Atomic Force Microscopy Research Articles

Determining structures of RNA conformers using AFM and deep neural networks.

Much of the human genome is transcribed into RNAs1, many of which contain structural elements that are important for their function. Such RNA molecules-including those that are structured and well-folded2-are conformationally heterogeneous and flexible, which is a prerequisite for function3,4, but this limits the applicability of methods such as NMR, crystallography and cryo-electron microscopy for structure elucidation. Moreover, owing to the lack of a large RNA structure database, and no clear correlation between sequence and structure, approaches such as AlphaFold5 for protein structure prediction do not apply to RNA. Therefore, determining the structures of heterogeneous RNAs remains an unmet challenge. Here we report holistic RNA structure determination method using atomic force microscopy, unsupervised machine learning and deep neural networks (HORNET), a novel method for determining three-dimensional topological structures of RNA using atomic force microscopy images of individual molecules in solution. Owing to the high signal-to-noise ratio of atomic force microscopy, this method is ideal for capturing structures of large RNA molecules in distinct conformations. In addition to six benchmark cases, we demonstrate the utility of HORNET by determining multiple heterogeneous structures of RNase P RNA and the HIV-1 Rev response element (RRE) RNA. Thus, our method addresses one of the major challenges in determining heterogeneous structures of large and flexible RNA molecules, and contributes to the fundamental understanding of RNA structural biology.

Improving Room Temperature Formaldehyde Sensitivity with Samarium-Doped Titanium Dioxide

Abstract Samarium (Sm)-doped titanium dioxide (TiO₂) thin films were synthesized using the spray pyrolysis technique at 400°C, with Sm doping concentrations of 0, 2, 4, and 6 Wt.% to enhance structural, optical, morphological, and gas-sensing properties. The films, deposited on ultrasonically cleaned glass substrates, were characterized using X-ray diffraction , scanning electron microscopy, atomic force microscopy (AFM), and UV-Vis spectroscopy. Structural analysis revealed improved crystallinity and uniform surface morphology with Sm doping, while AFM indicated increased surface roughness, promoting gas adsorption. UV-Vis analysis showed a reduced energy bandgap, enhancing visible light absorption and gas-sensing performance. Gas sensing evaluations demonstrated high sensitivity to formaldehyde, with notable selectivity over ethanol, toluene, and xylene at room conditions. The 6 Wt.% Sm-doped TiO₂ film exhibited the highest response (17.4), with a detection limit of 5 ppm, and fast response (23 s) and recovery (27 s) times. These properties underline the potential of Sm-doped TiO₂ films for efficient room-temperature gas sensors. Their enhanced sensitivity, selectivity, and stability suggest promising applications in environmental monitoring and air quality management, particularly for formaldehyde detection and volatile organic compound discrimination.

Ni-Co MOF Flowers/ZnO NRs Mediated Electrochemical Sensor for Rapid and Ultrasensitive Detection of Neotame in Food Samples

Abstract This study focuses on the bioreduction of waste-derived graphite rods into reduced graphene oxide(rGO), followed by the fabrication with Ni-Co metal-organic flowers and Zinc oxide nanorods(ZnO NRs) using Nafion, for sensitive detection of neotame. The Ni-Co metal-organic flowers and ZnO NRs were synthesized using solvothermal synthesis and Azadirachta indica leaf extract, respectively. Additionally, Nafion polymer enhances the stability and conductivity of the nanocomposite. The nanocomposite was characterized using UV-Vis, Fourier transform infrared spectorscopy, X-ray diffraction, Raman spectroscopy, dynamic light scattering, X-ray photoelectron spectroscopy, field-emission scanning electron microscopy, energy-dispersive X-ray analsysis, transmission electron microscopy, and atomic force microscopy. The electrochemical studies were carried out using electrochemical impedance spectroscopy and cyclic voltammetry. The modified electrode (rGO/Nafion/Ni-Co MOF/ZnO NRs) demonstrated improved electrochemical activity (34.01µA) for neotame with an enhanced peak current at +0.73V. The LOD and LOQ values were calculated and found to be 0.32 and 0.99 µM with a recovery (%) ranging from 94.50 to 101.34%. The outcome of this study identifies the morphological and electrochemical factors as major contributors to the adsorption affinities and catalytical activities, with promising possibilities for the design of electrochemical sensing of artificial sweeteners.

Enhancing Cu interconnect reflow in back-end-of-line metal wiring with ultrathin Co liners

Abstract This research investigates the gap-fill characteristics of Cu in back-end-of-line (BEOL) interconnects, focusing on Co liner deposition using chemical vapor deposition (CVD) and cyclic-CVD (C-CVD). Providing superior gap-fill characteristics for BEOL interconnect applications is important. Three methods—CVD, C-CVD, and a combination of the two—were compared in terms of their effects on Cu reflow and electrical performance. CVD exhibited the lowest resistivity (44 μΩ cm at 10 nm thickness) and the fewest carbon impurities, confirmed by time-of-flight secondary ion mass spectrometry (ToF-SIMS). Atomic force microscopy (AFM) revealed that CVD produced the smoothest surface (Rq ~0.5 nm), enabling better adhesion and uniform Cu reflow. At 300°C, Co liners deposited by CVD achieved void-free Cu–Mn filling in 20 nm trenches, which showed CVD to outperform other methods. These findings highlight CVD as the most effective technique for precise Co liner deposition, ensuring reliable Cu interconnects in advanced semiconductor nodes.


Photocatalytic Depolymerization of Lignin: C-O Bond Cleavage in β-O-4 Models Using S-Doped Ultra-Thin Bi3O4Cl Nanosheets

The selective depolymerization of β-O-4 lignin models into high-value aromatic monomers using photocatalysis presents both significant opportunities and challenges. Photocatalysts often face issues such as high photogenerated carrier recombination rates and limited operational lifetimes. This study introduces S doping to modulate the surface interface of Bi3O4Cl (BOC) nanosheets, enhancing C-O bond cleavage efficiency in β-O-4 lignin models under visible light at ambient temperatures. Comprehensive characterization, including atomic force microscopy (AFM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), electron spin resonance (ESR), and density functional theory (DFT) analysis, revealed that S doping reduces BOC nanosheet thickness to 1.51 nm and promotes charge carrier separation, thereby generating greater concentrations of reactive species, specifically •O2− and •OH. Photocatalytic depolymerization experiments demonstrated that S-doped BOC achieved a C-O bond cleavage selectivity of 93% and an aromatic monomer yield of 629.03 μmol/g/h (i.e., 1.5 times higher than that of undoped BOC). This work provides a strategic approach to designing photocatalysts with enhanced selectivity and efficiency for lignin depolymerization.

Investigating Dopant Effects in ZnO as an Electron Transport Layer for Enhanced Efficiency in Organic Photovoltaics

AbstractThe power conversion efficiencies of organic solar cells greatly depend on the device architecture and choice of charge transporting materials. Improved power conversion efficiency (PCE) for inverted organic solar cells is observed when using Sn‐doped ZnO as the electron transporting layer. By doping the elements with different numbers of valence electrons (Al3+ and Sn4+ ions) into the ZnO matrix, device conversion efficiencies of 8.69% and 9.21%, respectively, are achieved. Conductive atomic force microscopy (CAFM) observations reveal that the Sn‐doped ZnO film exhibits better conductivity due to its larger number of carrier charges. X‐ray photoemission spectroscopy (XPS) indicates larger oxygen vacancies (OV) in Sn‐doped ZnO. Electrochemical characterization exhibits that there is a reduction in series resistance and charge transfer (CT) resistance for SZO, indicating the optimal charge transport capability of the electron transport layer (ETL). Ultrafast time‐resolved studies further show that, in comparison with Al‐doped ZnO and un‐doped ZnO, the elevated carrier concentration in Sn‐doped ZnO plays a significant role in augmenting the photocurrent. Thus, it is determined how dopants in ETL influence CT mechanisms, enhancing the photovoltaic conversion efficiency, thus contributing to the development of cost‐effective and efficient photovoltaic technologies.

Why Mixed Halides in 2D Chiral Perovskites Weaken Chirality-Induced Spin Selectivity.

2D Ruddlesden-Popper (RP) perovskites, upon inclusion of a chiral amine, exhibit chirality-induced spin selectivity (CISS). Although alloying at the halogen site in MBA-based RPs (MBA: methylbenzylammonium) is one of the suitable routes to tune the CISS effect, the mixed-halide RP perovskites exhibited complete suppression of chirality when probed through circular dichroism (CD). Here, we present the CISS effect in a series of mixed-halide RP perovskites. We show that photoinduced halide segregation is the origin for the apparent chirality suppression. The spin-dependent charge transport was evidenced through magnetic-conducting atomic force microscopy (mc-AFM) studies and magnetoresistance (MR) measurements. The mc-AFM results show that in (R/S-MBA)2PbI4(1-x)Br4x, the CISS effect decreases with bromide inclusion, nonmonotonically; the microstrain developed in the lattice and the spin-polarized charge transport are found to be correlated. Such a behavior has been explained through an inhomogeneity in the strength of the hydrogen bond between the organic moieties and halogens in the inorganic framework of the compounds. Our results further inferred that the hydrogen-bond-induced coupling transfers the chirality from the amine to the inorganic sublattice. The work explains the weakened CISS effect in mixed-halide chiral RP perovskites and provides a strategy to tune the spin-polarized charge transport as well.

The conformational space of RNase P RNA in solution.

RNA conformational diversity has fundamental biological roles1-5, but direct visualization of its full conformational space in solution has not been possible using traditional biophysical techniques. Using solution atomic force microscopy, a deep neural network and statistical analyses, we show that the ribonuclease P (RNase P) RNA adopts heterogeneous conformations consisting of a conformationally invariant core and highly flexible peripheral structural elements that sample a broad conformational space, with amplitudes as large as 20-60 Å in a multitude of directions, with very low net energy cost. Increasing Mg2+ drives compaction and enhances enzymatic activity, probably by narrowing the conformational space. Moreover, analyses of the correlations and anticorrelations between spatial flexibility and sequence conservation suggest that the functional roles of both the structure and dynamics of key regions are embedded in the primary sequence. These findings reveal the structure-dynamics basis for the embodiment of both enzymatic precision and substrate promiscuity in the RNA component of the RNase P. Mapping the conformational space of the RNase P RNA demonstrates a new general approach to studying RNA structure and dynamics.

Copper Precursor-Driven Variations in Structural, Optical and Electrical Properties of SILAR-Deposited CTS Thin Films

Abstract This pioneering study elucidates, for the first time, the profound impact of copper precursors (copper acetate, copper sulfate, and copper chloride) on the structural, optical, and electrical properties of Copper Tin Sulfide (CTS) thin films synthesized via successive ionic layer adsorption and reaction (SILAR) deposition. Comprehensive characterization using X-ray diffraction (XRD), cross-sectional scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR) spectroscopy, and electrical and optical measurements revealed significant variations in crystallite size (59.3-76.4 nm), film thickness (1.235-4.75 µm), and conductance (3.7-6.4 × 10-11 S). Notably, copper chloride-derived films exhibited enhanced surface morphology, maximum bandgap energy (3.7 eV), and highest conductance, with displaying unique optical properties, including zero transmittance below 300 nm, low absorption above 300 nm, and a balanced absorption profile, making them ideal for photovoltaic cells, optical sensors, and UV-blocking applications. These results demonstrate the critical influence of copper precursors on CTS thin film properties, paving the way for tailored material design and enhanced device performance, with significant implications for the development of efficient and sustainable photovoltaic technologies.

Mesenchymal Stem Cell Plasticity: What Role Do Culture Conditions and Substrates Play in Shaping Biomechanical Signatures?

Cell functionality, driven by remarkable plasticity, is strongly influenced by mechanical forces that regulate mesenchymal stem cell (MSC) fate. This study explores the biomechanical properties of jaw periosteal cells (JPCs) and induced mesenchymal stem cells (iMSCs) under different culture conditions. We cultured both JPCs and iMSCs (n = 3) under normoxic and hypoxic environments, with and without osteogenic differentiation, and on laminin- or gelatin-coated substrates. Using atomic force microscopy, we measured cellular elasticity and Young’s modulus of calcium phosphate precipitates (CaPPs) formed under osteogenic conditions. Correlation analyses between cellular stiffness, quantity of CaPP deposition, and stiffness of formed CaPPs were evaluated. The results showed that iMSCs, despite their softer cellular consistency, tended to form CaPPs of higher elastic moduli than osteogenically differentiated JPCs. Particularly under normoxic conditions, JPCs formed stronger CaPPs with lower cellular stiffness profiles. Conversely, iMSCs cultivated under hypoxic conditions on laminin-coated surfaces produced stronger CaPPs while maintaining lower cellular stiffness. We conclude that JPCs and iMSCs display distinct biomechanical responses to culture conditions. While JPCs increase cellular stiffness during osteogenic differentiation, in particular under hypoxic conditions, iMSCs exhibit a decrease in stiffness, indicating a higher resistance to lower oxygen levels. In both cell types, a lower cellular stiffness profile correlates with enhanced mineralization, indicating that this biomechanical fingerprint serves as a critical marker for osteogenic differentiation.

Nano-spherical tip-based smoothing with minimal damage for 2D van der Waals heterostructures.

Two-dimensional materials and their heterostructures have significant potential for future developments in materials science and optoelectronics due to their unique properties. However, their fabrication and transfer process often introduce impurities and contaminants that degrade their intrinsic qualities. To address this issue, current atomic force microscopy (AFM) probe contact mode methods provide a solution by allowing in situ cleaning and real-time observation of the nanoscale cleaning process. Nevertheless, existing pyramidal probes may scratch surfaces and damage heterostructures during force application. Therefore, we proposed a method based on the nano-spherical probe contact mode to clean residual and polymer contamination for minimum damage cleaning of MoS2/hBN substrates. Comparative experiments with pyramidal probes in 2DM morphology and photoluminescence (PL) have shown that nano-spherical probes are exceptionally effective in cleaning bubbles of various sizes, compared to uncleaned MoS2, where PL full width at half maximum (FWHM) averages 0.115 eV, nano-spherical probes reduce it by 30% to 0.08 eV. Pyramidal probes, however, only clean smaller bubbles and leave residuals in larger ones, resulting in less optimal PL mapping data with values in both the 0.09 eV and 0.0115 eV regions. We also collected the standard deviation of the FWHM data points for the uncleaned region and the regions cleaned by the pyramidal and nano-spherical probes, which were 0.02773, 0.01895, and 0.00531, respectively. Notably, the standard deviation of the FWHM in the nano-spherical probe-cleaned region is only 28% of that in the pyramidal probe-cleaned region. Then, increasing the applied force leads to damage in the crystal structure, resulting in potential inconsistencies across different areas, as evidenced by KPFM and SEM observations. In contrast, nano-spherical probes demonstrate a uniform potential in KPFM and consistently maintain a smooth surface morphology in SEM throughout the process. This approach highlights the potential of nano-spherical probes to advance minimum-damage cleaning techniques in 2D material research and applications.

Enhanced Electrochemiluminescence by Knocking Out Gold Active Sites.

Electrochemiluminescence (ECL) of the conventional system of [Ru(bpy)3]2+ luminophore and amine-based coreactants is particularly inefficient on noble metal electrodes. This is due to the formation of a passivating oxide layer on the metal surface inhibiting the electro-oxidation of amines like tri-n-propylamine (TPrA) coreactant, Herein, we demonstrated the enhancement of ECL emission on gold surface by hydroxyl radicals attack that are chemically generated with Cu-Fenton reagent. These radicals selectively deactivate the gold active sites and knockout the metal surface asperities that counterintuitively led to an amplification of the ECL emission. Atomic Force Microscopy shows a massive smoothening of the surface. The electrochemical characterization proves that the involved ECL reaction mechanism switches from direct oxidation to catalytic route, where the kinetics of indirect TPrA oxidation is facilitated on deactivated gold surface. Besides, in situ smoothening of a rough electrode in presence of tandem [Ru(bpy)3]2+/TPrA, the ECL enhancement enables Cu2+ sensing with good reliability and limit of detection. Such atomically smoothened and corrosion-resistant gold surface readily tuned the ECL reactivity and opened new directions on influence of topography and reactivity on ECL mechanisms, thus will be extremely useful for the future development of ECL imaging strategies and highly sensitive ECL sensors.

PDMS—A simple and effective platform for determining Young's modulus of ultrathin 2D materials

Young's modulus plays a crucial role in determining the suitability of materials for various applications, including two-dimensional (2D) materials like graphene and transition metal dichalcogenides. Traditional indentation methods struggle with ultrathin 2D materials due to substrate effects. To overcome this, we propose using polydimethylsiloxane (PDMS) as a compliant substrate for atomic force microscopy force curves. This method, building on a 1950s analytical model, allows for accurate Young's modulus estimates by measuring flake thickness, applied force, and deformation. The results from our approach aligns well with existing literature for various 2D materials. PDMS, commonly used for mechanical exfoliation and transfer, offers an easily measurable Young's modulus, facilitating more efficient determinations. As the range of ultrathin materials grows, this platform enhances accessibility and efficiency in measuring Young's modulus, significantly contributing to the advancement of applications for these innovative materials.

Recent advances in research from plastic materials to microplastics

Plastics have become ubiquitous in our lives. Due to the ever-increasing population, rapid urbanization, and industrial advancement, the use of plastics has increased manifold. These plastic materials often disintegrate into microplastics (MPs) which are less than 5mm in size. MPs mostly enter aquatic habitats through improper waste management, illegal dumping, and unavoidable and unintentional discharges that take place during construction, manufacturing, farming, domestic consumption, and recreational activities. This review centers on exploring the origin, occurrence, and possible adverse effects of MPs on human well-being. Of the 485 literature reviewed for the study between 2014- 2023, 105 were found to be related to the MPs which were spread over 10 themes. The maximum number of papers were on sources of MPs, followed by MPs in freshwater ecosystems and waste management. The least number of literature was from the themes, transport of MPs and MPs in the soil environment. The literature was published mostly in China, India, Europe, and the Americas. Other countries like Australia, Latin America, Africa, and the Middle East contribute very little. The literature scan reveals that only 9% of all the generated plastic waste material is recycled, 12% is burned, and 79% of plastic litter is dumped in landfills and oceans. The dumped plastic settles and pollutes a variety of environmental matrices. MPs are intentionally manufactured to be added to personal care products that are washed down the drains through sewage or industrial wastewater. These MPs vary in density and colour, subject to the polymer type, and are present in varying sizes and concentrations in aquatic environments. The characterization of MPs originating from different types of polymer materials, in the reviewed literature, was performed based on the data obtained from Scanning Electron Microscopy Energy Dispersive Spectroscopy (SEM-EDS), Attenuated Total Reflection Fourier Transform Infra-Red spectroscopy (ATR-FTIR), Raman spectroscopy, and Atomic Force Microscopy (AFM). MPs have the potential to absorb harmful hydrophobic pollutants from the surroundings resulting in an indirect transfer of contaminants into the food web. Such MPs enter and affect humans, causing problems with the reproductive system, body weight, sex ratio, and live births. MPs pose a serious threat to organisms when ingested since they can obstruct the digestive tract, leading to oxidative and pathological stress, slowing down growth, and interfering with reproduction. Apart from the above, a comprehensive analysis of MP pollution, as well as its effect on human beings and the environment, has been discussed in terms of source identification and abundance. Also, has been discussed is a detailed review of the existing waste material recycled into new materials or reused without alteration or degradation to produce new energy sources. In the end, integrated strategies have been proposed to prevent the input of plastic waste material into the environment, by source control, improved plastic waste management, and techniques for degradation and conversion of MPs.

Noncontact Atomic Force Microscopy for Studying Biomolecules in Liquids

Noncontact Atomic Force Microscopy for Studying Biomolecules in Liquids

Platelets as key cells in endometriosis patients: Insights from small extracellular vesicles in peritoneal fluid and endometriotic lesions analysis.

Endometriosis is a chronic inflammatory condition characterized by the presence of endometrium-like tissue outside the uterus, primarily affecting pelvic organs and tissues. In this study, we explored platelet activation in endometriosis. We utilized the STRING database to analyze the functional interactions among proteins previously identified in small extracellular vesicles (EVs) isolated from the peritoneal fluid of endometriosis patients and controls. The bioinformatic analysis indicated enriched signaling pathways related to platelet activation, hemostasis, and neutrophil degranulation. Double immunohistochemistry analysis for CD61 and MPO revealed a significant presence of neutrophils and platelets in close contact infiltrating endometriotic lesions, suggesting potential cell-cell interactions. Subsequently, we isolated small EVs from the peritoneal fluid of women diagnosed with endometriosis and from women without endometriosis who underwent surgery for non-inflammatory benign diseases. We performed single-particle phenotyping analysis based on platelet biomarkers GPIIb/IIIa and PF4 using nanoflow cytometry, as well as single-particle morphological and nanomechanical characterization through atomic force microscopy. The study demonstrated that patients with endometriosis had a notably higher proportion of particles testing positive for platelet biomarkers compared to the total number of EVs. This finding implies a potential role for platelets in the pathogenesis of endometriosis. Further research is necessary to delve into the mechanisms underlying this phenomenon and its implications for disease progression.

Annealing Process-Induced Microstructural Variation in NiV/B4C Multilayers

The annealing process is one of the most common methods used to study the thermal stability of multilayers. To study the effect of the annealing process on the microstructural variation in NiV/B4C multilayers, different annealing experiments were performed on NiV/B4C multilayers with a d-spacing of 8 nm. This work provides a foundation for the fabrication of non-periodic NiV/B4C multilayers. The NiV/B4C multilayers were investigated by grazing-incidence X-ray reflectometry (GIXR), X-ray diffuse scattering (XRS), atomic force microscopy (AFM), X-ray diffraction (XRD), grazing-incidence small-angle X-ray scattering (GISAXS) and transmission electron microscopy (TEM). The temperature-dependent experiments showed that annealing at 70–290 °C slightly increased the period thickness and interface width. Annealing at higher temperatures resulted in significant structural changes and thickness ratio (Г = dNiV/d) changes from 0.4 to 1/3 at 340 °C. The time-dependent results showed that the microstructural variations primarily occurred after 60 min. The XRD, XRS, GISAXS and TEM were further used to study microstructural changes. It was found that the NiV/B4C multilayers exhibited a microcrystal structure after annealing, and that enhanced crystallinity and an increase in interface roughness were the main reasons for the microstructural changes.

MXene Nanoconfinement of SAM-Modified Molecularly Imprinted Electrochemical Biosensor for Point-of-Care Monitoring of Carcinoembryonic Antigen.

The high rate of cancer worldwide and the heavy costs imposed on governments and humanity have always motivated researchers to develop point-of-care (POC) biosensors for easy diagnosis and monitoring of cancer treatment. Herein, we report on a label-free impedimetric biosensor based on Ti3C2Tx MXene and imprinted ortho-phenylenediamine (o-PD) for the detection of carcinoembryonic antigen (CEA), a biomarker for various cancers surveillance, especially colorectal cancer (CRC). Accordingly, MXene was drop-casted on the surface of a disposable silver electrode to increase the sensitivity and create high-energy nanoareas on the surface, which are usable for protein immobilization and detection. A self-assembled monolayer (SAM) was exploited for oriented CEA immobilization on the MXene-modified electrode. The monomer-protein interaction and successful protein removal were confirmed by molecular docking and atomic force microscopy (AFM) investigations to evaluate the quality of the fabricated molecularly imprinted polymer (MIP). Also, the role of MXene in increasing the electrical field inside the nanoareas was simulated using COMSOL Multiphysics software. A suitable limit of detection (9.41 ng/mL), an appropriate linear range of detection (10 to 100 ng/mL) in human serum, and a short detection time (10 min) resulted from the use of SAM/MIP next to MXene. This biosensor presented outstanding repeatability (97.60%) and reproducibility (98.61%). Moreover, acceptable accuracy (between 93.04 and 116.04%) in clinical serum samples was obtained compared with immunoassay results, indicating the high potential of our biosensor for real sample analysis. This biomimetic and disposable sensor provides a cost-effective method for facile and POC monitoring of cancer patients during treatment.

Folic Acid-Targeted Mixed Pluronic Micelles for Delivery of Triptolide

The present study aimed to explore an ideal delivery system for triptolide (TPL) by utilizing the thin-film hydration method to prepare drug-loaded, folate-modified mixed pluronic micelles (FA–F-127/F-68–TPL). Scanning electron microscopy and atomic force microscopy showed that the drug-loaded micelles had a spherical shape with a small particle size, with an average of 30.7 nm. Cell viability experiments showed that FA–F-127/F-68–TPL significantly reduced HepG2 cell viability, exhibiting strong cytotoxicity. Its cytotoxicity was markedly enhanced compared with bare TPL. Nile red (Nr) was used as a model drug to prepare FA–F-127/F-68–Nr to further validate its tumor-targeting and cellular uptake capability. After coincubation with HepG2 cells, a multifunctional microplate reader showed that intracellular fluorescence intensity significantly increased, indicating that FA–F-127/F-68–Nr could more effectively enter the cells. A nude mouse model of subcutaneous hepatocellular carcinoma was constructed. Following tail vein injection of FA–F-127/F-68–Nr, the fluorescence imaging system showed that FA–F127/F-68–Nr could significantly target tumor tissue, and even if entering the small-sized tumor was challenging, it could be excreted through urine. Nude mice with subcutaneous hepatocellular carcinoma were treated with tail vein injections of FA–F-127/F-68–TPL (45 µg/kg) every other day for 21 days. The results showed that the growth of the transplanted tumors was significantly slowed, with no significant difference compared with bare TPL. In summary, the FA–F-127/F-68–TPL exhibits the advantages of low cost, excellent biological properties, active/passive targeting capabilities, notable cytotoxicity against liver cancer cells, and significant inhibition of transplanted hepatocellular carcinoma growth. Significantly, the FA–F-127/F-68–TPL, despite challenges in targeting tumors with an insignificant EPR effect, can be efficiently excreted via the kidneys, thereby preventing the release of the drug during prolonged circulation and potential damage to normal tissues. Therefore, FA–F-127/F-68–TPL represents a promising antitumor drug delivery system.

From viral assembly to host interaction: AFM's contributions to virology.

Viruses represent a diverse pool of obligate parasites that infect virtually every known organism, as such, their study is incredibly valuable for a range of fields including public health, medicine, agriculture, and ecology, and the development of biomedical technologies. Having evolved over millions of years, each virus has a unique and often complicated biology, that must be characterized on a case-by-case basis, even between strains of the same taxon. Owing to its nanoscale spatial resolution, atomic force microscopy (AFM) represents a powerful tool for exploring virus biology, including structural features, kinetics of binding to host cell ligands, virion self-assembly, and budding behaviors. Through the availability of numerous chemistries and advances in imaging modes, AFM is able to explore the complex web of host-virus interactions and life-cycle at a single virus level, exploring features at the level of individual bonds and molecules. Due to the wide array of techniques developed and data analysis approaches available, AFM can provide information that cannot be furnished by other modalities, especially at a single virus level. Here, we highlight the unique methods and information that can be obtained through the use of AFM, demonstrating both its utility and versatility in the study of viruses. As the technology continues to rapidly evolve, AFM is likely to remain an integral part of research, providing unique and important insight into many aspects of virology.