Host-guest confinement in post-metallized COFs for enhanced electrochemiluminescence coupled with Y-shaped DNA amplification for microRNA-499 detection.

Mechanistic insights into persulfate-driven electrochemiluminescence amplification enabled by a Ru@Cu-MOGs/Zr-CeO2-Ag hybrid system.

A ratiometric fluorescent probe based on FRET mechanism for the detection of SO₃2-/HSO₃.

Ischemic stroke, the second leading cause of death and a primary source of severe disability in adults worldwide, is associated with high morbidity and mortality rates that correlate closely with the extent of neuronal damage. A critical strategy for improving patient outcomes is the early identification and rescue of the ischemic penumbra, a region at risk but potentially salvageable. However, accurately identifying and visualizing this penumbra poses a significant challenge in treatment and is crucial for predicting patient prognosis. Conventional magnetic resonance imaging (MRI) techniques often fail to delineate viable tissue effectively.Cleaved Caspase-3 (c-Casp3), a key executor of apoptosis, is specifically and highly expressed within the penumbra, making it an ideal molecular target for precise imaging. To address this challenge, we designed and constructed a multifunctional, enzyme-responsive MRI nanoprobe (FGAPT) for the molecular imaging of the ischemic penumbra. This probe capitalizes on the elevated expression of activated Caspase-3 during ischemic neuronal apoptosis, facilitating its specific accumulation and activation at the lesion site. As a result, there is a significant enhancement of the T1-weighted imaging signal, allowing for accurate delineation of the penumbra. This study establishes an imaging strategy for the precise identification of the ischemic penumbra, thereby presenting a paradigm for guiding individualized thrombolytic and neuroprotective interventions in ischemic stroke. The proposed methodology lays a robust imaging foundation for transitioning stroke management from a generalized therapeutic approach to personalized treatment optimization. STATEMENT OF SIGNIFICANCE: The precise delineation of the ischemic penumbra is critical for guiding therapy in acute ischemic stroke, yet remains a challenge for conventional imaging. To address this, we developed an enzyme-responsive magnetic resonance imaging (MRI) nanoprobe, FGAPT, for the molecular visualization of this salvageable tissue. This smart probe is engineered around a MRET mechanism, linking a superparamagnetic quencher (Fe₃O₄) and a paramagnetic enhancer (Gd-DOTA) with a peptide sequence specifically cleaved by activated Caspase-3-a key executor of apoptosis upregulated in the penumbra. Surface conjugation of a brain-targeting aptamer ensures blood-brain barrier penetration. In a rodent stroke model, the probe achieved high-contrast, specific T1-signal enhancement exclusively within the penumbra, as confirmed by spatial colocalization with histologically verified apoptotic cells. This Caspase-3-activated imaging strategy enables accurate differentiation between the infarct core and the ischemic penumbra. By directly visualizing a pivotal molecular determinant of cellular fate, our work provides a novel tool to advance stroke management from a rigid "time window" paradigm toward a precision "tissue window" approach.

The potential to mitigate pain by targeting a single receptor while simultaneously modulating peripheral and spinal circuits, offers an exciting nonopioid therapeutic strategy. Neurotensin receptor type 2 (NTSR2) is a promising yet underexplored pathway for nonopioid analgesia. The authors investigated the antinociceptive effects of NTSR2 activation and its mechanisms in rodent models of perioperative and chronic pain. Using NT79, a selective NTSR2 agonist, the authors assessed pain behaviors in male and female rats and mice. Animals were randomly assigned to receive saline (control) or NT79 at multiple doses. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated NTSR2 knockdown and pharmacologic inhibition of γ-aminobutyric acid (GABA) receptors were used to dissect NTSR2-dependent mechanisms. Dorsal root ganglion (DRG) calcium imaging, whole cell patch clamp electrophysiology, and spinal neurotransmitter assays evaluated the modulation of voltage-gated calcium channels and γ-aminobutyric acid-mediated (GABAergic) signaling. Intrathecal NT79 produced robust, dose-dependent antinociception across pain models, species, and sexes, an effect abolished by NTSR2 knockdown. NT79 reduced high-voltage-activated calcium currents in DRG neurons, indicating a presynaptic inhibitory mechanism. In the spinal cord, NT79 enhanced GABA release and suppressed calcitonin gene-related peptide (CGRP) release. Pharmacologic blockade of GABA receptors partially reversed NT79's antinociceptive effects, as did NTSR2 knockdown in GABAergic neurons, supporting a central GABAergic mechanism in addition to the effect on central DRG terminals. Taken together, these results demonstrate that NTSR2 activation produces sustained antinociception via dual-site modulation: inhibition of peripheral voltage-gated calcium channels and enhancement of spinal GABAergic signaling. These findings identify a novel, nonopioid mechanism of analgesia and support NTSR2 as a therapeutic target for chronic pain.

Mitochondrial fusion targeted supramolecular peptide hydrogel for gut neuroprotection.

This work presents the performance of a semi-open electrochemical cell (SOEC) for potentiometric biosensing. In this design, the electrodes are vertically stacked, and a solid-state polyelectrolyte is used as separator. This paper-based device requires a minimal sample volume, as only the top working electrode contacts the solution while the reference electrode remains shielded in the bottom of the cell. Using a paper-based Pt working electrode, the system demonstrates high sensitivity to hydrogen peroxide with linear response below 10 µM and a Tafel slope of 120 mV/decade at higher concentrations. Electrode area optimization enables tunable analytical performance by controlling sensitivity and linear ranges. The device exhibits exceptional stability, with a baseline noise level below 0.1 mV and low impedance, facilitating integration with simple operational amplifiers. This design achieves ultralow detection limits for hydrogen peroxide (~10 nM) using only 1 µL sample volumes and maintains linearity up to 10 mM. When coupled with oxidase enzymes, the system enables rapid and versatile glucose testing in artificial serum and sweat using single sample drops, with absolute limits of detection in the µM range. This compact, versatile paper-based platform offers promising opportunities for developing wearable, disposable biosensors for point-of-need applications. • Vertically-stacked electrochemical sensor with exceptional stability and broad range of detection • Tunable analytical performance through electrode area optimization • 10-fold signal enhancement via non-inverting operational amplifier integration • Nanomolar detection limits in single-microliter samples • Reliable glucose quantification in artificial serum and sweat from single drops

CIGAN: rehabilitation-oriented few-shot speech separation for cocktail party problem in Cochlear implant users

Multi-pulse laser-induced breakdown spectroscopy signal enhancement using a MHz-repetition-rate pulsed fiber laser source

Benchtop NMR spectroscopy is an affordable and accessible technique for mixture analysis but suffers from lower sensitivity and increased signal overlap compared to standard high-field NMR. Signal amplification by reversible exchange (SABRE) hyperpolarization can effectively address the sensitivity limitation, with automation of the hyperpolarization step enabling the multistep NMR experiments required to resolve signal overlap for complex mixture analysis. The automated workflow presented herein delivers highly repeatable hyperpolarization (with a 2.5% relative standard deviation in signal enhancement across 100 experiments) and can be integrated into any NMR pulse sequence with typical repolarization times of ∼13 s. Using this approach, a fully resolved 13C{1H} benchtop NMR spectrum with signal-to-noise ratios of up to 40 for a mixture of pyridine, 4-methylpyridine, and 3,5-dimethylpyridine (3 mM each) at natural isotopic abundance is obtained with only 18 min of signal averaging. Overlapped peaks in the 1H NMR spectrum of this mixture are resolved using a SABRE-enhanced 2D 13C-1H HETCOR experiment (8 scans, 2.4 h). Analysis of a lower concentration mixture (750 μM per analyte) is exemplified with a SABRE-enhanced 2D 1H-1H COSY spectrum acquired in a single scan in 37 min.

Beyond traditional SERS: Integrating pH control and renewable screen-printed electrode for EC-SERS detection.

Lateral flow immunochromatographic assay (LFIA) is a classic point-of-care testing technique. However, its sensitivity is commonly constrained by the signal intensity of conventional probes, restricting the detection of low-abundance biomarkers. Herein, we report an ultrasensitive LFIA platform based on coordination/assembly-regulated signal programming enabled by metal-organic frameworks (MOFs), termed Coordination/Assembly Twin-Boosted LFIA (CATB-LFIA). Zeolitic imidazolate framework-8 (ZIF-8) is employed as the core bifunctional scaffold. Based on a novel coordination-driven signal enhancement strategy, the exposed Zn2+ sites within the ZIF-8 framework act as active centers to trigger coordination reactions with zinc indicators under mild conditions, enabling rapid generation and localized deposition of chromogenic products. Meanwhile, the confinement effect of ZIF-8 allows high-density loading of gold nanoparticles, further enhancing the colorimetric signal intensity of probes. Using carcinoembryonic antigen as model targets, CATB-LFIA achieved a 25-50-fold reduction in the limit of detection compared to conventional LFIA. In clinical serum samples, CATB-LFIA demonstrated accurate quantitative capability with good discriminatory performance. Overall, this work demonstrates the advantages of MOFs as multifunctional carriers in LFIA, providing a novel design for constructing sensitive and modular diagnostic platforms.

While ambient mass spectrometry imaging (MSI) is essential for biological analysis, its sensitivity remains constrained by ion transmission losses due to collisions and gas dynamics. Here, a high-performance desorption electrospray ionization (DESI) MSI system featuring a high-efficiency dual-stage ion funnel (DIF) was developed. To optimize the system configuration, a hybrid multiphysics simulation model was constructed by coupling gas dynamics, electric field, and ion transport simulations. The simulation model was validated against experimental data from mouse brain homogenates, confirming its accuracy in predicting ion transport behavior under realistic conditions. With the optimized DIF assembly, signal enhancements of up to 490-fold and the detection of 303 additional mass peaks in mouse brain sections were achieved compared to the standard S-lens interface. Furthermore, post-photoionization (PI) was introduced to expand molecular coverage to non-polar compounds and simultaneously enhance sensitivity. Overall, this study provides theoretical insights into ion motion within complex coupled fields and offers guidelines for the design of high-sensitivity ambient MSI interfaces.

A miR-382-5p-PORCN axis modulates endogenous Wnt signaling during palatal development.

As biosafety requirements continue to increase, there is a growing interest in foodborne-pathogen detection methods that can be operated safely. In this work, a dual-functional "sterilization-detection" photoelectrochemical (PEC) biosensing platform is developed based on a Fe3O4/copper-benzene-1,3,5-tricarboxylic acid (Cu-BTC), which integrates efficient photothermal sterilization with excellent photoelectric performance. The aptamer-modified magnetic substrate is employed to specifically capture and magnetically separate Escherichia coli O157:H7, inducing a steric hindrance effect that decreases the photocurrent. Upon near-infrared irradiation, the composite exhibits a strong photothermal response, enabling efficient in situ sterilization of the captured bacteria. Subsequently, the lipopolysaccharides (LPS) released during bacterial lysis are adsorbed onto the Fe3O4/Cu-BTC surface via Cu-O-P bonds. The phosphate groups in LPS coordinate with Cu2+, passivating surface defects and suppressing nonradiative recombination, thereby prolonging carrier lifetime and boosting the photocurrent. The resulting ratiometric PEC sensing platform shows a linear range of 2.2 × 102-2.2 × 106 CFU/mL with detection limit as low as 41 CFU/mL. Thus, this work not only achieves the enhancement of PEC signals through in situ adsorption of LPS but also proposes an integrated strategy for the simultaneous inactivation and accurate quantification of foodborne pathogens. It demonstrates promising potential for on-site food safety monitoring and proactive biosafety control.

A parallel heterodyne light-induced thermoelastic spectroscopy (PH-LITES) sensor is proposed for high-speed and high-sensitivity multi-gas detection for the first time. Within the collaborative signal enhancement architecture (CSEA), high sensitivity and high-speed detection are achieved at the physical layer. A self-designed cylindrical multi-pass cell (MPC) with a recorded high optical path length to volume ratio (OPL/V = 37.4 cm-2) and a four‑tine quartz tuning fork (QTF) with a low resonant frequency (f0 = ~7.9 kHz) work synergistically to enhance detection responsivity, establishing a robust foundation for highly sensitive detection of low-concentration gas mixtures. High‑speed capability is enabled by parallel heterodyne modulation, where a single QTF is excited to generate a composite transient response signal, allowing for the rapid, simultaneous acquisition of spectral information from multiple gases. At the information layer, intelligent processing is implemented via a collaborative intelligent processing architecture (CIPA) integrating convolutional neural networks (CNN), a hybrid attention mechanism (HAM), and bidirectional long short-term memory (BiLSTM). The CNN-HAM-BiLSTM architecture performs feature extraction, attention-based enhancement, and temporal modeling to enable accurate concentration retrieval from the parallel spectra derived from a single QTF output. Experimental validation using methane (CH4) and acetylene (C2H2) achieved minimum detection limits (MDLs) of 378 ppb and 285 ppb, respectively, within a 4 s scanning time. The proposed system offers an efficient solution for applications requiring rapid and sensitive multi-gas detection.

Performance optimization of AlN protected layer SAW high-temperature sensors and research on wireless signal enhancement technology for devices

Chemiluminescence (CL) offers excitation-free optical readout with minimal background signal, making it highly attractive for diagnostics and imaging. However, most reported 1,2-dioxetane-based chemiluminophores exhibit long-lasting CL but low instantaneous intensity, limiting their imaging applications. Here, we report a series of burst-mode near-infrared (NIR) chemiluminophores with high instantaneous brightness via a substituent-driven electronic-tuning approach to reduce the activation barrier of bond scission within chemiluminophores. After replacing the 3-methoxy group of 1,2-dioxetane in the dicyanomethylene-phenoxy-dioxetane (DPD) with different substituents, the 2,2,2-trifluoroethyloxy-modified analogue DPD4 is identified to show the activation barrier energy required for the transition state of O-O dissociation, approximately 3-fold lower than that of the methoxy-substituted DPD1. This reduction corresponds to a 15.0-fold increase in the relative chemiexcitation rate versus DPD1. Consequently, DPD4 displays pronounced burst-mode NIR emission, featuring a remarkable ∼79,978-fold intensity enhancement and a markedly shortened CL half-life (t1/2,CL = 10 s) while retaining ultrahigh chemical stability with a half-life of 6.8 days in buffer at room temperature. Then, the optimized chemiluminophore DPD4 is constructed into an activatable probe DPD4g to selectively trigger its strong CL responses by β-galactosidase (β-gal) in live cells. In vivo, DPD4g distinguishes β-gal-overexpressing tumors, affording a 15.2-fold signal enhancement relative to β-gal-negative tumors. This work establishes trifluoroethyl substitution as a generic route to construct burst-mode chemiluminophores for sensitive CL molecular imaging in living systems.

Abstract Background Pediatric bithalamic gliomas (pBTG) are rare subsets of thalamic tumors with clinical and biological heterogeneity. Limited comprehensive data are available. Methods We retrospectively assembled a multi-institutional cohort of children diagnosed with pBTG between 2002-2023, to describe their clinical, radiological, pathology, molecular characteristics, management and outcome. Results Forty-three patients (26 males) were included; median age at diagnosis was 7 years(range 0.2-18). Median symptom duration at presentation for low- grade glioma(pLGG) and high-grade glioma(pHGG) were 12(range 2-104) and 7.5 weeks(range 1-43). pLGG and pHGG accounted for 44% and 56%. Molecular data were available in 53% pLGG and 67% pHGG. In pLGG, alterations included BRAFV600E (21%), BRAF fusion(5%), other BRAF mutation(5%) and FGFR1 mutation(5%). In pHGG, molecular alterations included TP53(38%), H3K27(33%), EGFR exon 20(21%), BRAF V600E(4%) and ATRX(4%). At diagnosis, extension beyond the thalamus was present in 98% with asymmetrical involvement in 70%. Restricted diffusion, enhancement and internal areas of low-T2 signal predicted pHGG. Following surgery, 9% were observed while 81% received adjuvant therapy. Chemotherapy was used upfront in 47%, targeted therapy in 5% of pLGG, versus 63% and 4% in pHGG patients. Twenty-one patients (49%) underwent upfront radiotherapy (11% pLGG, 83% pHGG), median dose 54Gy. Median progression time was 15 months(range 1-100) and 7 months(range 1-17) for pLGG and pHGG. After first relapse, pLGG patients underwent median of 2 lines of chemotherapy(range 0-4) versus one(range 0-3) in pHGG. Five pHGG patients underwent re-irradiation. Median OS and PFS were 55 and 88 months in pLGG versus 13 and 7 months in pHGG (p < 0.001). Conclusion Outcomes for pBTG remain poor irrespective of histology, with significant shorter progression and survival in pHGG compared with pLGG. Management remains driven by histology. Prospective studies focusing on molecular profiling are needed to investigate the impact of upfront targeted therapy.

Magnetic resonance (MR) imaging is a noninvasive, nonionizing clinical modality widely used to detect and visualize anatomical and pathological conditions, including cancer. However, its effectiveness is often limited by low intrinsic sensitivity, insufficient targeting specificity, and poor contrast between normal and tumor tissues. Inspired by the natural use of multivalent interactions in biological adhesion, recognition, and signaling, we report a dual-multivalent enhancement strategy for designing a tetra-armed macrocyclic gadolinium(III)-based molecular MR contrast agent (GdCAG). This agent incorporates four carboxylic alkyl arms and four glucosyl targeting ligands, enabling simultaneous relaxivity enhancement and tumor-selective recognition. GdCAG exhibits significantly improved MR relaxivity as well as markedly enhanced tumor affinity, resulting in effective in vivo tumor-targeted MR imaging following intravenous administration. Compared with the monomultivalent analogue GdG (bearing only four glucosyl units) and the clinically approved control Gd-DOTA, GdCAG produces stronger whole-body MR signal enhancement and prolonged signal retention in healthy mice. In 4T1 breast cancer xenograft models, GdCAG further demonstrates a progressive MR signal increase at tumor sites, underscoring its superior tumor-targeting efficacy in vivo. Collectively, this work establishes a molecular dual-multivalent enhancement paradigm for advancing tumor-specific MR contrast design with broad potential for improving early cancer diagnosis, precision bioimaging, and image-guided therapies.