In the rapidly evolving field of single-molecule sensing, solid-state nanopores have emerged as transformative tools for the label-free detection of biomolecules, ranging from DNA polymers to proteins. Yet, with two dominant platforms─glass nanopores and silicon nitride (SiNx) nanopores─researchers face a pivotal choice: which architecture best unlocks superior performance? Here, we deliver a head-to-head experimental comparison under comparable experimental conditions, benchmarking noise characteristics, signal-to-noise ratios (SNRs), and translocation dynamics for DNA and protein analytes across matched nanopore sizes. Our findings reveal compelling trade-offs: glass nanopores excel in DNA sensing, achieving record SNR values of >80 in 5 nm nanopores (4 M LiCl, 50 kHz filter cutoff) due to their conical geometry that focuses electric fields. In contrast, SiNx nanopores dominate protein detection with SNR values of >120, leveraging thin membranes for enhanced current blockade from volume exclusion. Comprehensive performance metrics─including unfolded DNA fraction, backward-to-forward translocation time ratio, translocation frequency, and perturbed events─also show distinct translocation behaviors of biomolecules in the two nanopore platforms. These insights, supported by finite-element simulations, establish a mechanistic framework for nanopore selection, favoring conical glass nanopores for polymeric analytes and SiNx membrane nanopores for compact biomolecules. This work not only sets benchmarks for nanopore sensitivity but also enables the development of tailored sensors in diagnostics, sequencing, and beyond, advancing nanotechnology for high-resolution biomolecular analyses.
Localized chemotherapy offers a promising strategy to improve therapeutic efficacy while minimizing the systemic toxicity of conventional cancer treatment, particularly following tumor resection. Electrospun nanofibers are well suited for this purpose due to their high porosity, extracellular matrix-mimicking architecture, and capacity for localized drug release. In this study, electrospun nanofibers based on PCL and PLGA were developed for localized cancer therapy. Three distinct nanofibrous architectures were fabricated: PCL nanofibers, PCL-PLGA blended nanofibers, and PCL-PLGA multilayered (tetra-layered) nanofibers, and their encapsulation efficiency was determined by high-performance liquid chromatography (HPLC). Scanning electron microscopy confirmed uniform, bead-free nanofibrous morphologies, while Fourier transform infrared spectroscopy and thermal analyses verified effective polymer blending, molecular interaction, drug incorporation, and enhanced thermal stability. The incorporation of PLGA altered the degradation rate and surface wettability of the nanofibers, enabling modulation of drug release behavior. Biological evaluations demonstrated acceptable hemocompatibility, favorable interactions with RAW 264.7 macrophages, and high cytocompatibility across all formulations. Importantly, nanofiber architecture significantly influenced release profiles (curcumin dye as a model), with multilayered or blend nanofibers exhibiting reduced burst release and prolonged drug delivery compared to single-polymer systems. In addition, proliferation clonogenicity and western blotting assays confirm their corresponding high cytotoxic responses (docetaxel as a model). Overall, this work demonstrates that architectural and compositional engineering of PCL-PLGA electrospun nanofibers provides a robust and adaptable platform for localized, sustained cancer therapy.
Nanotechnology-enabled NPK fertilization combined with biostimulants offers a sustainable approach to enhance crop productivity, resource-use efficiency, and environmental performance in specialty crops. A two-year (2022-2023) factorial experiment (3 × 2), arranged in a completely randomized design, evaluated the interactive effects of nano humic acid-silicic acid-based Triple 20 NPK fertilizers (nano-NPK) applied at 40, 80, and 120 kg ha ⁻ ¹, with and without 0.3% salicylic acid (SA) as biostimulant, on processing tomato (Solanum lycopersicum L. cv. BHN 685) grown in a low-fertility soil under drip-irrigated, raised bed plasticulture. Conventional Triple 20 NPK fertilization at 120 kg ha ⁻ ¹ served as the control. Multivariate statistical analyses demonstrated that nano-NPK fertilization and SA, alone or in combination, significantly improved tomato yield components, water use efficiency (WUE), and fertilizer use efficiency (FUE), while reducing cull fruit and increasing marketable yield. Among treatments, 80 kg ha ⁻ ¹ nano-NPK combined with 0.3% SA produced both total and marketable yields equivalent to or exceeding those obtained with 120 kg ha ⁻ ¹ nano-NPK or conventional fertilization, alongside higher nutrient, and water utilization. These improvements were associated with enhanced nutrient bioavailability, uptake, and photosynthetic performance due to nano-enabled NPK fertilization, with SA further promoting plant growth and fruit quality. This combination reduced fertilizer input by up to 33% without compromising yield, achieving WUE and FUE comparable to or better than conventional NPK fertilization (120 kg ha-1). Economically, 80 kg ha ⁻ ¹ nano-NPK + 0.3% SA achieved the highest benefit-cost ratio (1.26) and net return (US $1,988 ha ⁻ ¹), outperforming conventional NPK fertilization. Environmental assessment indicated improved energy use efficiency (4-6%) and lower greenhouse gas (GHG) intensity per unit of marketable yield. Although total GHG emissions were statistically similar at higher application rates, nano-NPK, SA, or their combination reduced GHG intensity, highlighting their sustainability advantage. Overall, integrating 80 kg ha ⁻ ¹ nano-NPK with 0.3% SA optimizes yield, profitability, and environmental stewardship, offering an efficient pathway for sustainable intensification of tomato production.
Epitaxial growth of one-dimensional semiconductors provides a compelling route to vertically integrated heterostructure architectures with coherent interfaces and a high crystalline quality. However, vapor-phase approaches are typically constrained by the thermal budget and require complex infrastructure, whereas solution-liquid-solid (SLS) syntheses generally yield colloidal products with compromised crystallinity and limited capability for monolithic integration. Here, we report a laser-induced solution-liquid-solid (laser-SLS) synthesis method that enables epitaxial growth of vertically aligned, single-crystalline germanium (Ge) nanowires, a group-IV semiconductor for advanced electronic applications. Through the use of bismuth (Bi) catalysts in the laser-SLS process, periodically ordered Ge nanowire arrays are obtained with uniform morphology and a well-defined epitaxial relationship with the substrate. Pulsed-laser irradiation provides spatially confined photothermal heating at the catalyst-substrate interface. This localized heating promotes the precursor reaction and sustains rapid nanowire growth, while the surrounding solution remains at a globally low temperature. Electrical measurements show nearly linear current-voltage characteristics with low contact resistance, consistent with a high carrier concentration in the nanowires and an epitaxial nanowire-substrate junction. By enabling epitaxial nanowire growth under low thermal budgets, laser-SLS may provide a viable pathway to mitigate persistent contact challenges in n-type Ge and support opportunities for heterogeneous and monolithic integration in advanced CMOS and nanoelectronic technologies.
The escalating global challenge of Antimicrobial Resistance (AMR) underscores the urgent need for alternative therapeutic approaches beyond conventional antibiotics. Nanoparticles (NP), with their distinct physicochemical properties, tunable morphologies, high surface reactivity, and structural diversity, have emerged as promising candidates in combating microbial infections. This review adopts a dimensional framework encompassing zero-dimensional (0D), one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) nanostructures to systematically classify and analyze their antimicrobial mechanisms. Key bactericidal pathways explored include the generation of Reactive Oxygen Species (ROS), physical disruption of microbial membranes, controlled metal ion release, and light-mediated effects such as photothermal and photodynamic actions. Each dimensional class of NPs exhibits unique interactions with bacterial cells, influenced by parameters such as geometry, crystallinity, surface chemistry, and specific surface area, all of which collectively dictate their antimicrobial potency and selectivity. Furthermore, nanotoxicity, scalability, and clinical applications have also been addressed. This review focuses on the rational design and optimization of next-generation nanomaterials by linking nanostructural characteristics to specific antibacterial pathways. Such an approach provides an outline for customizing NP-based systems to more effectively fight resistant infections. Furthermore, we discussed the development of novel, multi-mechanistic techniques for reducing the global burden of AMR and promoting the transition of nanotechnology-enabled antimicrobials from laboratory research to real-world clinical and environmental applications.
In this study, beta glucan nanoparticles were fabricated and encapsulated with Doxorubicin for an effective drug delivery for triple negative breast cancer treatment. The synthesized nanoparticles were characterized by FTIR, TEM, SEM, DLS and zeta potential analysis. A drug encapsulation rate of 80% was achieved and drug release studies displayed a better release of drug from encapsulated glucan nanoparticles in acidic media. In vitro cytotoxicity and cellular uptake were evaluated by MTT and fluorescence microscopy, respectively where the IC50 concentrations for Dox and Dox loaded nano glucans were found to be 2.5 and 1µg/ml respectively. SEM, TEM and DLS results showed that beta glucan nanoparticles have a size distribution between 30-100 nm. FTIR and zeta potential analysis confirmed the loading of Dox. The results over MDA-MB-231 cells showed that Dox loaded beta glucan nanoparticles were effectively internalized and had more cytotoxic activity with respect to free drug.
This study examines magnetohydrodynamic (MHD) heat and mass transfer of a ternary hybrid nanofluid over a rotating sphere incorporating thermophoretic particle deposition, thermal radiation, activation energy and chemical reaction effects. The nanofluid consists of [Formula: see text]-[Formula: see text]-[Formula: see text] nanoparticles dispersed in propylene glycol. The governing boundary layer equations are transformed into a system of nonlinear ordinary differential equations via similarity transformations, which are solved using the Gegenbauer wavelet method. Results indicate that increasing magnetic interaction suppresses velocity due to Lorentz force effects while enhancing thermal distribution. Higher nanoparticle volume fraction improves heat transfer but increases viscous resistance. Thermophoresis and activation energy significantly influence mass transfer characteristics. Comparative analysis reveals that the ternary hybrid nanofluid exhibits enhanced thermal performance relative to the corresponding hybrid nanofluid configuration. The findings provide theoretical insight into MHD-controlled rotating nanofluid systems.
Autoimmune diseases pose a significant challenge to modern medicine due to their complicated and poorly understood mechanisms, which hinder effective diagnosis and treatment. The rising global incidence of autoimmune disorders is projected to place increasing strain on healthcare systems and financial resources. In response, nanotechnology has emerged as a promising avenue for both the diagnosis and treatment of these conditions. Among various nano-technological approaches, nanoparticles have garnered particular attention due to their advantageous properties including biocompatibility, enhanced drug bioavailability and efficient permeability across biological membranes. Furthermore, their unique characteristics such as magnetic responsiveness, anti-inflammatory, and antimicrobial capabilities, enable precise drug delivery and improved therapeutic outcomes, as well as the potential for earlier disease detection. Despite these promising developments, the clinical translation of nanoparticle-based strategies faces challenges including concerns regarding their stability in vivo and the need for further research to validate their safety and efficacy. While current diagnostic tools remain limited, certain nanoparticles have already received approval from the US Food and Drug Administration, demonstrating their potential for clinical application. This review aims to highlight the recent advances in use of nanoparticles for the diagnosis and treatment of autoimmune diseases, and to explore their prospective role in future clinical practice.
Osteosarcoma is featured with an immunosuppressive tumor microenvironment (TME) and limited therapeutic efficacy. Herein, we report a pH-responsive nanoplatform based on calcium phosphate (CaP)-coated Prussian blue nanoparticles (PB@CaP NPs) for optimized systemic delivery and antitumor immune response. The CaP interface inhibits the protein corona formation in blood, reducing complement-mediated clearance and prolonging circulation, and enhancing tumor accumulation of the nanoparticles. The pH-responsive dissolution of PB@CaP NPs enables the sequential release of calcium ions in the acidic TME and iron ions in lysosomes, together with the peroxidase-like catalytic activity of the PB core, establishing a synergistic ion/nanozyme signaling axis that triggers robust ROS generation and oxidative stress, thereby reprogramming tumor-associated macrophages from an immunosuppressive M2-like to a pro-inflammatory M1-like phenotype and remodeling the tumor immune microenvironment. This study provides a rational surface engineering strategy for nanoimmunotherapy.
Noble metal dichalcogenides (NTMDs), such as PtTe2, provide a platform in which noble metal centers are embedded within chalcogen-coordinated lattices, enabling modulation of the electronic structure of Pt while potentially maximizing noble metal utilization in ultrathin architectures. However, the strong interlayer coupling commonly observed in NTMDs makes the preparation of atomically thin structures challenging, limiting access to their coordination-dependent catalytic properties. In this work, a solvothermal strategy is given for the heteroepitaxial vertical growth of ultrathin PtTe2 nanosheets (NSs) on Te-substituted Cu1.81S nanorods. Surface anion exchange of Cu1.81S nanorods generates metastable Cu6-yTe4 and Cu7Te4 phases with abundant stacking faults, where the Cu6-yTe4 domains act as preferential nucleation sites for PtTe2 epitaxy, leading to vertically aligned NSs with a few-unit-cell thickness. Encouraged by this result, we further attempted the growth of ultrathin PtTe2 NSs on the peripheral facets of Cu1.81S nanoplates to fully exploit the catalytically active Pt sites while suppressing the agglomeration of PtTe2 NSs. Upon thermal treatment, the resulting structures undergo partial phase transformation to PtTe along with the formation of Te vacancies within the PtTe2 lattice, generating PtTe/Te-vacancy-rich PtTe2 heterostructures. The combination of ultrathin morphology, defect engineering, and Pt-Te coordination enables efficient exposure and electronic modulation of Pt active centers, resulting in enhanced oxygen reduction activity with a mass activity of 1.22 A mgPt-1 and excellent durability. Overall, this work demonstrates that lattice-mismatch-driven epitaxial growth provides an effective strategy for constructing ultrathin NTMD architectures and for enhancing noble metal utilization through coordination and defect engineering.
The pervasive environmental presence of nano- and microplastics, particularly polystyrene nanoplastics (PSNPs), has raised increasing concern regarding their potential adverse effects on human health. While epithelial barrier impairment is recognized as a critical toxicological outcome, the oral epithelium remains a poorly understood target despite being the primary gateway for ingested nanoplastics. In this study, we demonstrate that PSNPs induce significant functional impairment of the oral barrier even under sub-cytotoxic conditions (>80% cell viability). Exposure of TR146 human buccal epithelial cell layers to PSNPs triggered an early increase in paracellular permeability (fluorescein isothiocyanate-labeled dextran (4 kDa) flux), followed by a decline in transepithelial electrical resistance. Crucially, these functional deficits occurred in the absence of overt cytotoxicity and were associated with the molecular downregulation and altered distribution of tight junction-related proteins, including ZO-2, occludin, MarvelD3, and claudin-3 and claudin-4. Our findings indicate that PSNP-induced alterations in TJ-related protein distribution may represent an early molecular event associated with oral epithelial barrier dysfunction under sub-cytotoxic conditions. Collectively, this study highlights the oral epithelium as a highly sensitive target and underscores that functional barrier failure, rather than direct cytotoxicity, may represent a key mechanism underlying nanoplastic-associated toxicity.
The oscillatory motion of graphene oxide-Go nanoparticles in water lubricating Maxwell nanofluid flow for heat and mass transfer enhancement in steady and fluctuating regime is important significance of this study. The aim of this work indicates the temperature distribution, nanoparticle concentration rate and velocity field around stretching radiating-cylinder in drilling systems. The nonlinear radiating energy, entropy generation, mixed convection, buoyancy ratio and oscillatory effects are assumed for heat and mass performance. The partial differential based mathematical expressions are developed to estimate the values of current analysis. The oscillatory stokes conditions, complex variables, and primitive transformations are applied to develop steady and fluctuating results. The computational outputs are secured using very efficient methods like finite difference and Gaussian elimination. The graphical outputs are displayed through TecPlot-360 and FORTRAN. The fluid velocity field, energy, and concentration outputs are executed with the help of various physical factors. The steady friction and steady thermal rate are depicted and are used in transient algorithm to depict the fluctuating friction rate and oscillatory thermal-mass transport. The magnitude of fluid velocity, fluid temperature and fluid concentration enhances as Maxwell parameter is enhanced. The variation in fluid velocity amplitude and fluid temperature increases as radiating energy is enhanced. For high parametric range of Maxwell number, the steady skin friction and mass transfer increases but heat transfer decreases. At smaller Eckert number, the oscillations in transient skin friction, transient heat and mass transfer are enhanced. At higher Maxwell parameter, buoyancy and Schmidt number, the large amplitude in heat and mass oscillations is observed.
Guiding synthetic nanomaterials toward specific cells and subcellular organelles remains a critical challenge for targeted therapeutics. Here, we report that ATPase-functionalized nanoparticles harness enzymatic turnover to autonomously navigate extracellular and intracellular ATP gradients, accumulating near cell surfaces, experiencing enhanced uptake, and once endocytosed, localizing selectively to mitochondria in both primary human aortic endothelial cells and HeLa cells. ATP depletion or ATPase inhibition abolishes accumulation and disrupts mitochondrial targeting, confirming the requirement for active enzymatic turnover. This targeting mechanism is preserved across particle types, including lipid-based vesicles, indicating broad applicability. This work establishes enzyme-powered chemotaxis as a route to pericellular accumulation, enhanced endocytosis, and organelle-specific delivery, providing a foundation for responsive nanomedicines targeting metabolically active disease environments. The strategy shifts the paradigm from passive, receptor-based delivery to dynamic, energy-responsive targeting.
Visualizing the combined toxic effects of micro(nano)plastics and heavy metal ions remains challenging due to the lack of suitable in situ imaging tools, and current co-exposure models are often simplified by simple mixing rather than using pre-formed complexes. In this work, a near-infrared biothiol fluorescent probe was developed based on a naphthalimide scaffold with an α,β-unsaturated acetyl group as a recognition site. The probe exhibits high sensitivity and selectivity toward biothiols, and the detection limit was determined to be 0.47 μM for Cys, 0.37 μM for GSH, and 0.95 μM for Hcy, respectively. This enables the monitoring of biothiol fluctuations in living cells and zebrafish. Using pre-formed PMMA-Hg2+ complexes as co-exposure pollutant models, we investigated nanoplastic-metal ion complex induced oxidative stress in living cells and zebrafish. Imaging results revealed that PMMA-Hg2+ complex co-exposure induces distinct biothiol fluctuation patterns compared to single exposure of PMMA or Hg2+. The surface charge alterations of complexes and lysosomal function were found to be involved in the process. This study provides visual evidence for elucidating the combined toxicity mechanisms of nanoplastic-heavy metal complex co-exposure.
Lyotropic liquid crystalline nanoparticles (LLCs) are promising nanocarriers for topical drug delivery due to their ability to enhance bioavailability and reduce systemic side effects. This study aimed to develop and evaluate a vorinostat-loaded LLCs gel for the treatment of psoriasis, to improve skin drug retention, therapeutic efficacy, and patient compliance. Vorinostat-loaded LLCs were prepared using glycerol monooleate as the lipid phase and Poloxamer 407 as a stabilizer. The nanoparticles were characterized for particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The LLCs were incorporated into a Carbopolbased gel and evaluated for in vitro drug release, skin permeation, and retention. In vivo efficacy was assessed in an imiquimod-induced psoriasis mouse model using PASI scoring, histopathology, and Ki-67 immunohistochemistry. The LLCs showed a particle size of 236.6 ± 7.05 nm, PDI of 0.27 ± 0.04, zeta potential of - 17.42 ± 0.28 mV, and entrapment efficiency of 81.65 ± 1.12%. Incorporation into gel enhanced skin drug retention by fourfold compared to plain vorinostat gel. The gel demonstrated sustained drug release up to 72 h without a burst effect. In vivo, vorinostat LLCs gel (0.05%) significantly reduced PASI scores, normalized histological features, and decreased Ki-67 expression compared to plain gel and marketed formulation. The enhanced therapeutic efficacy is due to the skin-lipid interactions of LLCs and their inherent hydrating properties, which together promote improved skin penetration, prolonged drug retention within the skin layers, and restoration of the skin barrier. Reduced systemic absorption further minimizes potential adverse effects, while the topical route ensures targeted delivery directly to psoriatic lesions. Vorinostat-loaded LLCs gel offers a stable, sustained-release, and skin-retentive formulation that significantly improves psoriasis treatment outcomes.
Spherical nucleic acids (SNAs) are examples of how nucleic acid structures can impact important biological functions. Herein, we explore how well-defined DNA nanostructures assembled on the surface of preformed SNAs can influence important processes like cellular uptake. Three different DNA nanostructures, which vary in clustering and/or topology, were studied with three different cell lines (NIH-3T3, HaCaT, RAW 264.7). All three structures exhibited higher cellular uptake than conventional SNAs, with one structure (TX motif SNA) exhibiting a 5-fold increase after 4 h of incubation. Increased DNA clustering and DNA crossover numbers correlate with enhanced Ca2+ binding and, ultimately, higher uptake primarily through clathrin- and macropinocytosis-mediated pathways (caveolae-mediated pathways have been observed with traditional ssSNAs). Ca2+ content within SNA structures facilitates uptake by making the structure less negatively charged and increasing interactions with Ca2+-binding proteins. This work shows how structural manipulation of the SNA shell can control and optimize its biological function.
Nanoconfined fluid is central to many engineering applications such as shale energy production, carbon sequestration, and molecular separations. While classical molecular dynamics (MD) simulation provides essential atomistic detail, its prohibitive computational cost severely limits accessible time and length scales. Hybrid MD-Monte Carlo (MDMC) methods accelerate sampling but lack generality beyond their trained conditions. In this work, we introduce an AI-assisted MDMC framework that overcomes this limitation by learning local, conditional transition statistics directly from MD trajectories. Our method encodes molecular motion into a compact set of neural network-predicted displacement actions, preserving MD-level accuracy within a drastically reduced dimensionality. This approach enables efficient sampling with robust generality. We systematically demonstrate the framework's accuracy and transferability across diverse thermodynamic conditions (temperature, pressure), spatial scales, and complex nano-scale geometries, establishing a versatile path for simulating confined fluid phenomena relevant to engineering applications.
Vanadium-based compounds are promising cathode materials for aqueous zinc-ion batteries (ZIBs), while the relatively poor high-rate performance, unstable long-term stability, and slow migration of Zn2+ ions have limited their practical applications. In this work, a sandwich-like stack of vanadium oxide-carbon nanobelts engineered with selenium defects (SL-V2O3/C-Se) was synthesized and used as a high-performance cathode for aqueous ZIBs. Taking advantage of the ordered and parallel arrangement of nanobelts with abundant selenium defects that facilitated the migration of the Zn2+ ion and electrolyte, SL-V2O3/C-Se exhibited rate performance and long-term stability much better than those of commercial V2O3 and V2O3/C without selenium doping. Even at a current density of 10 A g-1, SL-V2O3/C-Se exhibited a reversible capacity of 300 mAh g-1, which could retain 66% of its original capacity after 7000 cycles. This work provides an innovative approach to improve the capacity, long-term stability, and rate capability of electrode materials.
This study introduces highly sensitive, functionalized dialdehyde fullerene-like carbon nanostructures (DAFs) as a versatile platform for chemical sensing. The DAFs were synthesized through an effective functionalization strategy, confirmed by Fourier-Transform Infrared Spectroscopy (FTIR), which introduced key dialdehyde groups necessary for multi-modal detection. Transmission Electron Microscopy (TEM) validated a critical morphological evolution from small carbon dots (CDs) to larger, fullerene-shaped DAFs, providing a new electronic and structural foundation for sensing. The DAFs demonstrate dual sensing capabilities for both pH and non-polar organic vapors, specifically explosive cyclohexane (LEL ≈ 13000 ppm). The DAFs sensor's Limit of Detection (LOD) of 137.34 ppm is strategically justified by this hazard, as it provides an early, high-reliability safety warning significantly below the 10% LEL industrial safety threshold of 1300 ppm. Density Functional Theory (DFT) calculations elucidated the mechanism of gas detection, confirming that the interaction with non-polar cyclohexane fundamentally alters the electronic structure of the DAFs, causing the dipole moment (µ) to increase significantly from 5.060 Debye to 8.203 Debye, which underlies the observed fluorescence enhancement. Experimentally, the DAFs function as an effective pH probe, exhibiting a distinctive "turn-on" fluorescence response at alkaline pH 12 due to the deprotonation of surface functional groups. Crucially, the material operates as a simple, naked-eye visual sensor for cyclohexane, quantified by a clear shift in CIE chromaticity coordinates from (0.193, 0.422) to (0.209, 0.473) upon gas exposure. This work provides a deep, integrated theoretical and experimental understanding of functionalized carbon nanostructures for industrial safety and general environmental applications.
Understanding the behavior of electrocatalysts under operating conditions is essential to improving their performance. Electrochemical (scanning) transmission electron microscopy [EC-(S)TEM] enables real-time, high-resolution imaging of materials undergoing electrochemical processes; however, it provides limited information about the products of these processes in the solution phase, and the high-energy electron beam can perturb their distribution and reactivity through radiolysis. Previously, we demonstrated that Ni2+ not only enhances the electrocatalytic performance of Pt for the hydrogen evolution reaction (HER) but also, through Ni(OH)2 precipitation, that it serves as a quantitative in situ marker of HER activity at the single-nanoparticle level. Extending this quantitative footprinting methodology to EC-(S)TEM to report catalytic yield, we observe a different mechanism: while optical measurements indicate the expected Ni(OH)2 precipitation on the EC-(S)TEM chip, in situ EC-(S)TEM experiments reveal beam-induced reduction of Ni2+ to metallic Ni via radiolysis. Finite element modeling supports a mechanism involving H• intermediates and allows discrimination of the respective contributions of the HER and the electron beam. These results highlight the critical role of the beam in apparent electrocatalytic reactivity and provide a framework to quantify catalytic yields in EC-(S)TEM and to interpret operando data more cautiously.