Transmission Electron Microscopy Image Analysis Research Articles

Expanding the Diversity of Actinobacterial Tectiviridae: A Novel Genus from Microbacterium.

Six novel Microbacterium phages belonging to the Tectiviridae family were isolated using Microbacterium testaceum as a host. Phages MuffinTheCat, Badulia, DesireeRose, Bee17, SCoupsA, and LuzDeMundo were purified from environmental samples by students participating in the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) program at Alliance University, New York. The phages have linear dsDNA genomes 15,438-15,636 bp with 112-120 bp inverted terminal repeats. Transmission electron microscopy (TEM) imaging analysis revealed that the six novel phages have six-sided icosahedral double-layered capsids with an internal lipid membrane that occasionally forms protruding nanotubules. Annotation analysis determined that the novel Microbacterium phages all have 32-34 protein-coding genes and no tRNAs. Like other Tectiviridae, the phage genomes are arranged into two segments and include three highly conserved family genes that encode a DNA polymerase, double jelly-roll major capsid protein, and packaging ATPase. Although the novel bacteriophages have 91.6 to 97.5% nucleotide sequence similarity to each other, they are at most 58% similar to previously characterized Tectiviridae genera. Consequently, these novel Microbacterium phages expand the diversity of the Tectiviridae family, and we propose they form the sixth genus, Zetatectivirus.

Oral Curcumin through Mesoporous Silica Nanomaterials with Distinct Morphologies: Synthesis, Characterization, Biosafety Evaluation, and Antioxidant Activity In Vivo.

Antioxidant play a crucial role in the prevention and treatment of diseases associated with oxidative stress. Curcumin (CUR), as a natural antioxidant, exhibits numerous therapeutic properties, including antioxidant, anti-inflammatory, antibacterial, and antitumor activities. However, its limited bioavailability and poor water solubility hinder its application as an effective antioxidant. In this study, a series of mesoporous silica nanomaterials with distinct morphologies, i.e., mesoporous silica nanoparticles (MSN) and mesoporous silica nanorods (MSR) were synthesized by a template-sediment-etching method. CUR was selected as a model drug and encapsulated into these nanomaterials to improve its bioavailability in vivo. The morphology and size distribution of MSN and MSR were determined through transmission electron microscopy (TEM) imaging and Zetasizer analysis. Fourier transform infrared spectroscopy (FTIR) spectra confirmed the successful encapsulation of CUR within these nanomaterials. Furthermore, these CUR-loaded silica nanomaterials, denoted as CUR@MSN and CUR@MSR, exhibited excellent DPPH and ABTS free radical scavenging activity in vitro. Furthermore, CUR@MSN and CUR@MSR also exhibited obvious in vivo antioxidant activity. This study opens up new avenues for the development of enhanced antioxidants through the utilization of mesoporous silica nanomaterials.

DDDNet: A lightweight and robust deep learning model for accurate segmentation and analysis of TEM images

The primary aim of this study was to develop an optimal, lightweight model for the segmentation of transmission electron microscopy (TEM) images. Our model is designed with a minimal parameter count, superior performance metrics, and robust adaptability to variations in substrates, nanoparticle sizes, and nanomaterial diversity within TEM images. In achieving this, we benchmarked our model against four deep learning models using subsets from the Bright-Field TEM(BF-TEM) and Au-TEM datasets. Our model demonstrated exceptional segmentation performance, requiring only 0.34 M parameters and 39.33 G floating-point operations. It also provided the most accurate estimates of average nanoparticle sizes, closely matching true labeled values. These results confirm the model’s proficiency and precision in TEM image processing and introduce a powerful tool for nanoscale image analysis. Our work sets a new standard for lightweight and efficient TEM segmentation models, paving the way for future advancements in nanotechnology research.

Ethanolic Extract from Echinacea purpurea (L.) Moench Inhibits Influenza A/B and Respiratory Syncytial Virus Infection in vitro: Preventive Agent for Viral Respiratory Infections.

Among the most frequent causes of respiratory infections in humans are influenza A virus H1N1 (H1N1), influenza B virus (IVB), and respiratory syncytial virus (RSV). Echinacea is a perennial wildflower belonging to the Asteraceae family. Echinacea purpurea (L.) Moench is a species belonging to the Echinacea genus. Its characteristic compound, chicoric acid (CA), is known for its physiological activities, including antiviral effects and immune enhancement. Activities of E. purpurea 60% ethanol extract (EPE) and CA in inhibiting infections caused by H1N1, IVB, and RSV subtype A (RSV-A) were evaluated through plaque inhibition tests, quantification of viral gene expression, and analysis of transmission electron microscopy (TEM) images. Additionally, inhibitory activities of EPE and CA for hemagglutination and neuraminidase (NA) of H1N1 and IVB were determined. In the plaque reduction assays, both EPE and CA reduced infectivity against H1N1, IVB, and RSV-A. Furthermore, quantitative real-time polymerase chain reaction analysis revealed that EPE and CA reduced gene expression levels for H1N1, IVB, and RSV-A, whereas TEM image analysis confirmed their inhibitory effects on host cell infection by these viruses. Hemagglutination assays exhibited the ability of EPE and CA to hinder H1N1 and IVB attachment to host cell receptors. Furthermore, EPE and CA displayed inhibition activity against the NA of H1N1 and IVB. These findings suggest that EPE and CA can suppress the infection and propagation of H1N1, IVB, and RSV-A, demonstrating their potential as preventive and therapeutic agents for viral respiratory infections or as ingredients for health functional foods.

Microstructure of Gilsocarbon graphite revealed by a correlative study of optical texture and FIB-TEM

Transmission Electron Microscopy (TEM) alongside Polarized Optical Microscopy (POM), is used to investigate the microstructure of nuclear graphite, specifically Gilsocarbon coke, fillers, binders, and flour. Detailed analyses revealed domain structures, domain boundaries, sub-domains and two types of microcracks: intra-domain and inter-domain cracks. Analysis of TEM images, from samples prepared via Focused Ion Beam (FIB), showed domain sizes in coke filler and flour regions ranged from 1 to 3 μm, whereas binder regions had larger domains of up to tens of micrometers, with correspondingly longer Mrozowski cracks. Within these domains, sub-domain boundaries further constrained Mrozowski cracks, resulting in crack lengths significantly shorter than the domain size. Domain boundaries were classified into small-angle and large-angle boundaries based on orientation differences, with large-angle boundaries arising from multiple small-angle transformations facilitated by polygonal microcracks. This microstructural data obtained from virgin Gilsocarbon graphite provides essential inputs for an experimentally informed model predicting the deformation and fracture properties of this material at the micrometer length scale, which may offer improved insights to enhance our understanding of how these properties may evolve under reactor operating conditions.

Characterization of Mass, Diameter, Density, and Surface Properties of Colloidal Nanoparticles Enabled by Charge Detection Mass Spectrometry.

A variety of scattering-based, microscopy-based, and mobility-based methods are frequently used to probe the size distributions of colloidal nanoparticles with transmission electron microscopy (TEM) often considered to be the "gold standard". Charge detection mass spectrometry (CDMS) is an alternative method for nanoparticle characterization that can rapidly measure the mass and charge of individual nanoparticle ions with high accuracy. Two low polydispersity, ∼100 nm diameter nanoparticle size standards with different compositions (polymethyl methacrylate/polystyrene copolymer and 100% polystyrene) were characterized using both TEM and CDMS to explore the merits and complementary aspects of both methods. Mass and diameter distributions are rapidly obtained from CDMS measurements of thousands of individual ions of known spherical shape, requiring less time than TEM sample preparation and image analysis. TEM image-to-image variations resulted in a ∼1-2 nm range in the determined mean diameters whereas the CDMS mass precision of ∼1% in these experiments leads to a diameter uncertainty of just 0.3 nm. For the 100% polystyrene nanoparticles with known density, the CDMS and TEM particle diameter distributions were in excellent agreement. For the copolymer nanoparticles with unknown density, the diameter from TEM measurements combined with the mass from CDMS measurements enabled an accurate measurement of nanoparticle density. Differing extents of charging for the two nanoparticle standards measured by CDMS show that charging is sensitive to nanoparticle surface properties. A mixture of the two samples was separated based on their different extents of charging despite having overlapping mass distributions centered at 341.5 and 331.0 MDa.

In situ fabrication of atomically adjacent dual-vacancy sites for nearly 100% selective CH4 production

The photocatalytic CO2-to-CH4 conversion involves multiple consecutive proton-electron coupling transfer processes. Achieving high CH4 selectivity with satisfactory conversion efficiency remains challenging since the inefficient proton and electron delivery path results in sluggish proton-electron transfer kinetics. Herein, we propose the fabrication of atomically adjacent anion-cation vacancy as paired redox active sites that could maximally promote the proton- and electron-donating efficiency to simultaneously enhance the oxidation and reduction half-reactions, achieving higher photocatalytic CO2 reduction activity and CH4 selectivity. Taking TiO2 as a photocatalyst prototype, the operando electron paramagnetic resonance spectra, quasi in situ X-ray photoelectron spectroscopy measurements, and high-angle annular dark-field-scanning transmission electron microscopy image analysis prove that the VTi on TiO2 as initial sites can induce electron redistribution and facilitate the escape of the adjacent oxygen atom, thereby triggering the dynamic creation of atomically adjacent dual-vacancy sites during photocatalytic reactions. The dual-vacancy sites not only promote the proton- and electron-donating efficiency for CO2 activation and protonation but also modulate the coordination modes of surface-bound intermediate species, thus converting the endoergic protonation step to an exoergic reaction process and steering the CO2 reduction pathway toward CH4 production. As a result, these in situ created dual active sites enable nearly 100% CH4 selectivity and evolution rate of 19.4 μmol g-1 h-1, about 80 times higher than that of pristine TiO2. Thus, these insights into vacancy dynamics and structure-function relationship are valuable to atomic understanding and catalyst design for achieving highly selective catalysis.

TEM Image Analysis and Simulation Physics for Two-Step Recrystallization of Discretely Amorphized C3H5-Molecular-Ion-Implanted Silicon Substrate Surface

In this study, we investigate the initial rapid recrystallization of a discretely amorphized C3H5-molecular-ion-implanted silicon (Si) substrate surface in the subsequent thermal annealing treatment through the analysis of plan-view transmission electron microscopy (TEM) images and technology computer-aided design (TCAD) process simulation. In the approach of the analysis of the plan-view TEM image of the Si substrate surface, we found that initial rapid recrystallization occurs in the intermediate regions between the residual crystalline and discrete amorphous regions formed in the C3H5-molecular-ion-implanted Si substrate surface. In addition, the TCAD process simulation results indicate that the intermediate regions correspond to the amorphous pockets formed around the discrete amorphous regions in the C3H5-molecular-ion-implanted Si substrate surface and are recrystallized preferentially during the short thermal annealing time. These plan-view TEM image analysis and TCAD process simulation results reveal a two-step recrystallization of the discretely amorphized C3H5-molecular-ion-implaned Si substrate surface. After the initial rapid recrystallization of amorphous pockets in the 1st step, the recrystallization of discrete amorphous regions starts in the 2nd step. The incubation period between the 1st and 2nd steps is the time required to recrystallize the amorphous pockets around the discrete amorphous regions completely and redefine the amorphous/crystalline interface.

From silicon to silica: a green chemistry approach for hollow sphere nanoparticle formation.

Herein we report on an environmentally friendly and scalable production route for hollow silica spheres (HSSs). The process is based on close to 100% conversion of non-crystalline solid Si nanoparticles (D̄ = 40 ± 9 nm) in mild alkaline solutions (pH ≤ 9.0) at ambient temperature. The Si nanoparticles are prepared using the centrifugal chemical vapor deposition (cCVD) method. Combining transmission electron microscopy (TEM) imaging and nanoparticle size analysis with hydrogen evolution data, elemental mapping, and nitrogen adsorption for surface area measurement, we show for the first time experimental data that document a Kirkendall type Si-to-HSS formation process. Our understanding is that the Si nanoparticles exposed to air form a SiO2 film, which is stable in the mild alkaline environment. Silicon from the Si nanoparticles is transported through the thin SiO2 film and is reacting with H2O/OH- species on the particle surface or in the already thickened SiO2 shell to form silicic acid that in turn rapidly gets converted to a sol-gel to continue the growing of the silica shell. We foresee that this green chemistry approach can be utilized for HSS preparation for use in batteries, insulation materials and drug delivery.

Atomic-level characterization of η-twins with non-homogeneous nucleation on the E(Al18Mg3Cr2) phase in 7075 alloy: TEM observations and DFT calculations

In this work, an uncommon type of η-twin with non-homogeneous nucleation on the surface of the E-phase is characterized, and two defects and growth processes of the twin are analyzed. According to the transmission electron microscopy image analysis, heterogeneous nucleation of the η phase at the dominant site of the E phase can lead to the formation of such η-twin only when a rather strict site-direction relationship is satisfied as well as when it is at the interface adjacent to the E phase. The formation of twin defects is related to the E phase but ultimately determined by the nature of the η phase, and the crystallographic relationship between the defect structure and the E phase is self-consistent. Combined with the analytical results from STEM, first-principles calculations show that the solute segregation at the defects reduces the total energy of the system, which favors the transition of the η phase of the heterogeneous nucleation and the formation of twins, and that solute Al is more favorable than Mg. In addition, the elemental distribution and effects in the precipitation-free zone were analyzed by EDS mapping.

Valorization of nanocellulose from bael (Aegle marmelos correa) fruit waste shells: Surface chemistry and morphological analysis

In this work, the waste shells of bael (Aegle marmelos correa) were utilised as a source of cellulose nanocrystals (CNCs). The extracted CNCs were characterized using a series of characterization techniques. The Infrared spectroscopy technique is used for the synthesis process and chemical analysis. The X-ray diffraction peak deconvolution method (area method) shows the crystallinity index (C.I. %) of CNCs is 71 %, while 67 % by Segal's method (intensity method). The average diameter calculated by ImageJ software for AFM (Atomic force microscope) is 47.97 ± 2.50 nm while 23.25 ± 2.50 nm and 44.81 ± 2.50 nm from TEM (Transmission electron microscope) and SEM (Scanning electron microscope) image analysis. The zeta potential count of isolated CNC-BS is −25.72 mV, confirming the CNC-BS suspension's stability. Very good thermal stability (>225 °C) was confirmed by thermal analysis. The high specific surface area of cellulose nanocrystals (205.5 ± 0.20 m2/g) was confirmed by BET analysis.

Synthesis, characterization, and preliminary insights of ZnFe2O4 nanoparticles into potential applications, with a focus on gas sensing

This work presents a hydrothermal-based facile method for synthesizing ZnFe2O4, whose size can be controlled with the concentration of sodium acetate used as a fuel and its physical changes at nanoscales when exposed to two different gases. The structural, morphological, compositional, and electronic properties of the synthesized samples are also presented in this paper. The crystal structure of the synthesized samples was determined using an X-ray Diffractometer (XRD). The results revealed fluctuations in the size, lattice parameter, and strain in the nanoparticles with increasing the concentration of sodium acetate. Field-Emission Scanning Electron Microscopy (FESEM) was used to determine synthesized materials’ morphology and particle size. It revealed that the particles possessed approximately spherical morphology whose size decreased significantly with the increasing amount of sodium acetate. Transmission Electron Microscopy (TEM) was utilized to determine the structure, morphology, and elemental distributions in particles at the nanoscale, and it confirmed the findings of XRD and FESEM analyses. The high-resolution TEM (HRTEM) imaging analysis of the nanoparticles in our studied samples revealed that the particles predominantly possessed (001) type facets. X-ray photoelectron spectroscopy (XPS) and core-loss electron energy loss spectroscopy (EELS) showed an increasing fraction of Fe2+ with the decreasing size of the particles in samples. The Brunauer, Emmett, and Tellers (BET) analysis of samples revealed a higher surface area as the particle size decreases. In addition, the determined surface area and pore size values are compared with the literature, and it was found that the synthesized materials are promising for gas-sensing applications. The ab initio calculations of the Density of States (DOS) and Band structure of (001) surface terminating ZnFe2O4 were carried out using Quantum Espresso software to determine the bandgap of the synthesized samples. They were compared to their corresponding experimentally determined bandgap values and showed close agreement. Finally, in-situ TEM measurement was carried out on one of the four studied samples with robust properties using Ar and CO2 as reference and target gases, respectively. It is concluded from the presented study that the size reduction of the ZnFe2O4 nanoparticles (NPs) tunes the bandgap and provides more active sites due to a higher concentration of oxygen vacancies. The in-situ TEM showed us a nanoscale observation of the change in one of the crystal structure parameters. The d spacing of ZnFe2O4 NPs showed a noticeable fluctuation, reaching more than 5% upon exposure to CO2 and Ar gases.

Automated analysis of grain morphology in TEM images using convolutional neural network with CHAC algorithm

The shape and size of grains significantly impact the properties of polycrystalline materials. In particular, high temperature and radiation exposure in nuclear reactors can lead to considerable grain growth of UO2, thereby substantially modifying the fuel performance. Transmission electron microscopy (TEM) has been used to characterize the grain morphology of polycrystalline materials, but the manual analysis of TEM images is a time-consuming and labor-intensive process, which cannot meet the increasing demand for high-throughput data analytics.This study presents an automated approach we developed for characterizing grain morphology recorded in bright field TEM images during ion irradiations performed in situ. Our approach combines a machine learning model for detecting grain boundaries and a computer vision algorithm named CHAC for selecting well-labeled grains for statistical analysis. Using TEM images acquired from in-situ ion irradiation experiments on nanocrystalline UO2, we demonstrate that this automated approach can achieve comparable results to human experts while significantly reducing the analysis time. Moreover, the machine learning model functions as a "few-shot" model, requiring only a modest number of training images to perform effectively on a specific task. Consequently, researchers in need can efficiently train their own models following the procedures described in this study to automate grain morphology analysis of their own TEM images.

Synthesis and characterization of a novel magnetic chitosan–nickel ferrite nanocomposite for antibacterial and antioxidant properties

A novel nanomagnet modified with nickel ferrite nanoparticles (NPs) coated with hybrid chitosan (Cs–NiFe2O4) was synthesized using the co-precipitation method. The resulting nanomagnets were characterized using various techniques. The size of the nanomagnetic particles was estimated to be about 40 nm based on the transmission electron microscopy (TEM) image and X-ray diffraction analysis (XRD) pattern (using the Debye–Scherrer equation). Scanning electron microscopy (SEM) images indicated that the surface of Cs–NiFe2O4 NPs is flatter and smoother than the uncoated NiFe2O4 NPs. According to value stream mapping (VSM) analysis, the magnetization value of Cs–NiFe2O4 NPs (17.34 emu/g) was significantly lower than NiFe2O4 NPs (40.67 emu/g). The Cs–NiFe2O4 NPs indicated higher antibacterial properties than NiFe2O4 NPs and Cs. The minimum inhibitory concentrations of Cs–NiFe2O4 NPs against S. aureus and E. coli were 128 and 256 mg/mL, respectively. Antioxidant activity (evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging test) for NiFe2O4 NPs and Cs–NiFe2O4 NPs at the concentration of 100 µg/mL were 35% and 42%, respectively. Consequently, the synthesized Cs–NiFe2O4 NPs can be proposed as a viable material for biomedical applications.

Development and In Vitro Evaluation of Crizotinib-Loaded Lipid-Polymer Hybrid Nanoparticles Using Box-Behnken Design in Non-small Cell Lung Cancer.

The goal of the study was to produce, optimize, characterize, and compare crizotinib-loaded lipid-polymer hybrid nanoparticles (CL-LPHNPs), representing a novel contribution to the existing literature, and to determine their anticancer activity in non-small cell lung cancer cells (NSCLC). Box-Behnken design was used to investigate the effect of three independent variables: polymer amount (X1), soy phosphatidylcholine (X2), and DSPE-PEG (X3), on three responses: particle size (Y1), polydispersity index (Y2), and zeta potential (Y3). Different parameters were evaluated on the optimized LPHNP formulations such as encapsulation efficiency, drug release study, transmission electron microscopy (TEM) image analysis, and in vitro cell evaluations. The mean particle size of the optimized formulation is between 120 and 220 nm with a PDI<0.2 and a zeta potential of -10 to -15 mV. The encapsulation efficiency values of crizotinib-loaded PLGA-LPHNPs (CL-PLGA-LPHNPs) and crizotinib-loaded PCL-LPHNPs (CL-PCL-LPHNPs) were 79.25±0.07% and 70.93±1.81%, respectively. Drug release study of CL-PLGA-LPHNPs and CL-PCL-LPHNPs showed a controlled and sustained release pattern as a result of core-shell type. Additionally, after 48 h, CL-PLGA-LPHNPs and CL-PCL-LPHNPs significantly reduced the viability of NCI-H2228 cells compared to free crizotinib. Moreover, CL-PLGA-LPHNPs and CL-PCL-LPHNPs exhibited a significant decrease in RAS, RAF, MEK, and ERK gene/protein expression levels after 48-h incubation. In conclusion, this pioneering study introduces lipid-polymer hybrid nanoparticles containing crizotinib as a novel treatment approach, uniting the advantages of a polymeric core and a lipid shell. The successful formulation optimization using Box-Behnken design yielded nanoparticles with adjustable size, remarkable stability, high drug loading, and a customizable drug release profile. Extensive investigations of key parameters, including particle size, PDI, ZP, TEM analysis, drug release, EE%, and in vitro evaluations, validate the potential of these nanoparticles. Moreover, the examination of two different polymers, PLGA and PCL, highlights their distinct impacts on nanoparticle performance. This research opens up new prospects for advanced therapeutic interventions with lipid-polymer hybrid nanoparticles.

Nanocrystallization of Cu46Zr33.5Hf13.5Al7 Metallic Glass

The recently discovered Cu46Zr33.5Hf13.5Al7 (at.%) bulk metallic glass (BMG) presents the highest glass-forming ability (GFA) among all known copper-based alloys, with a record-breaking critical casting thickness (or diameter) of 28.5 mm. At present, much remains to be explored about this new BMG that holds exceptional promise for engineering applications. Here, we report our study on the crystallization behavior of this new BMG, using isochronal and isothermal differential scanning calorimetry (DSC), X-ray diffraction (XRD), and transmission electron microscopy (TEM). With the calorimetric data, we determine the apparent activation energy of crystallization, the Avrami exponent, and the lower branch of the isothermal time–temperature–transformation (TTT) diagram. With XRD and TEM, we identify primary and secondary crystal phases utilizing samples crystallized to different degrees within the calorimeter. We also estimate the number density, nucleation rate, and growth rate of the primary crystals through TEM image analysis. Our results reveal that the crystallization in this BMG has a high activation energy of ≈360 kJ/mole and that the primary crystallization of this BMG produces a high number density (≈1021 m−3 at 475 °C) of slowly growing (growth rate &lt; 0.5 nm/s at 475 °C) Cu10(Zr,Hf)7 nanocrystals dispersed in the glassy matrix, while the second crystallization event further produces a new phase, Cu(Zr,Hf)2. The results help us to understand the GFA and thermal stability of this new BMG and provide important guidance for its future engineering applications, including its usage as a precursor to glass–crystal composite or bulk nanocrystalline structures.

Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem Cells.

The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of MSCs, which can also affect the regenerative potential and immunological status of tissues. It is not known whether human herpes simplex viruses 1 and 2 (HSV1 and HSV2), well-known human pathogens that can cause lifelong infections, can induce changes in MSCs. In non-healing ulcers, HSV infection is known to affect deeper tissue layers. In addition, HSV infection can recur after initially successful cell therapies. Our aim was to study the response of adipose-derived MSCs (ADMSCs) to HSV infection in vitro. After confirming the phenotype and differentiation capacity of the isolated cells, we infected the cells in vitro with HSV1-KOS, HSV1-532 and HSV2 virus strains. Twenty-four hours after infection, we examined the gene expression of the cells via RNA-seq and RT-PCR; detected secreted cytokines via protein array; and determined autophagy via Western blot, transmission electron microscopy (TEM) and fluorescence microscopy. Infection with different HSV strains resulted in different gene-expression patterns. In addition to the activation of pathways characteristic of viral infections, distinct non-immunological pathways (autophagy, tissue regeneration and differentiation) were also activated according to analyses with QIAGEN Ingenuity Pathway Analysis, Kyoto Encyclopedia of Genes and Genome and Genome Ontology Enrichment. Viral infections increased autophagy, as confirmed via TEM image analysis, and also increased levels of the microtubule-associated protein light chain 3 (LC3B) II protein. We identified significantly altered accumulation for 16 cytokines involved in tissue regeneration and inflammation. Our studies demonstrated that HSV infection can alter the viability and immunological status of ADMSCs, which may have implications for ADMSC-based cell therapies. Alterations in autophagy can affect numerous processes in MSCs, including the inhibition of tissue regeneration as well as pathological differentiation.

Deep Learning-Based TEM Image Analysis for Fully Automated Detection of Gold Nanoparticles Internalized Within Tumor Cell.

Transmission electron microscopy (TEM) imaging can be used for detection/localization of gold nanoparticles (GNPs) within tumor cells. However, quantitative analysis of GNP-containing cellular TEM images typically relies on conventional/thresholding-based methods, which are manual, time-consuming, and prone to human errors. In this study, therefore, deep learning (DL)-based methods were developed for fully automated detection of GNPs from cellular TEM images. Several models of "you only look once (YOLO)" v5 were implemented, with a few adjustments to enhance the model's performance by applying the transfer learning approach, adjusting the size of the input image, and choosing the best optimization algorithm. Seventy-eight original (12,040 augmented) TEM images of GNP-laden tumor cells were used for model implementation and validation. A maximum F1 score (harmonic mean of the precision and recall) of 0.982 was achieved by the best-trained models, while mean average precision was 0.989 and 0.843 at 0.50 and 0.50-0.95 intersection over union threshold, respectively. These results suggested the developed DL-based approach was capable of precisely estimating the number/position of internalized GNPs from cellular TEM images. A novel DL-based TEM image analysis tool from this study will benefit research/development efforts on GNP-based cancer therapeutics, for example, by enabling the modeling of GNP-laden tumor cells using nanometer-resolution TEM images.

Atomic-Scale Polarization and Strain at the Surface of Lead Halide Perovskite Nanocrystals.

Inorganic halide perovskite nanocrystals (NCs) are being widely explored as next-generation optoelectronic materials. Critical to understanding the optoelectronic properties and stability behavior of perovskite NCs is the material's surface structure, where the local atomic configuration deviates from that of the bulk. Through low-dose aberration-corrected scanning transmission electron microscopy and quantitative imaging analysis techniques, we directly observed the atomic structure at the surface of the CsPbBr3 NCs. CsPbBr3 NCs are terminated by a Cs-Br plane, and the surface Cs-Cs bond length decreases significantly (∼5.6%) relative to the bulk, imposing compressive strain and inducing polarization, which we also observed in CsPbI3 NCs. Density functional theory calculations suggest such a reconstructed surface contributes to the separation of holes and electrons. These findings enhance our fundamental understanding of the atomic-scale structure, strain, and polarity at the surface of inorganic halide perovskites and provide valuable insights into designing stable and efficient optoelectronic devices.

Kinetic Modulation of Amyloid‐β (1‐42) Fibrillation and Alleviated Cytotoxicity with Rationally Designed Point Mutants

AbstractBackgroundMost Alzheimer’s disease (AD) treatments focus on symptomatic relief by boosting the availability of neurotransmitters in the brain. Aside from symptomatic therapies, the amyloid‐β (Aβ) targeting approach has recently been established to reduce or postpone the production of Aβ plaques.1 Therefore, understanding the pathogenesis of AD requires regulation of Aβ fibrillation.MethodWe used the CamSol method and molecular dynamics simulations to find a group of residues that were significantly associated with Aβ fibrillation. To investigate the suppressed amyloid aggregation and reduced cytotoxicity of the designed mutants, we performed multiple in vitro experiments such as thioflavin T assay, circular dichroism spectroscopy measurement, transmission electron microscopy image analysis, liquid chromatography‐mass spectrometry based quantification, and cell viability test. We also characterized structural dynamics of the designed mutants using a multidisciplinary biophysical approach with small‐angle X‐ray scattering, ion mobility‐mass spectrometry, additional in silico experiments, and mass spectrometry.ResultWe rationally designed mutant constructs to suppress the fibrillation process using comprehensive molecular dynamics simulations and the atomic resolution structure of fibrils. Then, we used a multidisciplinary biophysical technique to investigate the physicochemical characteristics and unveil the structural basis associated with reduced self‐assembly. Lastly, cell‐based tests were performed to evaluate the alleviated cytotoxicity of designed mutant candidates.ConclusionMore generally, our method for modulating the self‐assembly property of the pathologically disordered proteins offers a novel viewpoint to treating neurodegenerative diseases and other protein folding‐related issues.Reference:1. Sevigny, J., et al. “The antibody aducanumab reduces A beta plaques in Alzheimer’s disease.” Nature 2016, 537(7618), 50‐56.