Electrocatalytic water-to-oxygenates conversion: redox-mediated versus direct oxygen transfer.

Electrocatalytic oxygenation of hydrocarbons with high selectivity has attracted much attention for its advantages in the sustainable and controllable production of oxygenated compounds with reduced greenhouse gas emissions. Especially when utilizing water as an oxygen source, by constructing a water-to-oxygenates conversion system at the anode, the environment and/or energy costs of producing oxygenated compounds and hydrogen energy can be significantly reduced. There is a broad consensus that the generation and transformation of oxygen species are among the decisive factors determining the overall efficiency of oxygenation reactions. Thus, it is necessary to elucidate the oxygen transfer process to suggest more efficient strategies for electrocatalytic oxygenation. Herein, we introduce oxygen transfer routes through redox-mediated pathways or direct oxygen transfer methods. Especially for the scarcely investigated direct oxygen transfer at the anode, we aim to detail the strategies of catalyst design targeting the efficient oxygen transfer process including activation of organic substrate, generation/adsorption of oxygen species, and transformation of oxygen species for oxygenated compounds. Based on these examples, the significance of balancing the generation and transformation of oxygen species, tuning the states of organic substrates and intermediates, and accelerating electron transfer for organic activation for direct oxygen transfer has been elucidated. Moreover, greener organic synthesis routes through heteroatom transfer and molecular fragment transfer are anticipated beyond oxygen transfer.

Combined detection of serum EFNA1 and MMP13 as diagnostic biomarker for gastric cancer.

We previously identified that serum EFNA1 and MMP13 were potential biomarker for early detection of esophageal squamous cell carcinoma. In this study, our aim is to explore the diagnostic value of serum EFNA1 and MMP13 for gastric cancer. We used enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of serum EFNA1 and MMP13 in 210 GCs and 223 normal controls. The diagnostic value of EFNA1 and MMP13 was evaluated in an independent cohorts of GC patients and normal controls (n = 238 and 195, respectively). Receiver operating characteristics were used to calculate diagnostic accuracy. In training and validation cohorts, serum EFNA1 and MMP13 levels in the GC groups were significantly higher than those in the normal controls (P < 0.001). The area under the curve (AUC) of the combined detection of serum EFNA1 and MMP13 for GC was improved (0.794), compared with single biomarker used. Similar results were observed in the validation cohort. Importantly, the combined measurement of serum EFNA1 and MMP13 to detect early-stage GC also had acceptable diagnostic accuracy in training and validation cohort. Combined detection of serum EFNA1 and MMP13 could help identify early-stage GC, suggesting that it may be a promising tool for the early detection of GC.

Long-term trend and interannual variation in evapotranspiration of a young temperate Douglas-fir stand over 2002-2022 reveals the impacts of climate change.

The shortage of decades-long continuous measurements of ecosystem processes limits our understanding of how changing climate impacts forest ecosystems. We used continuous eddy-covariance and hydrometeorological data over 2002-2022 from a young Douglas-fir stand on Vancouver Island, Canada to assess the long-term trend and interannual variability in evapotranspiration (ET) and transpiration (T). Collectively, annual T displayed a decreasing trend over the 21 years with a rate of 1% yr-1, which is attributed to the stomatal downregulation induced by rising atmospheric CO2 concentration. Similarly, annual ET also showed a decreasing trend since evaporation stayed relatively constant. Variability in detrended annual ET was mostly controlled by the average soil water storage during the growing season (May-October). Though the duration and intensity of the drought did not increase, the drought-induced decreases in T and ET showed an increasing trend. This pattern may reflect the changes in forest structure, related to the decline in the deciduous understory cover during the stand development. These results suggest that the water-saving effect of stomatal regulation and water-related factors mostly determined the trend and variability in ET, respectively. This may also imply an increase in the limitation of water availability on ET in young forests, associated with the structural and compositional changes related to forest growth.

Electron Divergence of Cuδ- and Pdδ+ in Cu3Pd Alloy-Based Heterojunctions Boosts Concerted C≡C Bond Binding and the Volmer Step for Alkynol Semihydrogenation.

Electrocatalytic semihydrogenation of alkynols presents a sustainable alternative to conventional thermal methodologies for the high-value production of alkenols. The design of efficient catalysts with superior catalytic and energy efficiency for semihydrogenation poses a significant challenge. Here, we present the application of an electron-divergent Cu3Pd alloy-based heterojunction in promoting the electrocatalytic semihydrogenation of alkynols to alkenols using water as the proton source. The tunable electron divergence of Cuδ- and Pdδ+, modulated by rectifying contact with nitrogen-rich carbons, enables the concerted binding of active H species from the Volmer step of water dissociation and the C≡C bond of alkynols on Pdδ+ sites. Simultaneously, the pronounced electron divergence of Cu3Pd facilitates the universal adsorption of OH species from the Volmer step and alkynols on the Cuδ- sites. The electron-divergent dual-center substantially boosts water dissociation and inhibition of completing hydrogen evolution to give a turnover frequency of 2412 h-1, outperforming the reported electrocatalysts' value of 7.3. Moreover, the continuous production of alkenols at industrial-related current density (-200 mA cm-2) over the efficient and durable Cu3Pd-based electrolyzer could achieve a cathodic energy efficiency of 45 mol kW·h-1, 1.7 times the bench-marked reactors, promising great potential for sustainable industrial synthesis.

Competitive electrochemical aptasensor for high sensitivity detection of liver cancer marker GP73 based on rGO-Fc-PANi nanocomposites.

Golgi protein 73 (GP73) is a novel tumor marker in the early diagnosis and prognosis of hepatocellular carcinoma (HCC). Herein, a competitive electrochemical aptasensor for detecting GP73 was constructed using reduced graphene oxide-ferrocene-polyaniline nanocomposite (rGO-Fc-PANi) as the biosensing platform. The rGO-Fc-PANi had larger specific surface area, excellent conductivity and outstanding electroactive performance, which served as nanocarrier for GP73 aptamer (GP73Apt) binding and as redox nanoprobe for record electrical signal. Then, a complementary chain (cDNA) was fixed to the electrode by hybridization with GP73Apt. When GP73 was present, a competitive process happened among cDNA, GP73Apt and GP73, formed the GP73-GP73Apt stable chemical structure and made cDNA detach from the sensing electrode, resulting in enhancement of electrical signal. The difference in the corresponding peak current before and after the competition can be used to indicate the quantitative of GP73. Under optimal conditions, the DPV current response showed a good log-linear relationship with GP73 concentrations (0.001 âˆ¼ 100.0 ng/mL) with a detection limit of 0.15 pg/mL (S/N = 3). It was successfully used for GP73 detection in human serum with RSDs ranging from 1.08 % to 6.96 %. Therefore, the aptasensor could provide an innovative technology platform and hold a great potential in clinical application.

[Environmental regulation of water use efficiency in Artemisia ordosica in Mu Us Sandy Land: From leaf to ecosystem]. / æ¯›ä¹Œç´ æ²™åœ°é»‘æ²™è’¿æ°´åˆ†åˆ©ç”¨æ•ˆçŽ‡çŽ¯å¢ƒè°ƒæŽ§:从叶片到生态系统.

Water use efficiency (WUE) is a key indicator for predicting the impacts of climate change on ecosystem carbon and water cycles. Most studies have explored the changes in the response environment of WUE at a particular scale. Few studies have examined how WUE responds to environments at multiple scales, thus limiting our in-depth understanding of the cross-scale carbon and water cycles. In this study, we measured photosynthesis and transpiration in situ periodically and continuously from June to October 2022 in a community dominated by Artemisia ordosica in Mu Us Sandy Land, and analyzed the seasonal variations in WUE at leaf, canopy, and ecosystem scales. The results showed there were significant seasonal variations in leaf water use efficiency (WUEL), canopy water use efficiency (WUET), and ecosystem water use efficiency (WUEE). WUEL was large in June and small in both August and September, ranging from 0.73-2.98 µmol·mmol-1. Both WUET and WUEE were lowest in June and highest in July and August, ranging from 0.10-7.00 and 0.06-6.25 µmol·mmol-1. WUEL was significantly negatively correlated with stomatal conductance. WUET was significantly positively correlated with canopy conduc-tance and soil water content, and negatively correlated with vapor pressure deficit (VPD). There was a significant positive correlation between WUEE and soil water content (SWC10) in 10 cm soil depth. The structural equation model showed that SWC10 and air temperature affected net photosynthetic rate and transpiration rate by modifying stomatal conductance, and thus affecting WUEL. VPD and SWC10 affected WUET by altering transpiration. SWC10, air temperature, and VPD affected WUEE by regulating ecosystem gross primary productivity. The modelling of carbon and water cycles should thoroughly consider the path and intensity of the effect of environmental factors on WUE at multiple scales.

A review: targeting UBR5 domains to mediate emerging roles and mechanisms: chance or necessity?

Ubiquitinases are known to catalyze ubiquitin chains on target proteins to regulate various physiological functions like cell proliferation, autophagy, apoptosis, and cell cycle progression. As a member of E3 ligase, ubiquitin protein ligase E3 component n-recognin 5 (UBR5) belongs to the HECT E3 ligase and has been reported to be correlated with various pathophysiological processes. In this review, we give a comprehensive insight into the structure and function of UBR5. We discuss the specific domains of UBR5 and explore their biological functions separately. Furthermore, we describe the involvement of UBR5 in different pathophysiological conditions, including immune response, virus infection, DNA damage response and protein quality control. Moreover, we provide a thorough summary of the important roles and regulatory mechanisms of UBR5 in cancers and other diseases. On the whole, investigating the domains and functions of UBR5, elucidating the underlying mechanisms of UBR5 with various substrates in detail may provide new theoretical basis for the treatment of diseases, including cancers, which could improve future studies to construct novel UBR5-targeted therapy strategies.

Topology Prediction of Gas-Separating Metal-Organic Frameworks with Low Symmetry Vertices.

Topology serves as a blueprint for the construction of reticular structures such as metal-organic frameworks, especially for those based on building blocks with highly symmetrical shapes. However, it remains a challenge to predict the topology of the frameworks from less symmetrical units, because their corresponding vertex figures are largely deformed from the perfect geometries with no "default" net embedding. Furthermore, vertices involving flexible units may have multiple shape choices, and the competition among their designated topologies makes the structure prediction in large uncertainty. Herein, the deformation index is proposed to characterize the symmetry loss of the vertex figure by comparing it with its ideal geometry. The mathematical index is employed to predict the shapes of two in situ formed Co-based metalloligands (pseudo-tetrahedron and pseudo-square), which further dictate the framework topology (flu and scu) when they are joined with the [Zr6O8]-based cuboid units. The two frameworks with very similar constituents provide an ideal platform to investigate how the pore shapes and interconnectivity influence the gas separation. The net with cylindrical channels outperforms the other with discreate cages in C3H8/C2H6/CH4 separation, benefiting from the facile accessibility of its interaction sites to the guests imposed by the specific framework topology.

Numerical evaluation of internal femur osteosynthesis based on a biomechanical model of the loading in the proximal equine hindlimb.

Femoral fractures are often considered lethal for adult horses because femur osteosynthesis is still a surgical challenge. For equine femur osteosynthesis, primary stability is essential, but the detailed physiological forces occurring in the hindlimb are largely unknown. The objective of this study was to create a numerical testing environment to evaluate equine femur osteosynthesis based on physiological conditions. The study was designed as a finite element analysis (FEA) of the femur using a musculoskeletal model of the loading situation in stance. Relevant forces were determined in the musculoskeletal model via optimization. The treatment of four different fracture types with an intramedullary nail was investigated in FEA with loading conditions derived from the model. The analyzed diaphyseal fracture types were a transverse (TR) fracture, two oblique fractures in different orientations (OB-ML: medial-lateral and OB-AP: anterior-posterior) and a "gap" fracture (GAP) without contact between the fragments. For the native femur, the most relevant areas of increased stress were located distally to the femoral head and proximally to the caudal side of the condyles. For all fracture types, the highest stresses in the implant material were present in the fracture-adjacent screws. Maximum compressive (-348 MPa) and tensile stress (197 MPa) were found for the GAP fracture, but material strength was not exceeded. The mathematical model was able to predict a load distribution in the femur of the standing horse and was used to assess the performance of internal fixation devices via FEA. The analyzed intramedullary nail and screws showed sufficient stability for all fracture types.

A dual-signal output electrochemical aptasensor for glypican-3 ultrasensitive detection based on reduced graphene oxide-cuprous oxide nanozyme catalytic amplification strategy.

Glypican-3 (GPC3) is an essential reference target for hepatocellular carcinoma detection, follow-up and prediction. Herein, a dual-signal electrochemical aptasensor based on reduced graphene oxide-cuprous oxide (RGO-Cu2O) nanozyme was developed for GPC3 detection. The RGO-Cu2O nanoenzyme displayed excellent electron transport effect, large specific surface area and outstanding peroxidase-like ability. The differential pulse voltammetry (DPV) signal of Cu2O oxidation fraction and the chronoamperometry (i-t) signal of H2O2 decomposition catalyzed by RGO-Cu2O nanozyme were used as dual-signal detection. Under optimal conditions, the log-linear response ranges were 0.1 to 500.0 ng/mL with the limit of detection 0.064 ng/mL for DPV technique, and 0.1-50.0 ng/mL for i-t technique (detection limit of 0.0177 ng/mL). The electrochemical aptasensor has remarkably analytical performance with wide response range, low detection limit, excellent repeatability and specificity, good recovery in human serum samples. The two output signals of one sample achieve self-calibration of the results, effectively avoiding the occurrence of possible leakage and misdiagnosis of a single detection signal, suggesting that it will be a promising method in the early biomarker detection.

AURKA emerges as a vulnerable target for KEAP1-deficient non-small cell lung cancer by activation of asparagine synthesis.

AURKA is an established target for cancer therapy; however, the efficacy of its inhibitors in clinical trials is hindered by differential response rates across different tumor subtypes. In this study, we demonstrate AURKA regulates amino acid synthesis, rendering it a vulnerable target in KEAP1-deficient non-small cell lung cancer (NSCLC). Through CRISPR metabolic screens, we identified that KEAP1-knockdown cells showed the highest sensitivity to the AURKA inhibitor MLN8237. Subsequent investigations confirmed that KEAP1 deficiency heightens the susceptibility of NSCLC cells to AURKA inhibition both in vitro and in vivo, with the response depending on NRF2 activation. Mechanistically, AURKA interacts with the eIF2α kinase GCN2 and maintains its phosphorylation to regulate eIF2α-ATF4-mediated amino acid biosynthesis. AURKA inhibition restrains the expression of asparagine synthetase (ASNS), making KEAP1-deficient NSCLC cells vulnerable to AURKA inhibitors, in which ASNS is highly expressed. Our study unveils the pivotal role of AURKA in amino acid metabolism and identifies a specific metabolic indication for AURKA inhibitors. These findings also provide a novel clinical therapeutic target for KEAP1-mutant/deficient NSCLC, which is characterized by resistance to radiotherapy, chemotherapy, and targeted therapy.

Strain Regulation of Mixed-Halide Perovskites Enables High-Performance Wide-Bandgap Photovoltaics.

Wide-bandgap mixed-halogen perovskite materials are widely used as top cells in tandem solar cells. However, serious open-circuit voltage (Voc) loss restricts the power conversion efficiency (PCE) of wide-bandgap perovskite solar cells (PSCs). Herein, it is shown that the resulting methylammonium vacancies induce lattice distortion in methylammonium chloride-assisted perovskite film, resulting in an inhomogeneous halogen distribution and low Voc. Thus, a lattice strain regulation strategy is reported to fabricate high-performance wide-bandgap PSCs. Rubidium (Rb) cations are introduced to fill the A-site vacancy caused by the methylammonium volatilization, which alleviates shrinkage strain of the perovskite crystal. The reduced lattice distortion and increased halide ion migration barrier result in a homogeneous mixed-halide perovskite film. Due to improved carrier transport and suppressed nonradiative recombination, the Rb-treated wide-bandgap PSC (1.68 eV) achieves an excellent PCE of 21.72%, accompanied by a high Voc of 1.22 V. The resulting device maintains more than 90% of its initial PCE after 1500 h under 1-sun illumination conditions.

Design, synthesis and evaluation of C-5 substituted pyrrolopyridine derivatives as potent Janus Kinase 1 inhibitors with excellent selectivity.

The development of highly selective Janus Kinase 1 (JAK1) inhibitors is crucial for improving efficacy and minimizing adverse effects in the clinical treatment of autoimmune diseases. In a prior study, we designed a series of C-5 4-pyrazol substituted pyrrolopyridine derivatives that demonstrated significant potency against JAK1, with a 10 âˆ¼ 20-fold selectivity over Janus Kinase 2 (JAK2). Building on this foundation, we adopted orthogonal strategy by modifying the C-5 position with 3-pyrazol/4-pyrazol/3-pyrrol groups and tail with substituted benzyl groups on the pyrrolopyridine head to enhance both potency and selectivity. In this endeavor, we have identified several compounds that exhibit excellent potency and selectivity for JAK1. Notably, compounds 12b and 12e, which combined 4-pyrazol group at C-5 site and meta-substituted benzyl tails, displayed IC50 value with 2.4/2.2 nM and high 352-/253-fold selectivity for JAK1 over JAK2 in enzyme assays. Additionally, both compounds showed good JAK1-selective in Ba/F3-TEL-JAK1/2 cell-based assays. These findings mark a substantial improvement, as these compounds are 10-fold more potent and over 10-fold more selective than the best compound identified in our previous study. The noteworthy potency and selectivity properties of compounds 12b and 12e suggest their potential utility in furthering the development of drugs for autoimmune diseases.

Serum IGFBP-1 as a promising diagnostic and prognostic biomarker for colorectal cancer.

Our previous study showed that levels of circulating insulin-like growth factor binding protein-1 (IGFBP-1) has potential diagnostic value for early-stage upper gastrointestinal cancers. This study aimed to assess whether serum IGFBP-1 is a potential diagnostic and prognostic biomarker for CRC patients. IGFBP-1 mRNA expression profile data of peripheral blood in colorectal cancer (CRC) patients were downloaded and analyzed from Gene Expression Omnibus database. We detected serum IGFBP-1 in 138 CRC patients and 190 normal controls using enzyme-linked immunosorbent assay. Blood IGFBP-1 mRNA levels were higher in CRC patients than those in normal controls (P = 0.027). In addition, serum IGFBP-1 protein levels in the CRC group were significantly higher than those in normal control group (P < 0.0001). Serum IGFBP-1 demonstrated better diagnostic accuracy for all CRC and early-stage CRC, respectively, when compared with carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA 19-9) or the combination of CEA and CA19-9. Furthermore, Cox multivariate analysis revealed that serum IGFBP-1 was an independent prognostic factor for OS (HR = 2.043, P = 0.045). Our study demonstrated that serum IGFBP-1 might be a potential biomarker for the diagnosis and prognosis of CRC. In addition, the nomogram might be helpful to predict the prognosis of CRC.

A stepwise strategy integrating dynamic stress CT myocardial perfusion and deep learning-based FFRCT in the work-up of stable coronary artery disease.

OBJECTIVES: To validate a novel stepwise strategy in which computed tomography-derived fractional flow reserve (FFRCT) is restricted to intermediate stenosis on coronary computed tomography angiography (CCTA) and computed tomography myocardial perfusion imaging (CT-MPI) was reserved for vessels with gray zone FFRCT values. MATERIALS AND METHODS: This retrospective study included 87 consecutive patients (age, 58 ± 10 years; 70% male) who underwent CCTA, dynamic CT-MPI, interventional coronary angiography (ICA), and fractional flow reserve (FFR) for suspected or known coronary artery disease. FFRCT was computed using a deep learning-based platform. Three stepwise strategies (CCTA + FFRCT + CT-MPI, CCTA + FFRCT, CCTA + CT-MPI) were constructed and their diagnostic performance was evaluated using ICA/FFR as the reference standard. The proportions of vessels requiring further ICA/FFR measurement based on different strategies were noted. Furthermore, the net reclassification index (NRI) was calculated to ascertain the superior model. RESULTS: The CCTA + FFRCT + CT-MPI strategy yielded the lowest proportion of vessels requiring additional ICA/FFR measurement when compared to the CCTA + FFRCT and CCTA + CT-MPI strategies (12%, 22%, and 24%). The CCTA + FFRCT + CT-MPI strategy exhibited the highest accuracy for ruling-out (91%, 84%, and 85%) and ruling-in (90%, 85%, and 85%) functionally significant lesions. All strategies exhibited comparable sensitivity for ruling-out functionally significant lesions and specificity for ruling-in functionally significant lesions (p > 0.05). The NRI indicated that the CCTA + FFRCT + CT-MPI strategy outperformed the CCTA + FFRCT strategy (NRI = 0.238, p < 0.001) and the CCTA + CT-MPI strategy (NRI = 0.233%, p < 0.001). CONCLUSIONS: The CCTA + FFRCT + CT-MPI stepwise strategy was superior to the CCTA + FFRCT strategy and CCTA+ CT-MPI strategy by minimizing unnecessary invasive diagnostic catheterization without compromising the agreement rate with ICA/FFR. CLINICAL RELEVANCE STATEMENT: Our novel stepwise strategy facilitates greater confidence and accuracy when clinicians need to decide on interventional coronary angiography referral or deferral, reducing the burden of invasive investigations on patients. KEY POINTS: • A stepwise CCTA + FFRCT + CT-MPI strategy holds promise as a viable method to reduce the need for invasive diagnostic catheterization, while maintaining a high level of agreement with ICA/FFR. • The CCTA + FFRCT + CT-MPI strategy performed better than the CCTA + FFRCT and CCTA + CT-MPI strategies. • A stepwise CCTA + FFRCT + CT-MPI strategy allows to minimize unnecessary invasive diagnostic catheterization and helps clinicians to referral or deferral for ICA/FFR with more confidence.

Effects of microplastics on N2O production and reduction potential in crop soils of northern China.

Microplastics (MPs) pollution are found to be increasing in vegetable soils and potentially affecting N2O production and their associated pathways; however, its specific effects remain unclear. Here, we selected two common MPs, PE and PP at four different concentration levels of 0, 0.5, 1.5 and 3%, and conducted several incubation experiments aiming to explore soil bacterial and fungal N2O production. Results showed that the bacteria were the main contributors for the production of N2O, regardless of the absence or presence of MPs; and its contribution was decreased with increasing concentrations of PE and PP. The nosZ clade I and II genes were positively correlated with N2O reduction rates, indicating a combined regulation on soil N2O reduction. PE significantly inhibited the bacterial nitrification and denitrification, but did not affect the total N2O production rates; while PP significantly reduced both the bacterial and fungal N2O production rates. The resistance of fungal N2O production to MPs pollution was stronger than that of the bacterial N2O production. It highlights that the MPs pollution could reduce the potential of N2O production and reduction, and thus disturb soil nitrogen cycling system; while the inhibition on N2O production via bacteria and fungi varies with different types of MPs. This study is conducive to an improved and more comprehensive understanding of the ecological impacts of MPs within the agroecosystem.

The Presence, Location, and Degree of Late Gadolinium Enhancement in Relation to Myocardial Dysfunction and Poor Prognosis in Patients with Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) typically develop myocardial fibrosis. No studies have investigated the clinical significance of the presence, location, and degree of fibrosis in SLE patients. Seventy-four SLE patients were included. Thirty-seven non-autoimmune disease patients and thirty-seven healthy individuals were included as controls. Myocardial fibrosis was evaluated at cardiac magnetic resonance via a qualitative and quantitative assessment of late gadolinium enhancement (LGE). Myocardial function was measured via speckle-tracking echocardiography. All patients were followed up for the occurrence of major adverse cardiac events (MACE). The presence, locations, and degrees of LGE disturbed regional and global myocardial function. The presence of LGE, left ventricular free-wall LGE (LVFW LGE), and severe LGE were all independent predictors of MACE in SLE patients [LGE presence HR: 3.746 (1.434-9.79), p = 0.007; LVFW LGE HR: 2.395 (1.023-5.606), p = 0.044; severe LGE HR: 3.739 (1.241-11.266), p = 0.019]. LGE combined with SLE-related organ damage identified patients at high risk of MACE (p < 0.001). In conclusion, the presence, degree, and location of LGE were associated with myocardial dysfunction. The presence, location, and degree of LGE had the potential to independently predict poor prognosis and improve risk stratification in SLE patients.

A cascade signal-amplified fluorescent biosensor combining APE1 enzyme cleavage-assisted target cycling with rolling circle amplification.

A cascade signal-amplified fluorescent biosensor was developed for miRNA-21 detection by combining APE1 enzyme-assisted target recycling and rolling circle amplification strategy. A key feature of this biosensor is its dual-trigger mechanism, utilizing both tumor-endogenous miRNA-21 and the APE1 enzyme in the initial amplification step, followed by a second rolling circle amplification reaction. This dual signal amplification cascade significantly enhanced sensitivity, achieving a detection limit of 3.33 pM. Furthermore, this biosensor exhibited excellent specificity and resistance to interference, allowing it to effectively distinguish and detect the target miRNA-21 in the presence of multiple interfering miRNAs. Moreover, the biosensor maintained its robust detection capabilities in a 10% serum environment, demonstrating its potential for clinical disease diagnosis applications.