.95; 95% CI 0.87-1.04). In subgroup analysis, the risk of new-onset asthma was significantly lower in fully vaccinated subjects and higher in older subjects and in those with diabetes mellitus than in their counterparts. CONCLUSIONS: The COVID-19 was associated with a higher incidence of new-onset asthma, which might be preventable by COVID-19 vaccination.

Endogenous CO imaging in bacterial pneumonia with a NIR fluorescent probe.

Bacterial pneumonia is a serious respiratory illness that poses a great threat to human life. Rapid and precise diagnosis of bacterial pneumonia is crucial for symptomatic clinical treatment. Endogenous carbon monoxide (CO) is regarded as a significant indicator of bacterial pneumonia; herein, we developed a near-infrared (NIR) probe for fluorescence and photoacoustic (PA) dual-mode imaging of endogenous CO in bacterial pneumonia. NO2-BODIPY could rapidly and specifically react with CO to produce strong NIR fluorescence as well as ratiometric PA signals. NO2-BODIPY has outstanding features including fast response, fluorescence/PA dual mode signals, good specificity, and a low limit of detection (LOD = 20.3 nM), which enables it to image endogenous CO in cells and bacterial pneumonia mice with high sensitivity and high contrast ratio. In particular, NO2-BODIPY has two-photon excited (1340 nm, σ1 = 1671 GM) NIR fluorescence and has been utilized to image endogenous CO in bacterial pneumonia mice with deep tissue penetration. NO2-BODIPY has been demonstrated a good capability of fluorescence/PA dual-mode imaging of CO in bacterial pneumonia mice, providing a precise manner to diagnose bacterial pneumonia.

Real-Time Live Imaging of Osteoclast Activation via Cathepsin K Activity in Bone Diseases.

Intravital fluorescence imaging of functional osteoclasts within their intact disease context provides valuable insights into the intricate biology at the microscopic level, facilitating the development of therapeutic approaches for osteoclast-associated bone diseases. However, there is a lack of studies investigating osteoclast activity within deep-seated bone lesions using appropriate fluorescent probes, despite the advantages offered by the multi-photon excitation system in enhancing deep tissue imaging resolution. In this study, we report on the intravital tracking of osteoclast activity in three distinct murine bone disease models. We utilized a cathepsin K (CatK)-responsive two-photon fluorogenic probe (CatKP1), which exhibited a notable fluorescence turn-on response in the presence of active CatK. By utilizing CatKP1, we successfully monitored a significant increase in osteoclast activity in hindlimb long bones and its attenuation through pharmacological intervention without sacrificing mice. Thus, our findings highlight the efficacy of CatKP1 as a valuable tool for unraveling pathological osteoclast behavior and exploring novel therapeutic strategies.

Risk of Ischemic Heart Disease in Chronic Obstructive Pulmonary Disease: A Nationwide Cohort Study.

BACKGROUND: Subjects with chronic obstructive pulmonary disease (COPD) have a higher risk of ischemic heart disease (IHD) than individuals without COPD; however, longitudinal evidence is lacking. Therefore, we aimed to estimate the risk of IHD between COPD and control cohorts using a longitudinal nationwide database. METHODS: We used 2009-2017 data from the Korean National Health Insurance Service National Sample Cohort (NHIS-NSC). Adult participants at least 20 years of age who underwent health examinations and without a history of COPD or IHD were included (n = 540,976). Participants were followed from January 1, 2009, until death, development of IHD, or December 31, 2019, whichever came first. RESULTS: At baseline, there were 3,421 participants with incident COPD and 537,555 participants without COPD. During a median of 8.0 years (5.3-9.1 years) of follow-up, 2.51% of the participants with COPD (n = 86) and 0.77% of the participants without COPD (n = 4,128) developed IHD, with an incidence of 52.24 and 10.91 per 10,000 person-years, respectively. Participants with COPD had a higher risk of IHD (adjusted hazard ratio, 1.55; 95% confidence interval, 1.25-1.93) than subjects without COPD. Demographics such as age, sex, body mass index, and personal health behaviors including smoking status and physical activity did not show significant interaction with the relationship between COPD and IHD (P for interaction > 0.05 for all). CONCLUSION: The results indicate that COPD is associated with the development of IHD independent of demographic characteristics and health-related behaviors. Based on these results, clinicians should closely monitor the onset of IHD in subjects with COPD.

Metal Modulation: An Effortless Tactic for Refining Photoredox Catalysis in Living Cells.

The remarkable impact of photoredox catalytic chemistries has sparked a wave of innovation, opening doors to novel biotechnologies in the realm of catalytic antitumor therapy. Yet, the quest for novel photoredox catalysts (PCs) suitable for living systems, or the enhancement of catalytic efficacy in existing biocompatible PC systems, persists as a formidable challenge. Within this context, we introduce a readily applicable metal modulation strategy that significantly augments photoredox catalysis within living cells, exemplified by a set of metalloporphyrin complexes termed M-TCPPs (M = Zn, Mn, Ni, Co, Cu). Among these complexes, Zn-TCPP emerges as an exceptional catalyst, displaying remarkable photocatalytic activity in the oxidation of nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate (NADPH), and specific amino acids. Notably, comprehensive investigations reveal that Zn-TCPP's superior catalytic prowess primarily arises from the establishment of an efficient oxidative cycle for PC, in contrast to previously reported PCs engaged in reductive cycles. Moreover, theoretical calculations illuminate that amplified intersystem crossing rates and geometry alterations in Zn-TCPP contribute to its heightened photocatalytic performance. In vitro studies demonstrated that Zn-TCPP exhibits therapeutic potential and is found to be effective for photocatalytic antitumor therapy in both glioblastoma G98T cells and 3D multicellular spheroids. This study underscores the transformative role of "metal modulation" in advancing high-performance PCs for catalytic antitumor therapy, marking a significant stride toward the realization of this innovative therapeutic approach.