Precise tumor imaging is essential for accurate intraoperative decision-making, thereby directly influencing patient prognosis. Optical molecular probes enabling non-invasive, dynamic assessment of cancerous lesions are clinically crucial. However, current optical molecular probes face challenges in dodging false-positive and false-negative signals at once during imaging, limiting their clinical diagnostic use. Here, we introduce a class of lysosome-targeted, activatable optical probes (Dx-NH2), leveraging the increased lysosomal abundance during tumor metabolic reprogramming. Lysosomal protonation retains probes for better single-cell resolution and fewer false-negative signals. To enable more high-precision tumor imaging, we synthesized probe CN-D-GGT from CN-D-NH2 by introducing a γ-glutamyltransferase substrate, following our group's prior offensive and defensive integration strategy. Due to its smart design, CN-D-GGT, upon activation, shows marked changes in fluorescence and photoacoustic signals, enabling its application for multi-modal imaging. It also has high specificity, distinguishing cancer cells in co-culture (∼6-fold) and clearly differentiating tumors from normal and inflamed tissues (T/N or T/I signal ratios > 3.5). Importantly, it can also differentiate cancerous from adjacent tissues in clinical samples. This work has developed a probe that can accurately light tumors in complex pathological environments, with the potential to assist in intraoperative resection decision-making, avoid excessive or missed resection.
A new selective fluorescent probe based on a vitamin B6 derived hydrazone was synthesized and characterized for the detection of Al3+ and Ga3+ ions. The probe's selectivity and sensitivity were evaluated using UV-Vis, fluorescence, and NMR spectroscopy in a buffered DMSO/water solution, complemented by density functional theory (DFT) calculations to elucidate the electronic structure and coordination modes of the resulting complexes. The probe exhibited a notable "turn-on" fluorescence response upon binding Al3+ and Ga3+, with emission maxima at 466 nm and 477 nm, respectively, and detection limits as low as 48 nM for Al3+ and 33 nM for Ga3+. The probe showed high selectivity for these ions over a wide range of competing cations and anions, forming stable 1:1 complexes with log β' values of 5.98 for Al3+ and 6.28 for Ga3+. DFT calculations revealed a tridentate coordination mode via the phenolic oxygen, azomethine nitrogen, and carbonyl oxygen, with distinct electronic transitions for each complex, including a ligand-to-metal charge transfer character in the Ga3+ complex. The probe demonstrates reversibility and excellent solution stability, offering a simple and sensitive platform for the environmental and biological monitoring of aluminum(III) and gallium(III) ions.
Staphylococcus aureus is the leading cause of soft tissue infections that can be treated with antibiotics. However, it can also cause significant mortality and morbidity due to systemic infections and infections of surgical implants. Implant infections typically require invasive surgery, and treatment often necessitates removal of the implant because S. aureus biofilms are extremely difficult to eradicate with antibiotic treatment alone. Therefore, there is a significant need for improved diagnostic tools for rapid, non-invasive confirmation of S. aureus infections. We recently developed an activity-based probe containing an oxadiazolone electrophile that selectively labels the S. aureus -specific serine hydrolase, FphE, by covalent binding to its active site serine residue. Here we describe a Cy5-labeled version of the probe, JJ-OX-012, and its characterization as an imaging agent for detecting biofilms both in vitro and in vivo . The probe labeled S. aureus biofilms in vitro , with virtually no background labeling of bacteria that lack FphE expression. Furthermore, we demonstrate that JJ-OX-012 can be used for non-invasive fluorescent imaging as a way to detect S. aureus biofilms in vivo . Overall, these findings support the potential for using covalent probes targeting FphE as imaging agents for rapid detection and diagnosis of staphylococcal infections in vivo .
Miniprobe endoscopic ultrasonography (mEUS) combines high-resolution imaging of the gastrointestinal (GI) wall and bile ducts with ease of applicability during routine endoscopy. This narrative review aims to provide an overview of known and emerging fields of application for mEUS in gastrointestinal endoscopy. After its initial development in pancreatobiliary scenarios in the early 1990s, mEUS has been recently reconsidered a third-space endoscopic technique that is progressively developing and spreading for the treatment of early gastrointestinal neoplastic lesions. The high spatial resolution of mEUS provides an accurate assessment of the degree of submucosal invasion in early esophageal, gastric, and colorectal neoplasia, while the small caliber of catheters allows for mEUS employment in settings where standard echoendoscopes are impractical (e.g., severe stenoses or proximal colonic lesions). Beyond cancer staging, mEUS offers point-of-care characterization of subepithelial lesions by defining the layer of origin and echo-pattern, eventually defining endoscopic resectability, but definitive diagnosis remains histological. In pancreatobiliary diseases, miniprobe intraductal ultrasonography (IDUS) shows its strongest application for indeterminate biliary strictures when endoscopic retrograde cholangiopancreatography (ERCP)-based sampling strategies and brushing cytology show inconclusive diagnoses, and in choledocholithiasis, particularly for the detection of small stones/sludge and confirmation of duct clearance. IDUS is also valuable for the staging of ampullary tumors, for longitudinal extension mapping in hilar cholangiocarcinoma and for selected portal biliopathy scenarios. Overall, mEUS and IDUS are high-resolution adjuncts that can meaningfully refine local decision-making in the treatment of superficial epithelial/subepithelial tumors or lesions involving the bile ducts. Limitations include shallow penetration, lack of tissue acquisition capability, a relative increase in post-ERCP pancreatitis risk for intraductal use, and substantial cost with limited availability in lower-volume centers.
The widespread residual ciprofloxacin (CIP) poses severe environmental and health risks, demanding efficient detection methods. Herein, a Zr-Tb bimetallic MOF (ZTM) was green-synthesized via a room-temperature aqueous route with disodium terephthalate as ligand, and developed as a ratiometric fluorescent probe for CIP detection. Structural characterization confirmed Tb3+ was successfully incorporated into the Zr-MOF framework, endowing ZTM with high stability and excellent luminescence. The absorption edge of ZTM (320-330 nm) overlapped with CIP's 330 nm absorption peak, so 327 nm was selected as the excitation wavelength. Under this excitation, ZTM showed a strong Tb3+ emission at 657 nm; upon CIP addition, the 657 nm peak was quenched, while the 491 nm emission was enhanced, realizing a distinct ratiometric response. The ratio I491/I657 was linear with CIP concentration (0.5-25 μM, R2 = 0.992), with a limit of detection far below the statutory 30 μM limit (0.16 μM). ZTM also exhibited excellent selectivity, good pH tolerance (5.0-8.0) and rapid response (1 min). Mechanism analysis revealed that the response was mainly due to the inner filter effect (IFE) between ZTM and CIP. This work provides a green-synthesized MOF probe for sensitive and selective CIP detection in environmental samples.
Alterations in the ratio of oxidized and reduced nicotinamide adenine dinucleotide (NAD+/NADH) reflect the intracellular redox state and have been implicated in a broad spectrum of pathological conditions, including neurogenetic disorders, heart failure, and liver diseases. In the present study, we demonstrate the selective detection of probe-derived NAD+ and NADH signals in mouse liver extracts by means of a triple-resonance nuclear magnetic resonance (NMR) spectroscopy technique. We prepared 13C/15N-enriched nicotinamide riboside (13C/15N-NR), which undergoes enzymatic conversion to NAD+ and NADH in the liver, and detected these labeled metabolites by 1H-{13C-15N} triple-resonance NMR measurements. This study provides a methodological proof-of-concept for the selective detection of NAD-related signals derived from a stable-isotope labeled probe in mouse liver extracts.
The pathological mechanisms underlying neurodegenerative diseases remain poorly defined, largely due to the lack of tools capable of detecting molecular alterations before the onset of clinical symptoms. Here we successfully achieve targeted profiling of dopamine (DA) and nontargeted profiling of amino acid (AA) molecules in the lesioned substantia nigra of Parkinson's disease (PD) mouse by intergrating ex vivo surface-enhanced Raman spectroscopy (SERS) probes with concurrent in vivo electrophysiological recordings in the primary motor cortex. The PD model was established by stereotaxic unilateral injection of 6-hydroxydopamine (6-OHDA) into the right striatum of mice, while the left sham side was used as the reference. At early stage of PD model, a sandwich-structured SERS tag enables highly specific targeted profiling of picomolar-level DA, and a feedforward neural network resolves highly overlapping AA spectra, allowing reliable identification of AA components at physiological micromolar concentrations. In the lesioned substantia nigra, results reveal a rapid decline in DA levels within 6 h after 6-OHDA injection, followed by a marked elevation of glutamate (Glu) at 9 h; while the primary motor cortex at 9 h starts to emerge pathological β-band hypersynchronization and abnormal β-γ phase amplitude coupling. These molecular and circuit-level disturbances clearly precede overt motor asymmetry that becomes evident only at 27 h postlesion. Integrated transcriptomic and qPCR analysis identifies Glu as a central molecular hub linking early neurochemical imbalance to subsequent neural circuit dysfunction. The findings indicate a DA-depletion-triggered and Glu-centered excitotoxic cascade, and also prospect a early therapeutic window during which restoring Glu homeostasis, enhancing metabolic resilience, or mitigating oxidative stress may help prevent subsequent network destabilization. This synergistic SERS-electrophysiology suite enables time-resolved chemical-to-neurophysiological mapping and provides a general framework for investigating molecular-to-circuit transitions in neurodegenerative disorders.
Inflammatory skin diseases, such as atopic dermatitis, hidradenitis suppurativa and psoriasis, involve chronic aberrations to innate and adaptive immunity, driven by pro-inflammatory cytokines. Various minimally invasive methods exist that allow for proteomic analysis of affected skin lesions in microscale concentrations. However, analyzing cytokines in small skin samples using traditional immunoassays is challenging due to many cytokines being detectable only at pico-scale concentrations. Here, a digital surface-enhanced Raman spectroscopy (SERS) immunoassay has been developed for multiplex detection of IL-17A, IL-22, IL-23 and TNF in punch biopsy skin using psoriasis as a model. It is performed using single-molecule counting via analyte compartmentalization on a nanopillar array and single-particle active SERS nanotags. This SERS nanopillar assay demonstrated a high degree of specificity and sensitivity, detecting cytokines down to 104 aM. Promisingly, this assay successfully detected cytokines in microscopically derived skin punch biopsy samples containing 13.84 µg to as little as 0.34 µg of total protein, revealing distinct cytokine profiles. The assay was also able to show the differences in cytokine levels between perilesional and lesional psoriasis skin samples. The high detection sensitivity of the digital SERS nanopillar assay, combined with cytokine profiling in biopsy samples, shows promise for sensitive immunological diagnosis and therapeutic monitoring of inflammatory skin diseases.
Collagen, the most abundant protein in animals, is a key structural component of muscle and connective tissues. Its structural integrity is strongly influenced by interactions with water; however, the molecular mechanisms underlying these effects remain poorly understood. Here, we investigate dehydration-induced perturbations in collagen dynamics within the native bone extracellular matrix (ECM) using 13C solid-state Nuclear Magnetic Resonance (NMR) relaxation measurements (T1 and T2) and associated rotational correlation times. This residue-specific approach reveals distinct dynamic behavior of the aliphatic carbons of the Gly-Pro-Hyp triplet and alanine, collectively constituting ∼70% of type I collagen. The 13C correlation times (10-6-10-8 s) demonstrate pronounced motional heterogeneity: dehydration predominantly restricts hydroxyproline Cβ, whereas H/D-exchanged perturbs hydroxyproline Cα, Cβ, and Cγ, as well as glycine Cα. These findings establish 13C relaxation as a powerful tool for probing water-mediated collagen dynamics in native systems.
There is a lack of approaches to detect and kill metastatic cells. As an agent for metastasis targeting, a cyclic peptide BLMP6 has been previously characterized. As a step toward translation, we designed AZDye555-labeled BLMP6 and demonstrated its homing to metastases of human MDA-MB-231 cells in mice. We show that 68Ga-radiolabeled BLMP6 can be used for the detection of MDA-MB-231 metastases. We designed a peptide-drug conjugate consisting of monomethyl auristatin E (MMAE) and BLMP6. We show that MMAE-BLMP6 kills MDA-MB-231 cells in cell culture and in vivo. In mouse models of lung metastases, treatment with MMAE-BLMP6 suppressed metastasis growth and improved survival. Based on BLMP6 similarity to latent transforming growth factor β binding protein 4 (LTBP4), we identified fibulin-4 as a BLMP6 target. We show that BLMP6 mimics the LTBP4 domain binding to fibulin-4 and selectively binds to fibulin-4 in vitro. Fibulin-4 knockout in cancer cells abrogated BLMP6 homing to lung metastases in mice. Fibulin-4 expression was found to be increased in invasive and metastatic human breast cancer and correlated with the binding of AZDye555-BLMP6 in human tissue sections. Our results suggest that fibulin-4 and BLMP6 may be further developed for the detection and targeting of metastatic human cancers.
Easier measurement of 17β-estradiol could promote the early diagnosis and treatment of medical conditions in women. In this study, we developed a fluorescence-based assay using a nucleic acid aptamer labeled with a fluorescent dye for the detection of estrogen. Upon binding to 17β-estradiol, the aptamer undergoes a conformational change, resulting in a measurable change in fluorescence intensity. The assay enables rapid detection within 30 min, with a limit of detection of 0.2 pg/mL and a linear dynamic range of 1-1000 pg/mL. High selectivity toward 17β-estradiol was confirmed against structurally related compounds. The method was successfully applied to human saliva samples, demonstrating high sensitivity, precision, and reproducibility with recoveries of 98.8% and coefficients of variation below 3.0%. In addition, a compact desktop fluorescence detector was developed, allowing direct measurement in polymerase chain reaction tubes without sample transfer, thereby simplifying the procedure and minimizing sample loss. These results demonstrate that the proposed system provides a simple and practical platform for estrogen detection in biological samples and has potential applications in clinical and research settings.
Artificial light at night (ALAN) is an increasingly significant environmental disturbance, as it disrupts natural light-dark cycles that regulate daily and seasonal physiological processes and phenological events of all organisms. The use of artificial lighting in urban areas is rapidly increasing each year due to the rising number of unregulated vehicles, as well as the widespread installation of decorative lights, digital advertising boards, and streetlights. The objective of this research was to determine the impacts of artificial light at night (ALAN) on various ornamental garden plants such as Dieffenbachia seguine, Lawsonia inermis, Alocasia cucullata, Cynodon dactylon and Dypsis lutescens through the analyses of chlorophyll fluorescence transients, specific and phenomenological energy fluxes, density of functional PSII RCs, quantum yields (Fv/Fm, ϕE0), non-photochemical quenching (Kn) and photochemical quenching (Kp), superoxide dismutase (SOD) activity, and concentrations of chlorophylls, malondialdehyde (MDA) and starch content. The results of the present study highlight that plant responses to ALAN vary among species. The present investigation demonstrates that D. lutescens and C. dactylon exhibit pronounced sensitivity to ALAN, whereas D. seguine, L. inermis, and A. cucullata display a comparatively higher degree of tolerance. These findings underscore the need to preferentially select ALAN-tolerant species for urban plantation programs to minimize the ecological consequences associated with light pollution. Moreover, the study identifies specific photosynthetic parameters (OJIP transients, ET/CS, RC/CS, Kp, Kn, and PICS) along with key biochemical indicators (SOD activity, MDA accumulation, and chlorophyll content) as reliable diagnostic markers for distinguishing ALAN-sensitive and ALAN-tolerant species, thereby supporting informed species selection for sustainable urban greening.
Diacylglycerols (DAGs) are central intermediates in lipid metabolism and signaling, yet their trafficking and persistence within lipid droplets (LDs) remain incompletely understood due to the lack of chemically stable, DAG-mimetic imaging tools. Here, we report the development of a family of solvatochromic fluorescent lipid analogs, termed DONDI, designed to probe DAG-associated dynamics at LDs. These probes are based on a 1,8-naphthalimide scaffold conjugated to modified aminoglycerol backbones bearing oleoyl chains to mimic native glycerolipids. Biophysical characterization and atomistic molecular dynamics simulations revealed probe-specific membrane insertion and hydrogen-bonding behaviors consistent with distinct lipid-mimetic properties. Live-cell imaging in NIH 3T3 fibroblasts demonstrated that DONDI probes were efficiently internalized and selectively accumulated within lipid droplets. Structure-function analysis identified DONDI-5 as the closest mimic of 1,2-diacylglycerol, displaying rapid uptake, strong LD enrichment, and prolonged intracellular retention without detectable relocalization to other cellular membranes. These properties enabled sustained visualization of LD-associated DAG pools over extended time scales. Collectively, this work establishes DONDI-5 as a chemically stable DAG-mimetic probe and provides direct experimental support that DAGs can be transported to and transiently stored within lipid droplets without prior conversion to triacylglycerols.
In this paper, SiQDs were synthesized using 3-aminopropyltrimethoxysilane, an organosilicon source, via the room temperature stirring method under atmospheric pressure. Based on the "Turn-off" and "Turn-on" fluorescence response mechanisms, the SiQDs/Fe3+ fluorescent probe was constructed to quantitatively detect glyphosate according to the interaction between Fe3+ and glyphosate. Subsequently, the impacts of pH, incubation temperature, and reaction time on the detection of glyphosate were systematically investigated. Under the optimized detection parameters, the fluorescent probe exhibited a linear range of 2-10 μg/mL and a detection limit of 394.74 ng/mL. The constructed fluorescent probe demonstrated outstanding anti-interference performance. It was applied to actual samples of potato and yam, yielding satisfactory detection results with recovery values between 91.69% and 104.53%. These findings provide novel ideas and theoretical support for glyphosate residue detection.
Early and accurate detection of Pseudomonas aeruginosa (P. aeruginosa) is critically important in perioperative care to prevent severe healthcare-associated infections and guide timely antimicrobial intervention. Herein, we report a novel biosensing strategy for sensitive and label-free detection of P. aeruginosa by integrating F23 aptamer-mediated target recognition, garland rolling circle amplification (RCA)-triggered self-priming extension, and SYBR Green I (SG-I)-based fluorescence readout. The capture probe, comprising the F23 aptamer and a primer strand immobilized on magnetic nanoparticles, specifically recognizes P. aeruginosa and releases the primer to initiate dumbbell probe circularization and subsequent RCA. The resulting RCA products are cleaved by a nicking endonuclease to generate fragmented DNA, which then hybridizes with a hairpin probe to prime cyclic self-extension reactions, producing abundant double-stranded DNA for SG-I intercalation and fluorescence enhancement. Under optimized conditions, the proposed method achieves a detection limit as low as 2.3 CFU/mL with a wide linear range from 10 to 106 CFU/mL. The assay exhibits excellent specificity against non-target bacteria, robust stability during storage, and satisfactory anti-interference capability in complex clinical matrices. Validation using clinical samples demonstrates excellent agreement with the gold-standard colony counting method while reducing the assay time to less than 2.5 h without requiring nucleic acid extraction or thermal cycling. With its label-free design, isothermal amplification, and operational simplicity, this strategy holds great promise for point-of-care testing in perioperative settings and can be readily adapted for detecting other pathogens by substituting the corresponding aptamer.
Rotational speed monitoring is essential in many industrial and electromechanical systems. This paper presents a rotational speed measurement method based on a wireless impedance sensing system leveraging the radio-frequency coupling between a passive resonant tag and a coplanar waveguide (CPW) probe. The sensing mechanism exploits periodic variations in the real part of the probe impedance caused by the relative alignment between the rotating tag and the stationary probe. While the impedance signal is inherently periodic, the usable speed range of sampling-based measurement systems is fundamentally constrained by their acquisition rate. To overcome this limitation without requiring higher-rate instrumentation, an equivalent-time sampling (ETS) reconstruction approach is proposed. Sparse and nonuniform impedance samples collected over multiple revolutions are mapped into an equivalent phase domain and combined to reconstruct the waveform associated with a single rotation period. The method is reader-agnostic in principle, as it only requires time-stamped monitoring of a periodic RF observable at a selected frequency; however, experimental validation in this work is performed using a vector network analyzer (VNA). Experimental results obtained on a rotating platform with speeds ranging from 150 RPM to 4000 RPM demonstrate that the proposed method reduces the mean relative estimation error to below 5% across the full range, compared to errors exceeding 70% for conventional peak-based estimation above 1000 RPM. These results highlight the effectiveness of the ETS approach in extending the operational range of RF impedance-based rotational sensing under severe undersampling conditions. The proposed framework is generalizable to other periodic RF sensing configurations where signal periodicity can be exploited across multiple acquisition cycles.
To investigate the mechanistic role of Sijunzi decoction (SJZD) in overcoming chemoresistance through the suppression of adaptive metabolic responses in non-small cell lung cancer (NSCLC). Chemical profiling of SJZD-derived components in systemic circulation was conducted using liquid chromatography-tandem mass spectrometry (LC‒MS/MS) in Sprague-Dawley rats. Multiomics integration and network pharmacology were employed to identify convergent targets shared by the bioactive constituents of SJZD and genes associated with cisplatin resistance. In vitro functional assessments using cisplatin-resistant human lung adenocarcinoma (A549/DDP) cells included the following: quantification of cell viability via Cell Counting Kit-8 (CCK-8) assays; evaluation of mitochondrial bioenergetics through targeted metabolomic profiling; and ultrastructural characterization of ferroptotic morphology via transmission electron microscopy (TEM). Cellular redox homeostasis was dynamically monitored using fluorescent probes, including a DCFH-DA probe for reactive oxygen species (ROS) and a C11-BODIPY581/591 probe for lipid peroxidation. siRNA-mediated gene silencing and immunohistochemical analysis were performed to elucidate the functional hierarchy of the p62/Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant axis. Complementary in vivo validation was performed using BALB/c nude mice bearing A549/DDP xenografts, with longitudinal monitoring of tumor progression under SJZD treatment regimens. Untargeted metabolomics of SJZD-medicated serum revealed 392 differentially abundant metabolites, with pathway enrichment revealing significant dysregulation of glutamine metabolism. Structural validation confirmed 55 bioactive components of SJZD in serum, including glycyrrhizin, ginsenoside Ro, liquiritigenin, and atractylenolide I. Integration of these components with disease targets yielded 355 overlapping genes associated with both SJZD activity and cisplatin-resistant NSCLC, with significant enrichment in oxidative stress response pathways. Experimental assays confirmed that SJZD induced ferroptosis in cisplatin-resistant A549/DDP cells, as evidenced by disrupted iron homeostasis, lipid peroxidation, and characteristic mitochondrial damage. These effects and subsequent cell death were specifically abrogated by the ferroptosis inhibitor ferrostatin-1 (Fer-1) but not by apoptosis inhibition, confirming that ferroptosis is the primary mechanism of cell death. Mechanistically, the inhibition of p62/Keap1/Nrf2 signaling was involved in the modulation of SJZD-induced ferroptosis both in vitro and in vivo. SJZD counteracts metabolic adaptation through ferroptosis mediated by the inhibition of p62/Keap1/Nrf2 in cisplatin-resistant NSCLC.
Disease-specific alpha-synuclein (αsyn) strains have been linked to different synucleinopathies. Current αsyn biomarkers are limited to binary detection of pathogenic αsyn in peripheral tissue biopsies or fluids, limiting differential diagnosis. Hence, there is an urgent need for methods that allow strain-specific detection and characterization of αsyn strain architecture. Notably, luminescent conjugated oligothiophenes (LCOs) have been successfully used to detect distinct protein strain conformers in prion diseases and Alzheimer's disease, highlighting their utility in differentiating disease-specific amyloid structures. Species-dependent differences in αsyn structure are increasingly recognized as one of the critical aspects that shape how fibrils form, propagate and interact with molecular LCO probes. Here, we evaluate the potential of the LCO h-FTAA to differentiate species-specific αsyn strains and conduct a translational investigation using peripheral cardiac tissue of a gut-first synucleinopathy rodent model. Our in vitro data demonstrate strain-specific probe-fibril interactions, reflecting a differential strain architecture and cellular micro-environment. While h-FTAA binds with comparable efficiency to mouse (mo-) and human (hu-) pre-formed fibrils (PFFs), h-FTAA exhibits markedly lower quantum yield when bound to moPFFs versus huPFFs. Spectral imaging revealed h-FTAA-moPFF binding produces blue-shifted maxima (505-550 nm), contrasting with the red-shifted maxima (545-580 nm) of huPFFs. Fluorescence lifetime imaging microscopy confirmed h-FTAA's intrinsic sensitivity to species-dependent variations through distinct temporal fluorescence signatures (moPFFs: ~0.60-1.5 ns vs. huPFFs: ~0.65-1.0 ns). Our translational investigation showed h-FTAA binding to peripheral cardiac pathology exhibits comparable red-shifted emission, but distinct fluorescence lifetimes of h-FTAA-bound aggregates in moPFF-injected (~1.0-1.4 ns) versus huPFF-injected (~0.69-0.8 ns) rats. Interestingly, we observed distinct blue-shifted emission profiles in a few selected regions of the heart of moPFF-injected rodents, further characterized by extra-long fluorescence decay shifts (~1.5-1.9 ns), reflecting differences in both aggregate conformation and maturity in moPFF-induced compared with huPFF-induced rats. Taken together, our findings underscore the potential of LCO ligands, like h-FTAA, to enable more precise disease staging and diagnosis through peripheral biopsies, complementing existing αsyn biomarker methods.
Plasmodium falciparum parasites with deletions of the histidine-rich protein 2 and 3 ( hrp2 and hrp3 ) genes evade detection by common rapid diagnostic tests (RDTs) and pose a growing threat to malaria control. While these deletions have emerged in multiple regions globally, the evolutionary forces driving their spread remain unclear. Here, we analyze 1,215 P. falciparum samples collected between 2003 and 2018 in Loreto, Peru. This region experienced a major decline in malaria transmission following the Project for Malaria Control in Andean Border Areas (PAMAFRO) and now harbors a high proportion of hrp2/3 deleted parasites despite limited RDT use. Using molecular inversion probe (MIP) sequencing across > 2,000 genome-wide loci, we observed a marked reduction in genetic diversity, increased clonality, and fixation of parasites with deletions of both hrp2 and hrp3 genes ( hrp2-/3- ) over time. Identity-by-descent (IBD) analysis revealed rapid expansion of a single hrp2-/3- dominant lineage in the post-PAMAFRO period, consistent with clonal replacement after intense malaria control. Targeted sequencing of the hrp2/3 regions showed conserved deletion breakpoints across three different lineages, indicative of recombination of a common haplotype into distinct genetic backgrounds. To investigate the evolutionary forces driving the fixation of hrp2-/3- in Loreto, we simulated allele frequency trajectories under different selection coefficients. We found that fixation of hrp2-/3- due solely to genetic drift (selection coefficient s = 0) is unlikely; a selection coefficient of s ≥ 0.03 was required for fixation to occur consistently. However, our simulations also indicate that a genetic bottleneck caused by PAMAFRO increased the likelihood of fixation through drift by 4.5- to 17-fold depending on the population. These findings suggest that hrp2-/3- fixation was likely driven by a combination of demographic changes resulting from PAMAFRO and selective advantage unrelated to RDT use. Our results demonstrate how intensive malaria control efforts can reshape parasite populations and underscore the value of expanded genomic surveillance as countries move toward malaria elimination.
This study reports the synthesis and characterization of a novel benzimidazole-derived Schiff base (BIMPB) via the condensation of (1H-benzo[d]imidazol-2-yl)methanamine with 1-phenylbutane-1,3-dione. The structure was confirmed using 1H-NMR, 13C-NMR and FT-IR spectroscopy. Photophysical properties were extensively evaluated, revealing a strong S0 → S2 transition at 212 nm and fluorescence emission peaks at 396 and 410 nm, corresponding to π → π* and n → π* transitions. BIMPB demonstrated significant sensitivity to pH variations, exhibiting blue shifts of 11-23 nm across different environments. Furthermore, the compound acts as a fluorescent chemosensor for Cu2+ and Ca2+ ions, where coordination leads to a substantial reduction in fluorescence intensity accompanied by a distinct blue shift. The interaction between BIMPB and DNA was investigated using UV-Vis and fluorescence titration. The results showed a hypochromic effect and a minor shift in the absorption peak from 342 nm to 340 nm, suggesting a binding mechanism dominated by intercalation or electrostatic interactions. A high binding constant (Kb = 2.1 × 105 M-1) and a fluorescence quenching efficiency of 58.9% confirm the formation of a stable complex. Stern-Volmer analysis indicated a static quenching mechanism. These experimental findings, supported by molecular docking studies (binding energy = -8.3 kcal/mol), highlight the potential of BIMPB as a sensitive molecular probe for DNA-targeting and chemical sensing applications.