Single-particle analysis of circulating bacterial extracellular vesicles reveals their biogenesis, changes in blood and links to intestinal barrier.

Bacterial extracellular vesicles (BEVs) are nano-size particles secreted by bacteria that carry various bioactive components. These vesicles are thought to provide a new window into the mechanisms by which bacteria affect their hosts, but their fundamental proprieties within human remain poorly understood. Here, we developed a single-vesicle analytical platform that enabled BEV detection in complex biological samples of host. Using this platform, we found the presence of BEVs in the host circulation and they were mainly derived from gut microbes. We showed that the levels of circulating BEVs in humans significantly increased with aging due to an age-related increase in intestinal permeability. Significantly different levels of BEVs in blood were also found in patients with colorectal cancer and colitis. Together, our study provides new insights into circulating BEV biology and reveals their potential as a new class of biomarkers.

Isolation and Purification of Bacterial Extracellular Vesicles from Human Feces Using Density Gradient Centrifugation.

Bacterial extracellular vesicles (BEVs) are nanovesicles derived from bacteria that play an active role in bacteria-bacteria and bacteria-host communication, transferring bioactive molecules such as proteins, lipids, and nucleic acids inherited from the parent bacteria. BEVs derived from the gut microbiota have effects within the gastrointestinal tract and can reach distant organs, resulting in significant implications for physiology and pathology. Theoretical investigations that explore the types, quantities, and roles of BEVs derived from human feces are crucial for understanding the secretion and function of BEVs from the gut microbiota. These investigations also necessitate an improvement in the current strategy for isolating and purifying BEVs. This study optimized the isolation and purification process of BEVs by establishing two density gradient centrifugation (DGC) modes: Top-down and Bottom-up. The enriched distribution of BEVs was determined in fractions 6 to 8 (F6-F8). The effectiveness of the approach was evaluated based on particle morphology, size, concentration, and protein content. The particle and protein recovery rates were calculated, and the presence of specific markers was analyzed to compare the recovery and purity of the two DGC modes. The results indicated that the Top-down centrifugation mode had lower contamination levels and achieved a recovery rate and purity similar to that of the Bottom-up mode. A centrifugation time of 7 h was sufficient to achieve a fecal BEV concentration of 108/mg. Apart from feces, this method could be applied to other body fluid types with proper modification according to the differences in components and viscosity. In conclusion, this detailed and reliable protocol would facilitate the standardized isolation and purification of BEVs and thus, lay a foundation for subsequent multi-omics analysis and functional experiments.

Isolation and Anticancer Progression Evaluation of the Chemical Constituents from Bridelia balansae Tutcher.

The dichloromethane extract of the roots of Bridelia balansae Tutcher (Phyllanthaceae) was found to show potential anticancer activity against HCT116 colorectal cancer cell. Our bioassay-guided phytochemical investigation of the roots of B. balansae led to the identification of 14 compounds including seven lignans (1-7), three phenylbenzene derivatives (8-10), two flavanone (11-12), and two triterpenoids (13-14). Among them, 4'-demethyl-4-deoxypodophyllotoxin (1) is the first aryltetralin lignan compound identified from this plant species. In addition, the stereochemistry of 1 was validated by X-ray crystallography for the first time, and its distinguished cytotoxic effect on HCT116 cells with an IC50 value at 20 nM was induced via an apoptosis induction mechanism. Compound 1 could also significantly decrease the migration rate of HCT116 cells, indicating its potential application against cancer metastasis. The western blot analysis showed that 1 has the potential to inhibit cell proliferation and metastasis. Treatment of 1 resulted in the downregulation of matrix metalloproteinases 2 (MMP2) and p-Akt, while p21 was upregulated. Collectively, the present study on the phytochemical and biological profile of B. balansae has determined the plant as a useful source to produce promising anticancer lead compounds.

Lactobacillus rhamnosus GG Regulates Host IFN-I Through the RIG-I Signalling Pathway to Inhibit Herpes Simplex Virus Type 2 Infection.

Numerous recent studies have demonstrated that the commensal microbiota plays an important role in host immunity against infections. During the infection process, viruses can exhibit substantial and close interactions with the commensal microbiota. However, the associated mechanism remains largely unknown. Therefore, in this study, we explored the specific mechanisms by which the commensal microbiota modulates host immunity against viral infections. We found that the expression levels of type I interferon (IFN-I) and antiviral priming were significantly downregulated following the depletion of the commensal microbiota due to treatment with broad-spectrum antibiotics (ABX). In addition, we confirmed a unique molecular mechanism underlying the induction of IFN-I mediated by the commensal microbiota. In vivo and in vitro experiments confirmed that Lactobacillus rhamnosus GG (LGG) can suppress herpes simplex virus type 2 (HSV-2) infection by inducing IFN-I expression via the retinoic acid-inducible gene-I (RIG-I) signalling pathway. Therefore, the commensal microbiota-induced production of IFN-I provides a potential therapeutic approach to combat viral infections. Altogether, understanding the complexity and the molecular aspects linking the commensal microbiota to health will help provide the basis for novel therapies already being developed.

Understanding ZIF particle chemical etching dynamics and morphology manipulation: in situ liquid phase electron microscopy and 3D electron tomography application.

In situ liquid phase transmission electron microscopy (TEM) and three-dimensional electron tomography are powerful tools for investigating the growth mechanism of MOFs and understanding the factors that influence their particle morphology. However, their combined application to the study of MOF etching dynamics is limited due to the challenges of the technique such as sample preparation, limited field of view, low electron density, and data analysis complexity. In this research, we present a study employing in situ liquid phase TEM to investigate the etching mechanism of colloidal zeolitic imidazolate framework (ZIF) nanoparticles. The etching process involves two distinct stages, resulting in the development of porous structures as well as partially and fully hollow morphologies. The etching process is induced by exposure to an acid solution, and both in situ and ex situ experiments demonstrate that the outer layer etches faster leading to overall volume shrinking (stage I) while the inner layer etches faster giving a hollow morphology (stage II), although both the outer layer and inner layer have been etched in the whole process. 3D electron tomography was used to quantify the properties of the hollow structures which show that the ZIF-67 crystal etching rate is larger than that of the ZIF-8 crystal at the same pH value. This study provides valuable insights into MOF particle morphology control and can lead to the development of novel MOF-based materials with tailored properties for various applications.

Extracellular vesicles derived from Akkermansia muciniphila promote placentation and mitigate preeclampsia in a mouse model.

Preeclampsia (PE) is a multisystem disorder with high maternal morbidity and mortality rates. Currently, no practical therapeutic approach is available to prevent PE progression, except for early delivery. Gut dysbiosis is associated with PE development. Previous data showed that the abundance of Akkermansia muciniphila (Am) was lower in patients with PE than in normotensive pregnant women. Here, in this study, decreased abundance of Am was observed in a PE mouse model. Also, we found that administration with Am could significantly attenuate systolic blood pressure, promote foetal growth and improve the placental pathology in mice with PE. Moreover, Am-derived extracellular vesicles (AmEVs) were transferred from the gastrointestinal (GI) tract to the placenta and mitigated pre-eclamptic symptoms in PE mice. These beneficial effects of AmEVs were mediated by enhanced trophoblast invasion of the spiral artery (SpA) and SpA remodelling through activation of the epidermal growth factor receptor (EGFR)-phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT) signalling pathway. Collectively, our findings revealed the potential benefit of using AmEVs for PE treatment and highlighted important host-microbiota interactions.

Direct Imaging of the Kinetic Crystallization Pathway: Simulation and Liquid-Phase Transmission Electron Microscopy Observations.

The crystallization of materials from a suspension determines the structure and function of the final product, and numerous pieces of evidence have pointed out that the classical crystallization pathway may not capture the whole picture of the crystallization pathways. However, visualizing the initial nucleation and further growth of a crystal at the nanoscale has been challenging due to the difficulties of imaging individual atoms or nanoparticles during the crystallization process in solution. Recent progress in nanoscale microscopy had tackled this problem by monitoring the dynamic structural evolution of crystallization in a liquid environment. In this review, we summarized several crystallization pathways captured by the liquid-phase transmission electron microscopy technique and compared the observations with computer simulation. Apart from the classical nucleation pathway, we highlight three nonclassical pathways that are both observed in experiments and computer simulations: formation of an amorphous cluster below the critical nucleus size, nucleation of the crystalline phase from an amorphous intermediate, and transition between multiple crystalline structures before achieving the final product. Among these pathways, we also highlight the similarities and differences between the experimental results of the crystallization of single nanocrystals from atoms and the assembly of a colloidal superlattice from a large number of colloidal nanoparticles. By comparing the experimental results with computer simulations, we point out the importance of theory and simulation in developing a mechanistic approach to facilitate the understanding of the crystallization pathway in experimental systems. We also discuss the challenges and future perspectives for investigating the crystallization pathways at the nanoscale with the development of in situ nanoscale imaging techniques and potential applications to the understanding of biomineralization and protein self-assembly.

Unravelling crystal growth of nanoparticles.

Crystal growth from nanoscale constituents is a ubiquitous phenomenon in biology, geology and materials science. Numerous studies have focused on understanding the onset of nucleation and on producing high-quality crystals by empirically sampling constituents with different attributes and varying the growth conditions. However, the kinetics of post-nucleation growth processes, an important determinant of crystal morphology and properties, have remained underexplored due to experimental challenges associated with real-space imaging at the nanoscale. Here we report the imaging of the crystal growth of nanoparticles of different shapes using liquid-phase transmission electron microscopy, resolving both lateral and perpendicular growth of crystal layers by tracking individual nanoparticles. We observe that these nanoscale systems exhibit layer-by-layer growth, typical of atomic crystallization, as well as rough growth prevalent in colloidal systems. Surprisingly, the lateral and perpendicular growth modes can be independently controlled, resulting in two mixed crystallization modes that, until now, have received only scant attention. Combining analytical considerations with molecular dynamics and kinetic Monte Carlo simulations, we develop a comprehensive framework for our observations, which are fundamentally determined by the size and shape of the building blocks. These insights unify the understanding of crystal growth across four orders of magnitude in particle size and suggest novel pathways to crystal engineering.

Membrane Protein Amuc_1100 Derived from Akkermansia muciniphila Facilitates Lipolysis and Browning via Activating the AC3/PKA/HSL Pathway.

Obesity, defined as a disorder of lipid metabolism caused by white fat accumulation, is closely related to the gut microbiota. Akkermansia muciniphila (Akk), one of the most common gut commensals, can reduce fat storage and promote the browning of white adipocytes, alleviating disorders of lipid metabolism. However, which components of Akk produce the effect remain unclear, limiting the application of Akk in the treatment of obesity. Here, we found that the membrane protein Amuc_1100 of Akk decreased formation of lipid droplets and fat accumulation during the differentiation process and stimulated browning in vivo and in vitro. Transcriptomics revealed that Amuc_1100 accelerated lipolysis through upregulation of the AC3/PKA/HSL pathway in 3T3-L1 preadipocytes. Quantitative PCR (qPCR) and Western blotting showed that Amuc_1100 intervention promotes steatolysis and browning of preadipocytes by increasing lipolysis-related genes (AC3/PKA/HSL) and brown adipocyte marker genes (PPARγ, UCP1, and PGC1α) at both the mRNA and protein levels. These findings introduce new insight into the effects of beneficial bacteria and provide new avenues for the treatment of obesity. IMPORTANCE An important intestinal bacterial strain Akkermansia muciniphila contributes to improving carbohydrate and lipid metabolism, thus alleviating obesity symptoms. Here, we find that the Akk membrane protein Amuc_1100 regulates lipid metabolism in 3T3-L1 preadipocytes. Amuc_1100 inhibits lipid adipogenesis and accumulation during the differentiation process of preadipocytes, upregulates the browning-related genes of preadipocytes, and promotes thermogenesis through activation of uncoupling protein-1 (UCP-1), including Acox1 involved in lipid oxidation. Amuc_1100 accelerates lipolysis via the AC3/PKA/HSL pathway, phosphorylating HSL at Ser 660. The experiments illustrated here identify the specific molecules and functional mechanisms of Akk. Therapeutic approaches with Amuc_1100 derived from Akk may help alleviate obesity and metabolic disorders.

Shedding light on neurons: optical approaches for neuromodulation.

Today's optical neuromodulation techniques are rapidly evolving, benefiting from advances in photonics, genetics and materials science. In this review, we provide an up-to-date overview of the latest optical approaches for neuromodulation. We begin with the physical principles and constraints underlying the interaction between light and neural tissue. We then present advances in optical neurotechnologies in seven modules: conventional optical fibers, multifunctional fibers, optical waveguides, light-emitting diodes, upconversion nanoparticles, optical neuromodulation based on the secondary effects of light, and unconventional light sources facilitated by ultrasound and magnetic fields. We conclude our review with an outlook on new methods and mechanisms that afford optical neuromodulation with minimal invasiveness and footprint.

Palette of Rechargeable Mechanoluminescent Fluids Produced by a Biomineral-Inspired Suppressed Dissolution Approach.

Mechanoluminescent materials, which emit light in response to mechanical stimuli, have recently been explored as promising candidates for photonic skins, remote optogenetics, and stress sensing. All mechanoluminescent materials reported thus far are bulk solids with micron-sized grains, and their light emission is only produced when fractured or deformed in bulk form. In contrast, mechanoluminescence has never been observed in liquids and colloidal solutions, thus limiting its biological application in living organisms. Here, we report the synthesis of mechanoluminescent fluids via a suppressed dissolution approach. We demonstrate that this approach yields stable colloidal solutions comprising mechanoluminescent nanocrystals with bright emissions in the range of 470-610 nm and diameters down to 20 nm. These colloidal solutions can be recharged and discharged repeatedly under photoexcitation and hydrodynamically focused ultrasound, respectively, thus yielding rechargeable mechanoluminescent fluids that can store photon energy in a reversible manner. This rechargeable fluid can facilitate a systemically delivered light source gated by tissue-penetrant ultrasound for biological applications that require light in the tissue, such as optogenetic stimulation in the brain.

High-Resolution Electron Tomography of Ultrathin Boerdijk-Coxeter-Bernal Nanowire Enabled by Superthin Metal Surface Coating.

The rapid advancement of transmission electron microscopy has resulted in revolutions in a variety of fields, including physics, chemistry, and materials science. With single-atom resolution, 3D information of each atom in nanoparticles is revealed, while 4D electron tomography is shown to capture the atomic structural kinetics in metal nanoparticles after phase transformation. Quantitative measurements of physical and chemical properties such as chemical coordination, defects, dislocation, and local strain have been made. However, due to the incompatibility of high dose rate with other ultrathin morphologies, such as nanowires, atomic electron tomography has been primarily limited to quasi-spherical nanoparticles. Herein, the 3D atomic structure of a complex core-shell nanowire composed of an ultrathin Boerdijk-Coxeter-Bernal (BCB) core nanowire and a noble metal thin layer shell deposited on the BCB nanowire surface is discovered. Furthermore, it is demonstrated that a new superthin noble metal layer deposition on an ultrathin BCB nanowire could mitigate electron beam damage using an in situ transmission electron microscope and atomic resolution electron tomography. The colloidal coating method developed for electron tomography can be broadly applied to protect the ultrathin nanomaterials from electron beam damage, benefiting both the advanced material characterizations and enabling fundamental in situ mechanistic studies.

A biomineral-inspired approach of synthesizing colloidal persistent phosphors as a multicolor, intravital light source.

Many in vivo biological techniques, such as fluorescence imaging, photodynamic therapy, and optogenetics, require light delivery into biological tissues. The limited tissue penetration of visible light discourages the use of external light sources and calls for the development of light sources that can be delivered in vivo. A promising material for internal light delivery is persistent phosphors; however, there is a scarcity of materials with strong persistent luminescence of visible light in a stable colloid to facilitate systemic delivery in vivo. Here, we used a bioinspired demineralization (BID) strategy to synthesize stable colloidal solutions of solid-state phosphors in the range of 470 to 650 nm and diameters down to 20 nm. The exceptional brightness of BID-produced colloids enables their utility as multicolor luminescent tags in vivo with favorable biocompatibility. Because of their stable dispersion in water, BID-produced nanophosphors can be delivered systemically, acting as an intravascular colloidal light source to internally excite genetically encoded fluorescent reporters within the mouse brain.

Pristine carbon nanotubes are efficient absorbers at radio frequencies.

Radio frequency ablation and microwave hyperthermia are powerful tools for destroying dysfunctional biological tissues. However, wireless application of these techniques is hindered by their inability to focus the electromagnetic energy to small targets. The use of locally injected radio frequency- or microwave-absorbing nanomaterials can help to overcome this challenge by confining heat production to the injected region. Previous theoretical work suggests that high-aspect-ratio conducting nanomaterials, such as carbon nanotubes, offer powerful radio frequency and microwave absorption. While carbon nanotubes have been demonstrated as radiothermal agents, common solubilization methods may reduce their absorption efficiency, yielding undesirable nonspecific heating in the biological tissue background. In this manuscript, we hypothesize that pristine carbon nanotubes can act as efficient absorbers at radio frequencies, thus providing differential heating over the tissue background. Specifically, we use a sonication-free preparation technique to preserve both the high aspect ratio and local concentration of pristine carbon nanotubes. We validate the differential heating of these samples by 4.5-fold at 2 GHz compared to the heating of saline at a physiological concentration using infrared thermography. In addition, we successfully achieved local heating of pristine carbon nanotubes within a three-dimensional biological tissue phantom. Numerical simulations further aid in producing a temperature map within the phantom and confirming localized heating. Due to their significant differential and local heating, we believe that pristine carbon nanotubes may facilitate region-specific radio frequency ablation and microwave hyperthermia while keeping nonspecific heating to a low level in the normal tissue background.

Tetrahedral framework nucleic acids linked CRISPR/Cas13a signal amplification system for rare tumor cell detection.

The sensitive and accurate detection of rare tumor cells provides precise diagnosis and dynamic assessment information in various tumor spectrums. However, rare tumor cells assay is still a challenge due to the exceedingly rare presence in the blood. In this research, we develop a fluorescent approach for the identification of rare tumor cells based on a combination of immunosorbent capture and a three-step signal amplification strategy. First, rare tumor cells are captured by immunoadsorption on 96-well plates. Second, self-synthesized tetrahedral framework nucleic acids (tFNAs) spontaneously anchor into the lipid bilayer of rare tumor cells, resulting in a "one to more" amplification effect. Then, the double-stranded DNA (dsDNA) binds to the vertices of the tFNAs and generates a large amount of target RNA by T7 polymerase, which is the secondary signal amplification. Finally, the target RNA activates the collateral cleavage ability of CRISPR/Cas13a, and the reporter RNA is cleaved for third signal amplification. The detection limit of the proposed method is down to 1 cell mL-1. Furthermore, the tFNAs-Cas13a system is also shown to be capable of detecting rare tumor cells in spiked-in samples and clinical blood samples. This platform enables speedy detection of rare tumor cells with high sensitivity and good specificity, and shows great potential for tumor diagnosis.

Mechanism and performance relevance of nanomorphogenesis in polyamide films revealed by quantitative 3D imaging and machine learning.

Biological morphogenesis has inspired many efficient strategies to diversify material structure and functionality using a fixed set of components. However, implementation of morphogenesis concepts to design soft nanomaterials is underexplored. Here, we study nanomorphogenesis in the form of the three-dimensional (3D) crumpling of polyamide membranes used for commercial molecular separation, through an unprecedented integration of electron tomography, reaction-diffusion theory, machine learning (ML), and liquid-phase atomic force microscopy. 3D tomograms show that the spatial arrangement of crumples scales with monomer concentrations in a form quantitatively consistent with a Turing instability. Membrane microenvironments quantified from the nanomorphologies of crumples are combined with the Spiegler-Kedem model to accurately predict methanol permeance. ML classifies vastly heterogeneous crumples into just four morphology groups, exhibiting distinct mechanical properties. Our work forges quantitative links between synthesis and performance in polymer thin films, which can be applicable to diverse soft nanomaterials.

Progress of carbon-based electrocatalysts for flexible zinc-air batteries in the past 5 years: recent strategies for design, synthesis and performance optimization.

The increasing popularity of wearable electronic devices has led to the rapid development of flexible energy conversion systems. Flexible rechargeable zinc-air batteries (ZABs) with high theoretical energy densities demonstrate significant potential as next-generation flexible energy devices that can be applied in wearable electronic products. The design of highly efficient and air-stable cathodes that can electrochemically catalyze both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are highly desirable but challenging. Flexible carbon-based catalysts for ORR/OER catalysis can be broadly categorized into two types: (i) self-supporting catalysts based on the in situ modification of flexible substrates; (ii) non-self-supporting catalysts based on surface coatings of flexible substrates. Methods used to optimize the catalytic performance include doping with atoms and regulation of the electronic structure and coordination environment. This review summarizes the most recently proposed strategies for the synthesis of designer carbon-based electrocatalysts and the optimization of their electrocatalytic performances in air electrodes. And we significantly focus on the analysis of the inherent active sites and their electrocatalytic mechanisms when applied as flexible ZABs catalysts. The findings of this review can assist in the design of more valuable carbon-based air electrodes and their corresponding flexible ZABs for application in wearable electronic devices.

Nanoscopic morphological effect on the optical properties of polymer-grafted gold polyhedra.

Plasmonic nanoparticles show highly sensitive optical properties upon local dielectric environment changes. Hybridisation of plasmonic nanoparticles with active polymeric materials can allow stimuli-responsive and multiplex sensing over conventional monotonic sensing capacity. Such heterogeneous adlayers around the plasmonic core component, however, are likely to perturb the local refractive index in the nanometre regime and lead to uncertainty in its intrinsic sensitivity. Herein we prepare a series of polystyrene-grafted polyhedral gold nanoparticles, cubic and concave cubic cores, with different edge lengths and polymer thicknesses with precise synthesis control. Their localised surface plasmon resonance (LSPR) spectral changes are monitored to understand the effect of core morphological details in the interplay of nanoscale polymeric shells. Quantitative image analysis of changes in the core and shell shape contours and finite-difference time-domain simulations of the corresponding LSPR spectra and electric field distributions reveal that the magnitude of the LSPR spectral shift is closely dependent on the core morphology, polymer shell thickness and electric field intensity. We also demonstrate that the polystyrene-grafted gold concave cube displays higher sensitivity for nanoscale refractive index change in the polymer shell than the polystyrene-grafted gold cube at different temperatures. Our systematic investigation will help design polymer-composited plasmonic nanosensors for desirable applications.

Differential heating of metal nanostructures at radio frequencies.

Nanoparticles with strong absorption of incident radio frequency (RF) or microwave irradiation are desirable for remote hyperthermia treatments. While controversy has surrounded the absorption properties of spherical metallic nanoparticles, other geometries such as prolate and oblate spheroids have not received sufficient attention for application in hyperthermia therapies. Here, we use the electrostatic approximation to calculate the relative absorption ratio of metallic nanoparticles in various biological tissues. We consider a broad parameter space, sweeping across frequencies from 1 MHz to 10 GHz, while also tuning the nanoparticle dimensions from spheres to high-aspect-ratio spheroids approximating nanowires and nanodiscs. We find that while spherical metallic nanoparticles do not offer differential heating in tissue, large absorption cross sections can be obtained from long prolate spheroids, while thin oblate spheroids offer minor potential for absorption. Our results suggest that metallic nanowires should be considered for RF- and microwave-based wireless hyperthermia treatments in many tissues going forward.

Machine Learning to Reveal Nanoparticle Dynamics from Liquid-Phase TEM Videos.

Liquid-phase transmission electron microscopy (TEM) has been recently applied to materials chemistry to gain fundamental understanding of various reaction and phase transition dynamics at nanometer resolution. However, quantitative extraction of physical and chemical parameters from the liquid-phase TEM videos remains bottlenecked by the lack of automated analysis methods compatible with the videos' high noisiness and spatial heterogeneity. Here, we integrate, for the first time, liquid-phase TEM imaging with our customized analysis framework based on a machine learning model called U-Net neural network. This combination is made possible by our workflow to generate simulated TEM images as the training data with well-defined ground truth. We apply this framework to three typical systems of colloidal nanoparticles, concerning their diffusion and interaction, reaction kinetics, and assembly dynamics, all resolved in real-time and real-space by liquid-phase TEM. A diversity of properties for differently shaped anisotropic nanoparticles are mapped, including the anisotropic interaction landscape of nanoprisms, curvature-dependent and staged etching profiles of nanorods, and an unexpected kinetic law of first-order chaining assembly of concave nanocubes. These systems representing properties at the nanoscale are otherwise experimentally inaccessible. Compared to the prevalent image segmentation methods, U-Net shows a superior capability to predict the position and shape boundary of nanoparticles from highly noisy and fluctuating background-a challenge common and sometimes inevitable in liquid-phase TEM videos. We expect our framework to push the potency of liquid-phase TEM to its full quantitative level and to shed insights, in high-throughput and statistically significant fashion, on the nanoscale dynamics of synthetic and biological nanomaterials.