Safety assessment plays a fundamental role in developing a new drug via clinical trials for ethical considerations. Due to complexity, manual review is typically conducted on the totality of data to draw safety conclusions. There are some existing quantitative methods to facilitate or tailor further medical review, with a controlled error rate and integration of clinical knowledge. In addition to those two key aspects, we emphasize the importance of relying on substantial evidence to draw robust conclusions on safety. Motivated by these three important properties, we propose a two-layer Synergy Area with FDR-controlled Evaluation (SAFE) structural framework to robustly assess the safety profile in clinical trials. In the first layer of SAFE, we investigate each clinically meaningful Synergy Area (SA) based on compelling evidence. In the next layer, the false discovery rate (FDR) is controlled for potential findings across all SAs. Simulation studies show that SAFE properly controls error rates within and across SAs at the nominal level. We further apply the proposed approach to two case studies based on real data from the Historical Trial Data (HTD) Sharing Initiative of the DataCelerate platform. As compared to some direct methods, SAFE demonstrates an appealing feature of screening out extreme data and reaching solid safety conclusions. It can act as either a building block in another framework, or a platform to incorporate additional components.
The emergence of drug-resistant porcine enterotoxigenic Escherichia coli (ETEC) necessitates the exploration of alternative antibacterial approaches. Two lytic bacteriophages, PES-1 and PES-2, have been isolated and characterized to control ETEC. PES-1 exhibited a wide host range, lysing five ETEC strains, whereas PES-2 displayed restricted specificity, impacting only one of the seven strains. Both phages demonstrated optimal stability at a pH of 4.0-7.0 and a temperature of 4 °C-37 °C. Comparative genomic characterization revealed that the bacteriophages PES-1 have a 40.3 kb size and 48.29% GC contents, while the PES-2 have 67.8 kb size and 46.12% GC Contents, both of which possess a double-stranded linear DNA genomes, lacking tRNA genes, lysogeny-related elements, virulence factors, and antibiotic-resistant factors, emphasizing their obligately lytic lifestyle and genomic biosafety. Genomic analysis revealed that PES-1 exhibited sensitivity to EcoR-I and Hind-III. PES-2 demonstrated resistance to all tested restriction enzymes. Combining bacteriophages with antibiotics such as amoxicillin and neomycin significantly enhanced antibacterial efficacy (p < 0.05). A notable synergy was observed with amoxicillin, resulting in a decrease in bacterial loads by 2.02-3.47 log units compared to amoxicillin alone. This synergy likely arises from dual selective pressure and improved antibiotic penetration after phage-mediated lysis. However, no significant difference was observed in the gentamycin-phage combination group compared to the phage cocktail group. The results indicate that PES-1 and PES-2 show environmental stability and effectiveness as biocontrol agents for ETEC. This research introduces an innovative method for developing bacteriophage-based solutions applicable to veterinary and food safety contexts.
Glucocorticoids are widely used to relieve pain and inflammation in osteoarthritis (OA), yet repeated or high-dose exposure is associated with cartilage toxicity and systemic adverse effects. Mesenchymal stromal cell (MSC)-based therapies have emerged as a regenerative strategy. Whether clinically relevant, low-dose corticosteroid exposure can be integrated with MSC-based therapies remains unclear. Here, using a deliberately low-dose dexamethasone (DEX) regimen, we show that DEX preserves MSC viability, stemness, and anti-inflammatory polarization under pro-inflammatory stress in vitro, yet unexpectedly fails to enhance MSC-mediated joint repair in vivo in a papain-induced early-stage OA model. Mechanistically, DEX induces robust VEGF-C expression in MSCs, particularly under inflammatory conditions, and consequently promotes CD8+ T-cell accumulation and activation in the synovium. Notably, silencing of VEGF-C in MSCs restored therapeutic synergy between DEX and MSCs, resulting in improved cartilage integrity, enhanced proteoglycan preservation, and reduced synovial inflammation in a papain-induced OA model. This cooperative effect is further maintained in a surgically induced, mechanically driven late-stage OA model. Our findings establish VEGF-C silencing as a strategy to improve low-dose DEX-MSC therapeutic cooperation in OA.
This review presents an innovative "three-axis synergy" immunotherapeutic strategy for malignant bone tumors, combining natural bioactives with bioactive materials to overcome the challenges posed by the immunosuppressive microenvironment (IME) of tumors. Malignant bone tumors create an IME characterized by immune evasion, bone destruction, and physicochemical dysregulation, which limits the effectiveness of conventional therapies. Natural bioactives, known for their immunomodulatory effects, can potentially reprogram the IME, but their clinical application is hindered by low bioavailability and limited targeting efficiency. Bioactive materials, such as scaffolds and nanoparticles, can improve the delivery, retention, and targeted release of these bioactives, while also supporting bone regeneration. By combining natural bioactives with bioactive materials, this synergistic approach offers a dual-functional therapeutic platform that not only targets immune suppression but also promotes bone repair. This strategy addresses the key barriers of the IME, including immune imbalance, bone resorption, and physicochemical abnormalities. Although challenges remain in the clinical translation of these natural bioactives, their integration with bioactive materials provides a promising direction for improving treatment outcomes of malignant bone tumors. This approach offers new insights into the future of cancer immunotherapy and bone regeneration.
Although the co-delivery of chemotherapeutic agents and sonosensitizers has been studied for years, developing efficient co-delivery nanocarriers that combine chemotherapy and sonodynamic therapy (SDT) with precise targeting remains a challenge. In this study, we prepared folic acid (FA)-functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles (FPMD NPs) co-loaded with doxorubicin (Dox) and the sonosensitizer manganese(III) meso-tetrakis(4-carboxyphenyl)porphyrin (MnTPP) via a double-emulsion solvent evaporation method. Upon ultrasound irradiation, oxidative stress and apoptotic signaling were activated, which was revealed by transcriptomic analysis. In vivo, the combination of FPMD NPs with ultrasound achieved tumor targeting and tumor growth suppression in BALB/c nude mice bearing HNE-1 xenografts. The body weight of BALB/c nude mice remained stable and no histopathological abnormalities in major organs were detected. Overall, the FPMD NPs successfully integrate MnTPP-mediated SDT with Dox chemotherapy and demonstrate strong antitumor efficacy and favorable biosafety, highlighting their potential for synergistic SDT and chemotherapy in nasopharyngeal carcinoma treatment.
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. The therapeutic efficacy of conventional chemotherapeutic agents such as doxorubicin (DOX) is limited by dose-dependent toxicity and the development of drug resistance. Combination strategies incorporating bioactive natural products may enhance anticancer efficacy while enabling dose reduction. The present study aimed to evaluate the potential synergistic cytotoxicity of combining Fenugreek aqueous extract (FAE) with (DOX) against the HepG2 cell line. Phytochemical characterization was performed using UHPLC-QTOF-MS/MS Profiling and HPLC. Cell viability and selectivity were assessed using the SRB assay. Apoptosis, necrosis, autophagy, and cell cycle distribution were analysed by flow cytometry and Western blotting. Drug-drug interaction was evaluated using the Chou-Talalay method. Molecular docking was performed to explore potential interactions between selected FAE constituents and apoptosis- and autophagy-related protein targets. FAE enhanced DOX's cytotoxicity on HepG2 cells, with the interaction ranging from synergistic to additive depending on the concentration ratio. The DOX/FAE combination enhanced cell death through sub-G1 arrest and augmented apoptotic, necrotic, and autophagic responses compared with monotherapies. Western blot analysis demonstrated modulation of the Bax/Bcl-2 ratio and increased LC3-II expression. Docking simulations suggested favourable binding of selected steroidal saponins to Bcl-2 and LC3 proteins. These findings indicate that FAE potentiates DOX-induced cytotoxicity in vitro through modulation of multiple regulated cell death pathways. While the results support the possibility of this combination as a dose-modulating strategy, further validation in additional HCC models and in vivo systems is required.
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Weakly Supervised Semantic Segmentation (WSSS) remains highly challenging because image-level supervision typically produces class activation maps (CAMs) that are incomplete or noisy when used as pixel-level pseudo-labels. Despite the architectural efficiency of one-stage approaches, they are often hindered by tight encoder-label coupling: CAMs and segmentation predictions are derived from the same encoder and optimized jointly, leading to the propagation and reinforcement of initial CAM inaccuracies by the segmentation outputs. To circumvent this limitation, we propose SynerNet, a one-stage dual-branch framework that explicitly mandates complementary yet synergistic objectives: one branch generates broad pseudo-labels to enhance coverage, while the other produces precise pseudo-labels to sharpen localization. With such pseudo-labels, the segmentation network yields simultaneously comprehensive and accurate predictions. The broad branch (B-CAM) leverages global attention to expand foreground coverage by guiding ambiguous regions toward likely foreground, whereas the precise branch (P-CAM) emphasizes fine localization by encouraging unreliable pixels toward the background. Through cross-supervision, the two branches effectively decouple the optimization process, alleviating the risk of error reinforcement inherent in direct coupling. To further integrate their strengths, we introduce a confidence matrix derived from multi-scale ViT features, in which pixels consistently classified across layers are treated as high-confidence, while inconsistent ones are marked as uncertain. This enables a confidence-guided fusion strategy that directly adopts reliable predictions and adaptively blends uncertain regions using contributions from both branches. Such a complementary design mitigates error reinforcement and promotes mutually beneficial learning, enabling the network to generate high-fidelity pseudo-labels in a fully end-to-end manner. By combining branch-specific objectives with confidence-guided fusion, SynerNet produces pseudo-labels that are both complete and precise, achieves state-of-the-art performance on PASCAL VOC 2012 and COCO 2014, and demonstrates the effectiveness of one-stage co-training for high-quality weakly supervised segmentation. The code is publicly available at: https://github.com/ZhonggaiWang/DEFormer.
Carbon/metal compound composites offer significant performance and stability advantages for supercapacitor electrodes. However, conventional strategies struggle to concurrently achieve high metal content and dispersion within the carbon skeleton, both critically affecting energy storage performance and cycling stability. Separately, spent biochar adsorbents pose secondary pollution risks if improperly disposed of. To address these issues, the copper ion loading capacity of nanoplastics is enhanced by investigating the bidirectional promotive effect between nanoplastics and copper ions in aqueous systems: copper ions on the nanoplastics surface will promote their thermal oxidative decomposition. Meanwhile, the oxygen-containing functional groups generated by thermal oxidative decomposition strengthen the interaction between nanoplastics and copper ions, enabling higher copper ion loading on their surfaces, and forming a positive feedback loop. Subsequent co-processing of the nanoplastic system with biochar via nano-micro hybrid scale pyrolysis and activation ultimately yielded the carbon/copper oxide composite (CPC/CuOx), possessing a high specific surface area while concurrently achieving high metal dispersion and high metal content. As a supercapacitor electrode, CPC/CuOx delivered a high specific capacitance of 744 F·g-1 at 0.5 A·g-1 and maintained 80% capacitance retention after 10, 000 cycles. Therefore, this novel approach facilitates high-performance carbon/metal composites and provides a route to convert spent adsorbents into energy materials, mitigating leakage risks after environmental remediation.
As the use of pharmaceuticals and nanomaterials continues to rise, their concurrent presence in aquatic ecosystems has become increasingly likely, challenging primary producers with complex exposure conditions. Yet, the molecular mechanisms governing their joint impacts are still unclear. This study presents a multi-scale investigation of the time- and concentration-dependent interactions between ibuprofen (IBU) and graphene oxide (GO) in the green alga Chlorella vulgaris. Environmentally relevant concentrations (ERCs) and sublethal concentrations were used, with physiological screening integrated with transcriptomic and metabolomic analyses to assess the effects of IBU, GO, and their mixture (MIX) on algal growth, energy metabolism, and cellular vitality under both acute and chronic conditions. Multi-omics and physiological data revealed concentration-dependent disruptions of MIX in cellular energy metabolism, redox homeostasis, photosynthesis, and cofactor biosynthesis. IBU chiefly disturbed cellular energy pathways and redox homeostasis, consistent with mitochondrial dysfunction, while GO primarily impaired photosynthesis and caused pronounced oxidative stress. Under ERCs and acute conditions, exposure produced largely additive effects with instances of IBU-driven synergism. But the net interaction between IBU and GO shifted toward antagonism, with GO inducing more pronounced oxidative stress and exacerbated mitochondrial damage under sublethal and chronic conditions. By elucidating the time- and concentration- dependent mechanistic interplay between pharmaceuticals and nanomaterials, this work advances understanding of complex co-exposure effects in algae and highlights the importance of chronic, multi-endpoint omics approaches in ecological risk assessment.
Soil contamination by heavy metals (HMs) has intensified with industrialization, mining, and intensive agriculture, creating an urgent need for sustainable remediation strategies. Conventional chemical and physical techniques are costly, disruptive, and difficult to apply at the field scale, emphasizing eco-friendly biological alternatives. This study investigated the combined remediation potential of the microalga Haematococcus pluvialis (H. pluvialis) and three Festuca arundinacea varieties (Nilüfer, Grande II, and Jaguar 4G) for removing cadmium (Cd), lead (Pb), and zinc (Zn) from contaminated soil. Increasing H. pluvialis doses enhanced Cd, Pb, and Zn accumulation in shoots and roots while decreasing Pb bioaccumulation factors. Translocation factors and overall phytoremediation efficiency improved for all metals following microalgal application, with Grande II showing the highest recovery. Post-harvest soil analyses revealed reductions of 57.14%, 20.31%, and 25.46% in Cd, Pb, and Zn concentrations, respectively, alongside a 2.69% decline in soil pH and a 5.34% rise in organic matter. The most effective treatment was 1.5 g kg-1H. pluvialis with Grande II. These findings demonstrate that optimizing microalgal dosage improves metal removal efficiency and supports soil restoration, providing a foundation for sustainable phytoremediation applications.
To evaluate whether a deconstructed Tai Chi stepping protocol adapted for patients with Brunnstrom Stage III stroke, when combined with conventional rehabilitation, improves lower limb motor function, walking ability, and joint mobility compared with conventional rehabilitation plus limb synergy training. In this assessor-blinded randomized controlled trial, 52 patients with subacute stroke (Brunnstrom Stage III, ≤ 6 months post-stroke) were randomized in a 1:1 ratio to an experimental group (conventional rehabilitation plus adapted Tai Chi stepping training) or a control group (conventional rehabilitation plus limb synergy training). Both interventions were delivered 5 days per week for 8 weeks. Fifty participants completed the study and were included in the final per-protocol analysis (25 per group). Outcomes were assessed at baseline and after intervention. The primary outcomes were the Fugl-Meyer Assessment for Lower Extremity (FMA-LE) and Holden Walking Function Classification. Secondary outcomes were hip, knee, and ankle range of motion (ROM). Both groups improved after treatment, with greater improvement observed in the experimental group. FMA-LE scores increased by 5.6 ± 1.5 points in the experimental group and 1.8 ± 0.8 points in the control group (p < 0.001, Cohen's d = 1.32). In addition, 92% (23/25) of participants in the experimental group achieved Holden Grades II-III compared with 60% (15/25) in the control group (p < 0.001). The experimental group also showed larger gains in joint ROM, including hip flexion (+19.9° vs. + 4.2°), knee external rotation (+9.9° vs. + 3.7°), and ankle dorsiflexion (+7.6° vs. + 1.3°) (all p < 0.001). Deconstructed Tai Chi stepping training combined with conventional rehabilitation was associated with greater improvement in lower limb motor function, walking ability, and joint mobility than conventional rehabilitation plus limb synergy training in patients with Brunnstrom Stage III stroke. This stage-specific protocol may represent a practical adjunct to stroke rehabilitation, although confirmation in larger trials is still needed. International Traditional Medicine Clinical Trial Registry (ITMCTR; a WHO ICTRP Primary Registry), registration number ITMCTR2025000972.
Combination therapies have become a cornerstone of modern medicine, offering improved treatment outcomes and reduced side effects compared to monotherapies. However, the efficacy and safety of drug combinations depend heavily on the specific doses of each component, making the optimization of dosing regimens a crucial yet challenging task. Despite the importance of dose optimization, few computational methods address this challenge. Here, we propose DeepDRP, a novel approach that integrates two complementary models: the global model, which is trained using all available combinations, and the local model, which utilizes only samples with similar information to queries. The DeepDRP architecture comprises three main modules: the first module has three embedding networks to extract features from drugs, doses, and cell lines, and then predicts synergy using the fused knowledge. The second module constructs a graph using the input query and the set of similar retrieved training samples fed into a semi-supervised graph convolutional network to predict the synergy value. Finally, these two models are aggregated to have the final predicted value. To evaluate the proposed approach, it is applied to the NCI-ALMANAC dataset and O'Neil dataset. The obtained results denote that the proposed method achieves superior performance with respect to the other approaches.
This research investigates the critical, under-examined nexus of geopolitical risk, environmental quality (CO2 emissions), and public health in BRICS countries. Employing pooled and quantile regression estimators for panel data, the study reveals that geopolitical risk is positively associated with environmental quality, in turn, exacerbating PM2.5 concentrations. Notably, the interaction between geopolitical risk and environmental quality amplifies the negative impact on public health and life expectancy. This highlights a precarious synergy: geopolitical instability intensifies the adverse health effects of environmental pollution. The study's novelty lies in its comprehensive, integrated approach to this complex relationship. Our findings highlight the urgent need for policymakers to adopt holistic strategies that integrate geopolitical stability with environmental and public health agendas, particularly in these rapidly emerging economies.
Nanocellulose, extracted from the most abundant renewable resource in nature, features environmental friendliness, wide availability, high specific surface area and high mechanical strength. The modification aimed at expanding its applications often only alters the chemical structure of its surface, with less focus on simultaneously regulating its surface morphology. This work used cellulose nanocrystals (CNCs) as a template and employed 3-aminopropyltriethoxysilane (APTES) along with inorganic nanoparticle precursors (represented by tetraethoxysilane) for the synergistic modification of CNCs. A strategy was developed to achieve the simultaneous introduction of amino-silane groups and the deposition of SiO2 nanoparticles on the CNC surface in a controllable manner. Moreover, the underlying mechanism of the synergistic modification was elucidated based on various characterization methods. The modified CNCs exhibited not only improved thermal stability but also an increase in specific surface area from 1.54 to 149.20 m2/g. Upon extending this modification approach to APTES in synergy with FeCl3.6H2O, the modified CNCs exhibited the photocatalytic degradation capability towards methylene blue dye, achieving a degradation ratio of up to 86.76%. This work provides a mild strategy to regulate the surface structure and functionality of CNCs.
This invited commentary grew out of a presentation made at the 2025 ConRad Meeting in Munich, Germany, and summarizes talks made by researchers supported by the National Institute of Allergy and Infectious Diseases (NIAID) and the Bundeswehr Institute of Radiobiology (BIR) during a joint programmatic workshop held on September 11-12, 2024. The symposium focused on the global health readiness and responses to radiological or nuclear public health emergencies; the status of medical countermeasure development and models used to develop these countermeasures; identification of biomarkers of radiation injuries and biodosimetry tools, and recent advances in developing tools for triage, definitive dose assessment and predictive assays. Areas of common synergy between the two entities were also explored to inform potential future collaborative efforts. There are many tools at different stages of development, and emergence of substantive datasets that require cutting-edge machine learning approaches, multiparametric analyses, and integrated systems outcome to fully exploit the potential of this knowledge and accurately address radiological emergency preparedness. In these endeavors, now more than ever, it is critical to continue connecting with the world's scientific communities to accelerate scientific breakthroughs, close research gaps, and enhance radiation emergency readiness.
Electromagnetic shielding materials offer excellent resistance to electromagnetic interference, yet their application remains constrained by single-functionality in complex environments. Herein, we fabricate a novel electromagnetic shielding smart window featuring fast-response characteristics. The proposed smart window is constructed based on a self-assembly layered gel network, which is synthesized using two-dimensional Laponite XLG and N-isopropylacrylamide (NIPAM) as the matrix, coupled with functional modification via metal ions. Metal ions doped in the system effectively enhance the electrical conductivity of the material, enabling a maximum electromagnetic shielding effectiveness (SET) of 72.49 dB. Furthermore, this unique layered architecture endows the system with enhanced stability and structural order, while simultaneously reducing mass transfer resistance associated with light transmission and heat conduction, thereby accelerating the responsive behavior of materials. Specifically, SCa-1 exhibits a luminous transmittance (Tlum) of 83.49% and a large solar modulation (ΔTsol) of 82.57%, which achieves a rapid thermochromic response within 20 s at 60°C. This work clarifies the role of layered structural design in optimizing system stability and order, revealing the fundamental mechanisms underlying the synergy between electromagnetic shielding and thermochromic properties, which provides a novel strategy for designing smart electromagnetic protection materials.
Previous evidence regarding the combined effects of metabolic disorders on intestinal barrier function (IBF) remains limited. We hypothesized that metabolic disorders interact to increase the risk of intestinal barrier dysfunction. This retrospective case-control study included 4,289 individuals who underwent IBF assessment. Controls with normal biomarker levels were propensity score-matched to cases with abnormal D-lactic acid, diamine oxidase (DAO), or endotoxin. Logistic regression and interaction models were applied to assess associations between metabolic indicators and intestinal barrier dysfunction. Hypertension (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.20-1.55; P< 0.001), dyslipidemia (OR, 1.70; 95% CI, 1.49-1.96; P< 0.001), and hyperglycemia (OR, 1.80; 95% CI, 1.57-2.08; P< 0.001) were significantly associated with intestinal barrier dysfunction. Subgroup analyses confirmed that dyslipidemia and hyperglycemia were independently associated with elevated DAO, D-lactic acid, and endotoxin levels. Both multiplicative and additive interactions were observed between key metabolic factors. Particularly, dyslipidemia and hyperglycemia showed significant additive interactions (relative excess risk due to interaction, 0.79 [95% CI, 0.19-1.35, P= 0.008]; attributable proportion due to interaction, 0.29 [95% CI, 0.06-0.46, P= 0.008]; synergy index, 1.82 [95% CI, 1.13-3.41, P= 0.008]). When stratified by age and sex, broadly similar trends were observed in participants aged ≥ 50 years and in males. Dyslipidemia and hyperglycemia are associated with intestinal barrier dysfunction and show a synergistic combined effect. Individuals with both should receive prioritized IBF monitoring and early metabolic intervention to protect barrier integrity.
We report a high-resolution rotational study of N-methylmaleimide and N-methylsuccinimide using a molecular jet Ka-band Chirped Pulse Fourier-Transform MicroWave (CP-FTMW) spectrometer and two resonator-based FTMW instruments (Passage And Resonance In Synergy─PARIS and Ka-band "small cavity"). In both molecules, the methyl group undergoes facile internal rotation, splitting each rotational transition into the m = 0 and m = 1 torsional species. For N-methylmaleimide, 672 hyperfine-resolved transitions were assigned from the PARIS (2-20 GHz) and "small cavity" data. A global fit using the XIAM program yielded an rms deviation of 89.1 kHz, and separate fits of the two torsional species confirmed the correctness of the assignment. The program BELGIimproved the rms deviation to 4.5 kHz, consistent with the measurement accuracy. For N-methylsuccinimide, 260 transitions were assigned from the Ka-band CP-FTMW spectra with a measurement accuracy of 25 kHz. The data were fitted first with the XIAM program to an rms deviation of 32.7 kHz, and then with the BELGI program, which reduced this value to 24.9 kHz. The V6 torsional barriers were determined to be 20.2364(16) cm-1 for N-methylmaleimide and 25.833(11) cm-1 for N-methylsuccinimide. These values are significantly lower than that of N-methylpyrrole (67.8 cm-1), suggesting that the two adjacent carbonyl substituents enhance the sensitivity of the methyl rotor to the local C2v electronic environment, thereby lowering the torsional barrier.
Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) are attractive building blocks for bioelectronics owing to their programmable porous structures, rich host-guest chemistry, and tailorable functionalities. Organic photoelectrochemical transistors (OPECTs), which couple light-addressable redox transduction of photoelectrochemical sensing with the intrinsic signal amplification of organic transistors, have recently emerged as promising bioanalysis platforms. By synergizing the functionalities of MOFs and COFs, here we present a cathodic OPECT bioanalysis by using a hemin-incorporated ZIF-8 (Hemin@ZIF-8) biological MOF (bioMOF) to augment the performance of a photocathodic TpPa-Cl COF. The platform operates via a split-type cortisol-targeted sandwich immunorecognition using glucose oxidase (GOx)-labeled detection antibodies, where the immunocaptured GOx catalyzes the oxidation of glucose to gluconic acid, leading to the disintegration of the pH-responsive bioMOF on the gate and thus the release of encapsulated hemin. The released hemin serves as an efficient electron acceptor for photoexcited electrons in the photocathodic COF, suppressing carrier recombination and enhancing the photoelectric response of the device. The as-developed cathodic OPECT delivers sensitive cortisol detection with an ultralow detection limit of 1.0 fg mL-1. By harnessing the synergy between bioMOFs and COFs, this work introduces a novel approach to gate OPECTs, revealing their potential for high-performance optoelectronic bioanalysis.