Acute pulmonary embolism (PE) remains a leading cause of cardiovascular mortality, driven primarily by a sudden increase in pulmonary artery (PA) resistance. Brain Natriuretic Peptide (BNP) may hold promise for reducing PA resistance. However, its role and mechanism in acute PE are not yet fully understood. This study aims to determine whether BNP alleviates PE-induced pulmonary vasoconstriction by targeting Natriuretic Peptide Receptor C (NPRC) and evaluate its therapeutic potential. Here, we established an acute PE rat model using autologous thrombi, and right ventricle (RV) pressure was monitored to approximate PA resistance. A small group of intermediate-high-risk acute PE patients were observed, who received BNP in addition to anticoagulation, and their clinical outcomes were compared to matched patients receiving anticoagulation alone. BNP at varying doses was administered to optimize therapeutic efficacy in the acute PE rat model. Mechanistic studies assessed BNP's impact on oxidative stress in PA endothelium. In the rats, BNP infusion significantly reduced RV pressure overload and improved survival. Clinically, patients receiving adjunctive BNP experienced more rapid improvement in heart rate, oxygen saturation, and blood pressure stability than anticoagulation alone. BNP decreased NADPH oxidase 2-dependent ROS levels in rats' PA endothelium, thereby reducing myosin light chain phosphorylation in smooth muscle. NPRC, as the central receptor, antagonizes the protective effect of BNP. Collectively, BNP offers a novel choice to mitigate PE-induced pulmonary vasoconstriction via NPRC-mediated mechanisms, which support BNP's therapeutic potential for intermediate-high-risk PE.

The dual role of formyl peptide receptor 1 (FPR1) in gastrointestinal inflammation and carcinogenesis: mechanisms and therapeutic implications.

Atogepant is an oral calcitonin gene-related peptide receptor antagonist approved in the USA, EU, and Japan for the preventive treatment of migraine in adults. We evaluated the long-term safety, efficacy, and functional outcomes of atogepant for the preventive treatment of migraine in Japanese participants. This open-label, 52-week, long-term safety extension study evaluated atogepant 60mg once daily for the preventive treatment of migraine in Japanese participants. The study enrolled participants with chronic migraine (CM) who completed the phase3 PROGRESS trial and de novo participants with episodic migraine (EM). The primary objective was the safety and tolerability of atogepant. Efficacy and functional outcomes were exploratory endpoints. Of 204 Japanese participants screened, 186 were enrolled and included in the safety population (CM, n = 155; EM, n = 31) and 180 in the modified intent-to-treat population (CM, n = 150; EM, n = 30). Treatment-emergent adverse events (TEAEs) occurred in 88.7% of participants. TEAEs occurring ≥ 10% were pyrexia (29.0%), nasopharyngitis (16.1%), and constipation (11.3%). Concurrent COVID-19 vaccination attributed to several TEAEs, including pyrexia. Serious TEAEs occurred in 3.8% of participants and none were considered related to atogepant by the investigator. TEAEs leading to discontinuation occurred in 4.8% of participants. Alanine aminotransferase and/or aspartate aminotransferase ≥ 3 × the upper limit of normal occurred in 4.8% of participants; none met criteria for Hy's law. The least squares mean change from baseline in monthly migraine days was - 6.4days in PROGRESS CM completers and - 3.4days in de novo EM participants at weeks1-4 and was consistent over 52weeks. Similar improvements were observed for the other efficacy and functional outcomes. The safety profile of atogepant in Japanese participants was consistent with the known safety profile in the global population. No new safety signals were identified. Improvements in efficacy and functional outcomes persisted over 52weeks. NCT04437433; https://clinicaltrials.gov/study/NCT04437433.

Bladder pain significantly impacts millions worldwide, severely affecting their quality of life and posing a major clinical challenge. Understanding the mechanisms underlying persistent bladder pain is critical for developing better therapeutic strategies. In this study, we investigate the effects of cyclophosphamide (CYP)-induced persistent bladder sensitization to explore the lateralized contribution of amygdala calcitonin gene-related peptide receptors (CGRP-Rs) on pain-like changes in mice. We demonstrate that CYP induces hypersensitivity lasting up to 14 days postinjury (DPI) in the urinary bladder distention assay and up to 21 DPI when assessing abdominal mechanical sensitivity. Despite persistent pain-like changes, no significant bladder histological changes were observed. Based on previous findings that CGRP signaling from the parabrachial nucleus contributes to central amygdala (CeA) lateralization, we hypothesized that CGRP-Rs play a key role in driving visceral bladder pain-related hemispherical differences. We show that inhibiting CGRP-R activity with the antagonist CGRP 8-37, in the right CeA attenuates bladder pain-like behavior, whereas left CeA inhibition sustains CYP-induced hypersensitivity. Electrophysiological recordings revealed increased firing frequency in CGRP-R-positive cells in the right CeA 7 DPI. In vivo single photon calcium imaging demonstrated increased Ca transients in CGRP-R-positive cells in the right CeA, upon the presentation of a stimulus at 0 DPI and overall at 2 DPI, further confirming the pronociceptive role of CGRP-Rs in the right CeA. Taken together, these findings provide a crucial foundation for understanding pain-induced CeA lateralization and for further studies identifying how targeting CGRP signaling could provide bladder pain relief.

Trifolirhizin alleviates bone destruction in rheumatoid arthritis by inhibiting osteoclast differentiation through the activation of FPR2.

Atogepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for migraine prevention; however, real-world data from the Middle East and North Africa (MENA) region remain limited. This study evaluated the efficacy and safety of atogepant in patients with chronic and episodic migraine in the United Arab Emirates. This retrospective study included adult patients (≥ 18years) diagnosed with chronic or episodic migraine who received atogepant for at least 6months. Clinical data were extracted from electronic medical records at the American Center for Psychiatry and Neurology, Abu Dhabi. Monthly migraine days (MMD) at baseline were compared with follow-up MMD documented at visits occurring at least every 2months. Safety outcomes were assessed through descriptive analysis of reported adverse events (AEs) in the all-exposed population. Sensitivity analyses (non-responder imputation, baseline observation carried forward, multiple imputation under MAR, and tipping point analysis) were conducted to evaluate the robustness of efficacy results in the presence of missing data. Of 86 patients identified, 59 met the inclusion criteria and their data were analyzed. Among these, 39% had chronic migraine and 61% had episodic migraine. The majority were female patients (86.4%) and Emirati nationals (69%). The mean baseline MMD was 12 (SD 8.1), which decreased to 4 (SD 5.2) at the most recent follow-up. Overall, 71% achieved ≥ 50% reduction in MMD, 20% achieved < 50% reduction, and 9% experienced no change. Paired-sample ttest demonstrated a significant reduction in MMD t(58) = 9.44, p < 0.001. Adverse events were reported in 10.5% (9/86) of patients, most commonly constipation and nausea. Most patients experiencing AEs (78%) continued treatment, while two discontinued. In this real-world cohort from the UAE, atogepant was associated with significant reductions in monthly migraine days in both patients with chronic and episodic migraine and demonstrated a favorable safety and tolerability profile.

Photoageing, a major form of extrinsic skin ageing, primarily results from chronic ultraviolet (UV) irradiation. Although accumulating evidence implicates tRNA-derived small RNAs (tsRNAs) in ageing, inflammation and oxidative stress, their precise roles in photoageing remain insufficiently defined. To investigate the function of tRNA-derived fragment (tRF)-34 in photoageing and to define the underlying molecular mechanism. tRF-34 expression was evaluated in UVA1-irradiated primary human dermal fibroblasts (HDFs), murine skin and sun-exposed human skin, using reverse transcription quantitative polymerase chain reaction and fluorescence in situ hybridization. Functional characterization was performed with tRF-34 overexpression and knockdown. Downstream mechanisms were elucidated mainly using RNA sequencing, RNA pulldown, RNA immunoprecipitation and m⁶A methylation analysis. tRF-34 was significantly downregulated in photoaged HDFs. Restoration of tRF-34 ameliorated photoageing in HDFs, while its inhibition exacerbated senescence-related features. Mechanistically, tRF-34 bound to YTH domain family protein 2 (YTHDF2), inhibiting YTHDF2-mediated m⁶A-dependent degradation of NPR3 mRNA. Natriuretic peptide receptor C (NPRC), also diminished in photoageing, exerted photoprotective effects through activation of transforming growth factor-β1/SMAD signalling. In vivo, tRF-34 overexpression mitigated chronic UVA1-induced wrinkle formation and improved collagen content in photoaged mice. Our work establishes a novel tRF-34/YTHDF2/NPRC regulatory axis that preserves skin homeostasis against chronic UV damage, providing new mechanistic insights and suggesting a potential basis for future translational exploration in photoageing.

SSTR-PET is routinely used to select patients with neuroendocrine neoplasms (NEN) for peptide receptor radionuclide therapy (PRRT). As the kidneys are organs at risk, this study evaluated whether renal uptake on pre-therapeutic SSTR-PET/CT reflects split or global renal function and correlates with renal absorbed dose during [177Lu]Lu-DOTA-TATE therapy. In this retrospective study, 85 NEN patients treated with [177Lu]Lu-DOTA-TATE between 2013 and 2023 were included. All underwent SSTR-PET/CT using [18F]SiTATE, [68Ga]Ga-DOTA-TATE, or [68Ga]Ga-DOTA-TOC plus serum kidney function tests and [99mTc]Tc-MAG3 scintigraphy. Renal PET uptake was compared with serum and scintigraphic kidney parameters. In 30 patients, renal absorbed dose was estimated using post-treatment SPECT/CT. Renal uptake on SSTR-PET/CT moderately correlated with split renal function assessed by [99mTc]Tc-MAG3 across all tracers, particularly using SUVmean ([18F]SiTATE (r = 0.462; p = 0.010); [68Ga]Ga-DOTA-TATE (r = 0.515; p = 0.004); [68Ga]Ga-DOTA-TOC (r = 0.546; p = 0.004)). No relevant correlation was observed between total renal PET uptake and tubular extraction rate, eGFR, or serum creatinine. Renal PET uptake showed moderate correlations with mean absorbed doses in selected tracer cohorts ([18F]SiTATE; r = 0.585; p = 0.076; [68Ga]Ga-DOTA-TATE; r = 0.649; p = 0.049). A strong negative correlation between TER and absorbed dose was seen only for [18F]SiTATE (r = - 0.768; p = 0.010). SSTR-PET/CT showed moderate potential to estimate pre-therapeutic split renal function and renal absorbed dose. However, global renal function could not be reliably estimated using PET/CT. Larger studies are warranted to validate PET/CT-based kidney assessment for individualized PRRT planning.

Excess visceral abdominal fat (EVAF) is a prevalent metabolic complication among people living with HIV-1 (PLWH), occurring even in individuals with normal or mildly elevated body mass index (BMI). This pattern of fat accumulation is associated with metabolic dysfunction, cardiovascular risk, and reduced quality of life. Since EVAF can present without generalized obesity, weight-based assessments may fail to identify it; moreover, addressing EVAF warrants distinct approaches based on a patient's presentation. Two therapeutic classes have been studied in this setting: growth hormone-releasing hormone analog (tesamorelin), which selectively reduces visceral fat, and glucagon-like peptide (GLP-1) receptor agonists, which induces generalized weight loss in a nonspecific way. Two adults with well-controlled HIV presented with central adiposity. The first patient demonstrated a nonobese visceral adiposity phenotype characterized by increased waist circumference (WC) and a BMI of 27 kg/m². Treatment with tesamorelin led to marked reductions in WC, improved lipid levels, and enhanced functional well-being. The second patient, a woman with higher BMI representative of obesity, received a GLP-1; however, her intermittent access to the medication resulted in fluctuating weight trends and persistent abdominal fat. Incorporation of tesamorelin provided a more targeted approach to reduce visceral adiposity in this context. Both cases demonstrated that EVAF may persist independent of BMI category and may respond differently to therapies targeting generalized obesity versus selective visceral abdominal fat. These cases highlight the heterogeneity of EVAF in PLWH and support individualized management strategies informed by fat distribution rather than weight alone.

Migraine is a disabling neurological disorder with limited tolerability and cardiovascular limitations associated with traditional acute therapies such as triptans. Rimegepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist, has emerged as a promising treatment option. This meta-analysis evaluated the efficacy and safety of a single 75mg oral dose of rimegepant for acute preventive treatment of migraine. A systematic search of PubMed, Scopus, and Web of Science was conducted from inception to October 2025. Only randomized controlled trials (RCTs) evaluating oral rimegepant 75 mg for acute migraine in adults were included. Primary outcomes included pain freedom and pain relief at 2, 24, and 48h. Secondary outcomes included freedom from associated migraine symptoms, return to normal function, rescue medication use, and adverse events. A random-effects model was applied for pooled analysis. Nine RCTs involving 7,198 participants were included. Participants received a single 75mg oral dose of rimegepant per migraine attack. Rimegepant demonstrated significantly greater 2-hour pain freedom compared with placebo (RR = 1.77; 95% CI: 1.5-2.1). Two-hour pain relief was similarly improved (RR = 1.35; 95% CI: 1.28-1.42). Safety outcomes were comparable to placebo, with no significant differences in total adverse events (RR = 1.10) or serious adverse events. A single 75mg oral dose of rimegepant is an effective and well-tolerated therapeutic option for both acute and preventive migraine treatment, offering meaningful clinical improvement and a favorable safety profile. Its non-vasoconstrictive mechanism provides a valuable alternative for patients unable to use triptans or those who respond inadequately to existing therapies.

Functional divergence of NPR1 paralog in the Japanese eel: Identification and neuroanatomical characterization.

A neutral polysaccharide from the pulp of Trichosanthes kirilowii Maxim mitigates constipation through microbiota-dependent activation of brain-gut axis.

Oxidative stress and inflammation are two closely related pathogenesis processes during ischemic injury. The current study investigated the neuroprotective effects of resolvin D1 (RvD1, a pro-resolving mediator) and its corresponding receptor formyl peptide receptor 2 (FPR2) in a rat model of middle cerebral artery occlusion (MCAO). Dynamic expressions of endogenous RvD1 and FPR2 in ischemic hemisphere were firstly examined by ELISA and western blot respectively. To explore the therapeutic effects of RvD1/FPR2 on ischemic injury, exogenous RvD1 were given at 0.4µg/kg after MCAO (i.p.). Boc-2 (specific FPR2 antagonist to inhibit effects of RvD1/FPR2) were administered at 0.4mg/kg (i.p.) 30min before MCAO to inhibit the binding of RvD1 to FPR2. For evaluating ischemic injury, neurological performances were determined by deficit score and grip strength, and infarction volume were assayed by TTC. Neuronal damage was further observed by stainings of H&E, Fluoro-Jade C (FJC), and TUNEL. Inflammation markers were assayed by MPO immunostaining and mRNA dectection. Oxidative stress was determined by related kits (MDA, NO, GSH and SOD) and MitoSOX staining. Our results showed that endogenous cerebral levels of RvD1 were decreased after focal ischemia, but expression of FPR2 was increased. Exogenous RvD1 treatment alleviated neurological deficits, reduced infarct volume and attenuated neuronal apoptosis, however, inhibition of FPR2 by Boc-2 inhibited these effects. Furthermore, RvD1 reduced MPO positive cells and mRNA levels of pro-inflammatory mediators (TNF-α, IL-1β, and iNOS), but increased mRNA levels of anti-inflammatory mediators (TGF-β1 and IL-10). Concurrently, RvD1 inhibited oxidative stress, evidenced by down-regulated pro-oxidative mediators (such as MDA and NO) and up-regulated anti-oxidative mediators (SOD and GSH). Boc-2 alleviated the anti-inflammatory and anti-oxidant effects of RvD1. Mechanistically, RvD1 decreased expression of NOX2 in microglia and astrocytes, while co-administration of Boc-2 reversed these effects. These finding demonstrate that RvD1/FPR2 alleviated cerebral ischemic injury by attenuating inflammation and oxidative stress, which is beneficial to break the vicious cycle between inflammation and oxidative stress, thus highlighting its potential role in treatment for ischemic stroke.

Nuclear medicine has revolutionized diagnostic and therapeutic strategies in oncology by offering molecular-level insights into tissue function-often detecting pathological changes before they manifest structurally. At the heart of this advancement lies the growing field of radiotheranostics, which combines targeted molecular imaging with precision radiotherapy. One of the most promising molecular targets in this field is the Gastrin-Releasing Peptide Receptor (GRPR), which is overexpressed in several solid tumors, including prostate cancer, breast cancer, and Gastrointestinal Stromal Tumors (GISTs). Among the GRPR-targeting radiopharmaceuticals, NeoB (formerly NeoBOMB1)-a radiolabeled GRPR antagonist-has emerged as a potent agent, enabling both diagnostic imaging ([67/68Ga]Ga-NeoB) and targeted radionuclide therapy ([177Lu] Lu-NeoB). This narrative review examines the current state of NeoB-based radiopharmaceuticals in cancer, with a focus on their diagnostic and therapeutic applications, primarily in prostate cancer, breast cancer, and Gastrointestinal Stromal Tumors (GIST), including preclinical and clinical studies published up to January 2025. Additionally, limitations and future directions are addressed. In diagnostic imaging, [68Ga]Ga-NeoB PET/CT demonstrated high detection rates for primary tumors and distant metastases in GRPR-positive cancers, with moderate accuracy for detecting lymph node metastases. In therapeutic studies, [177Lu] Lu-NeoB showed strong tumor uptake and significant antitumor activity in preclinical models, with no observed toxicity. One ongoing multicenter clinical trial, initiated in 2019, is assessing the safety and efficacy of [177Lu] Lu-NeoB in patients with advanced or metastatic cancers, including those with moderate renal impairment. Despite encouraging findings, several limitations remain. GRPR is physiologically expressed in normal tissues such as the pancreas and kidneys, leading to non-specific uptake and potential off-target radiation. Optimizing molecular structure, radionuclide selection, and dosing strategies is essential to reduce toxicity. Moreover, long-term efficacy and safety data in humans are still lacking, and further largescale clinical trials are needed to validate NeoB's clinical utility.

177Lu]Lu-DOTATATE PRRT and CAPTEM chemotherapy for pancreas and small bowel neuroendocrine tumours: The AGITG CONTROL NETS Multi-centre randomized trial.

N-terminal (Nt) methionine formylation, once thought restricted to bacteria and organelles, is now recognized as a stress-inducible initiator modification in the eukaryotic cytosol. Under metabolic or environmental stress, mitochondrial methionyl-transfer RNA (tRNA) formyltransferase mislocalizes to the cytosol, generating formylated initiator tRNA (fMet-tRNAi) that initiates translation with N-formylmethionine (fMet). Nascent chains bearing Nt-fMet activate an fMet-directed ribosome-associated quality control checkpoint early in elongation, recruiting ribosome-splitting and disaggregation factors. Stalled complexes are routed to stress granules, conserving mRNA, translation machinery, and energy, while limiting aggregation. During prolonged stress, newly synthesized fMet proteins undergo maturation or selective degradation via the fMet/N-degron pathway. In mammals, E3 ligase TRIM52 acts as an Nt-fMet recognin, modulating apoptosis. Proteolytic clearance of cytosolic fMet substrates releases formylated peptides and free fMet, which are elevated in critical illness and activate formyl peptide receptors - linking translation surveillance to innate immune and inflammatory signaling in sepsis and age-related disease. Advances in N-terminomics and anti-fMet reagents now allow direct detection and quantification of cytosolic fMet proteoforms. This Review integrates bacterial and organellar paradigms with emerging cytosolic mechanisms, examines regulatory gating of Nt-formylation, and highlights therapeutic strategies to restore proteostasis and counter fMet-associated pathology.

Egg yolk oil promotes deep second-degree burn healing via multiple regulation and Annexin A1-Formyl peptide receptor 2 axis activation.

In this prospective study, we aimed to investigate the factors associated with somatostatin receptor (SSTR) expression in patients with recurrent or metastatic differentiated thyroid cancer (DTC). Patients with DTC scheduled for 131I therapy at the study institution were enrolled. The inclusion criteria required at least one assessable lesion (≥ 1 cm). SSTR expression was assessed by 111In-pentetreotide single-photon emission computed tomography/computed tomography (SPECT/CT), with Krenning scores of ≥ 2 considered positive. Fluorodeoxyglucose positron emission tomography (FDG PET) and post-131I therapy SPECT/CT were also evaluated. Quantitative evaluation was performed using standardized uptake values (SUV). Clinical factors were compared between SSTR-positive and SSTR-negative patients. Spearman’s correlation coefficient was calculated to evaluate the relationship between lesion size and SUVmax from 111In-pentetreotide SPECT, FDG PET, and 131I SPECT. Generalized estimating equations (GEEs) were utilized to identify predictors of SSTR positivity, accounting for within-patient correlation among multiple lesions. Furthermore, receiver operating characteristic (ROC) curves with clustered bootstrap resampling were used for evaluating the diagnostic performance of significant predictors. Fourteen patients with DTC (six male; median age, 70.5 years) were evaluated, and 31 lesions were assessed. High SSTR expression was observed in 28.6% (4/14) of patients and 51.6% (16/31) of lesions. SSTR positivity was associated with follicular histology, elevated thyroglobulin (Tg) levels, 131I uptake, larger lesion size, and bone metastasis. Using GEEs accounting for intra-patient clustering, higher 131I SUVmax was the strongest independent predictor of SSTR positivity (p < 0.001). ROC analysis demonstrated 131I SUVmax yielded a high area under the curve of 0.93 (95% confidence interval: 0.65–1.00) for predicting SSTR positivity. SSTR SUVmax positively correlated with lesion size (ρ = 0.67), and 131I SUVmax (ρ = 0.73). Although 18F-FDG SUVmax moderately positively correlated with SSTR SUVmax (ρ = 0.49), it was not an independent predictor of SSTR positivity in GEE (p = 0.163). In this first study, high SSTR expression in Japanese patients with DTC was evaluated, demonstrating patients with follicular thyroid carcinoma, elevated Tg levels, larger tumor size, and positive 131I uptake are more likely to have SSTR-positive lesions. These findings might support the development of novel SSTR-targeted radiopharmaceutical therapies for DTC.

Positron emission tomography (PET) has become an increasingly important adjunct to brain MRI in the field of neuro-oncology. PET imaging utilizes radiolabeled tracers, providing in vivo assessment of the metabolic and molecular characteristics of gliomas, thereby providing functional data beyond standard anatomic images. This additional layer of crucial biological insight aids in personalized patient management and treatment decision. In recent years, numerous studies have been carried out for the development and clinical validation of several PET radiotracers in glioma imaging, leading to a substantial improvement in glioma diagnosis, staging, treatment strategy planning as well as in monitoring tumor progression and response to therapy. Ongoing innovations in radiopharmaceutical design have further improved the diagnostic performance of PET by increasing both tracer specificity and tumor detection sensitivity. In this review, we summarize recent developments in PET imaging for glioma, with particular emphasis on clinically available amino acid PET tracers. In addition, we provide an overview of emerging theranostic strategies, including peptide receptor radionuclide therapy (PRRT) for meningioma and 177Lu-PSMA-617-based approaches for high-grade glioma. The current guidelines recommend the use of amino acid PET for differentiation of neoplastic from non-neoplastic lesions, for delineation of glioma extent, for non-invasive prediction of molecular information, for grading and prognosis estimation, for differentiation of glioma relapse from treatment-related changes and for the evaluation of treatment response. Overall, this work aims to highlight the role of PET as a complementary imaging modality to MRI and to discuss its potential impact on patient outcomes in neuro-oncological practice.

Sclerostin (SOST) is a key negative regulator of bone formation and an emerging biomarker associated not only with osteoporosis but also with chronic kidney disease. Despite its growing clinical relevance, biosensing platforms for SOST remain limited, with most existing approaches relying on antibody- or aptamer-based assays that often suffer from high cost, limited stability, and reduced performance in complex biological samples. Here, we report a peptide-based electrochemical biosensing platform enabled by a multifunctional zwitterionic biopolymeric nanohydrogel, composed of chitosan, carboxybetaine methacrylate, and gold nanoparticles (CS-ZI-AuNPs). This nanohydrogel acts as a unified antifouling biointerface, simultaneously providing resistance to nonspecific adsorption, stable peptide receptor immobilization, and efficient electrochemical signal transduction. The resulting biosensor achieves picomolar sensitivity with a detection limit of approximately 26.4 pg/mL, enabling accurate quantification of SOST across clinically relevant concentration ranges. Importantly, the platform demonstrates statistically significant discrimination between healthy individuals and patients with osteoporosis, postmenopausal osteoporosis, and chronic kidney disease (stages 1 and 3) using real clinical samples. By integrating zwitterionic antifouling chemistry with peptide-driven molecular recognition in a conductive nanostructured matrix, this work establishes a generalizable design principle for electrochemical biosensors targeting protein biomarkers. The proposed strategy offers a robust and scalable alternative to conventional immunoassays, with broad implications for translational diagnostics and real-time disease monitoring.