Recent uci_eng_cbe_oapdeposits items

Halide Ligands Control Optical and Chiroptical Response of DNA-Stabilized Ag28 Clusters in the Near-Infrared Region: Theoretical Prediction and Experimental Confirmation

Thu, 26 Mar 2026 00:00:00 +0000

Recent experiments [ Romolini ; Small Structures 2025, 2500022 ] uncovered the crystallographic structure of a near-infrared (NIR) emitting DNA-stabilized silver nanocluster, DNA2Ag28Cl2, which has two chloridos bound to the silver core. Here, we study the role of the halido in the cluster’s photophysical properties by replacing X = Cl with X = Br, I, H2O, or OH in a computational model for density functional theory (DFT) calculations. The calculations predict a systematic red shift of the NIR absorption and enhancement of a negative circular dichroism (CD) signal in the range of 810–860 nm when Cl, Br, and I are used as halide ligands, respectively. Leaving the two halido sites empty but coordinated by water molecules blue-shifts the linear absorption and CD signal from 810 nm and dramatically switches the CD sign. The explanations for this behavior are found by a detailed analysis of the electronic structure and the impact of the X ligands to the frontier orbitals. We directly...

A nanoporous capacitive electrochemical ratchet for continuous ion separations

Wed, 25 Mar 2026 00:00:00 +0000

Directed ion transport in liquid electrolyte solutions underlies many phenomena in natural and industrial settings. While nature has evolved structures that drive continuous ion flow without Faradaic redox reactions, establishing this process in synthetic systems has been challenging. Here we report an ion pump that drives aqueous ions against a force using a capacitive ratchet mechanism independent of redox reactions. Modulation of an electric potential between thin metallic layers on either face of a nanoporous alumina wafer immersed in solution results in persistent voltages and ionic currents. This occurs due to the nonlinear capacitive nature of electric double layers, whose repeated charging and discharging sustains a continuous ion flux. Using this approach, we demonstrate ratchet-driven electrodialysis that reaches a 50% decrease in the conductivity of the solution in a dilution cell. These ratchet-based ion pumps can enable continuous desalination and selective ion separation...

Gerischer Electrochemistry Today

Fri, 13 Mar 2026 00:00:00 +0000

Semiconductor photoelectrochemistry is a dynamic and interdisciplinary field at the forefront of research in solar fuels, energy conversion, and catalysis. This Perspective captures the collective insights from the second Gerischer Electrochemistry Today Symposium, held at Colorado State University in Fort Collins, CO, in August 2024, which convened leading researchers, early-career scientists, and industry partners to define the critical next steps for the field. Through interactive sessions, technical talks, panel discussions, and training initiativesincluding a Semiconductor Electrochemistry Bootcampthe symposium emphasized three pillars of advancement: (i) facilitating the exchange of new ideas in semiconductor electrochemistry and charge separation; (ii) fostering the development of future researchers, research topics, and participation in the semiconductor workforce; and (iii) building community. This Energy Focus distills key themes from the meeting and identifies major...

Effect of cell compression on the performance and the structure of proton exchange membrane water electrolyzer (PEMWE) assembly

Thu, 12 Mar 2026 00:00:00 +0000

In the field of water electrolysis, the proton exchange membrane water electrolyzer (PEMWE) is currently the most advanced technology for producing hydrogen without emitting CO2. Although PEMWE plants are already in operation, further research is needed to improve cell efficiency and reduce the use of rare materials, such as iridium oxide catalysts for the oxygen evolution reaction (OER). One of the main causes of performance loss in PEMWE is the relatively low electric conductivity of the porous transport layer (PTL) and of the anode catalyst layer, which results in ohmic losses and low catalyst utilization during high current density operation. The objective of this study is to investigate how optimization of the PTL and electrode interface can increase the cell performance. To this end, we tested different cell assemblies using fibrous and sintered PTLs, decreasing membrane thickness, reducing iridium loading, and inserting a microporous layer to increase contact surface area....

Xeno-nucleic acids support formation of Ag(I)-mediated duplexes and silver nanoclusters

Thu, 12 Mar 2026 00:00:00 +0000

The expanded backbone chemistries of xeno-nucleic acids (XNAs) hold significant promise for emerging areas of synthetic biology and nanomaterials, but metal-mediated XNA interactions remain largely unexplored. Here, we use a combination of circular dichroism spectroscopy and mass spectrometry to show that XNAs can form Ag+-mediated duplex structures resembling their DNA counterparts. XNAs with a range of different backbone compositions are found to stabilize photoluminescent silver nanoclusters with spectral properties that can be tuned based on their respective backbone chemistry. The resistance of silver nanoclusters to nuclease digestion is also compared for DNA and XNAs. These results show that XNA backbone chemistry provides a new tool beyond nucleobase sequence for controlling and expanding the properties of nucleic acid-stabilized silver nanoclusters and metal-mediated DNA duplexes.

Using X-ray radiography to study oxygen flow in a proton exchange membrane electrolyzer operating under balanced pressure conditions

Wed, 11 Mar 2026 00:00:00 +0000

Of the various water electrolyzer technologies, the proton exchange membrane electrolyzer (PEMWE) is one of the best solutions for producing clean hydrogen without releasing CO2. In order to allow for widespread use of clean hydrogen, it is necessary to decrease its cost, which is intrinsically related to system operation. Current PEMWE plants operate in differential mode, directly pressurizing hydrogen and benefiting from thermodynamic compression, which increases overall system efficiency. However, high differential pressure above 30 bar can cause membrane stress, resulting in membrane creeping and failure. Pressurizing the water and operating at balanced pressure allows hydrogen to be produced at higher pressures while preserving the integrity of the membrane and porous layers. Nevertheless, the impact of pressurizing water on PEMWE performance must be better understood to maximize performance under balanced pressure conditions. This study examined the impact of water...

Synergizing Chemical and AI Communities for Advancing Laboratories of the Future

Thu, 12 Feb 2026 00:00:00 +0000

The development of automated experimental facilities and the digitization of experimental data have introduced numerous opportunities to radically advance chemical laboratories. As many laboratory tasks involve predicting and understanding previously unknown chemical relationships, machine learning (ML) approaches trained on experimental data can substantially accelerate the conventional design-build-test-learn process. This outlook article aims to help chemists understand and begin to adopt ML predictive models for a variety of laboratory tasks, including experimental design, synthesis optimization, and materials characterization. Furthermore, this article introduces how artificial intelligence (AI) agents based on large language models can help researchers acquire background knowledge in chemical or data science and accelerate various aspects of the discovery process. We present three case studies in distinct areas to illustrate how ML models and AI agents can be leveraged to...

Unlocking Two‐Photon Chiral Signatures in DNA‐Stabilized Silver Nanoclusters: Two‐Photon Circular Dichroism and Circularly Polarized Luminescence

Thu, 12 Feb 2026 00:00:00 +0000

ABSTRACT Near‐infrared (NIR) emitters with chiroptical properties are a novel class of materials with significant promise for chiral sensing and optoelectronic applications. Chiral nanoparticles, in particular, offer distinct advantages over molecular chiral agents. However, their practical applications remain significantly hindered due to challenges to precisely control nanoparticle chirality and reduce heterogeneity. Here, we investigate one‐photon (1P) and two‐photon (2P) chiroptical properties of DNA‐stabilized silver nanoclusters (DNA‐Ag N ) as atomically defined, water‐soluble chiral nanoprobes. We perform a detailed analysis of 1P and 2P circular dichroism (1P‐CD and 2P‐CD, respectively) and circularly polarized luminescence (CPL) of (DNA) 2 [Ag 16 Cl 2 ] 8+ , a NIR emissive DNA‐Ag N with solved crystal structure, over a broad wavelength range. We observe that (DNA) 2 [Ag 16 Cl 2 ] 8+ exhibits 2P‐CD two orders of magnitude higher than 1P anisotropy factor, with additional...

Foundation Models for Zero-Shot Segmentation of Scientific Images without AI-Ready Data

Fri, 2 Jan 2026 00:00:00 +0000

Zero-shot and prompt-based models have excelled at visual reasoning tasks by leveraging large-scale natural image corpora, but they often fail on sparse and domain-specific scientific image data. We introduce Zenesis, a no-code interactive computer vision platform designed to reduce data readiness bottlenecks in scientific imaging workflows. Zenesis integrates lightweight multimodal adaptation for zero-shot inference on raw scientific data, human-in-the-loop refinement, and heuristic-based temporal enhancement. We validate our approach on Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) datasets of catalyst-loaded membranes. Zenesis outperforms baselines, achieving an average accuracy of 0.947, Intersection over Union (IoU) of 0.858, and Dice score of 0.923 on amorphous catalyst samples; and 0.987 accuracy, 0.857 IoU, and 0.923 Dice on crystalline samples. These results represent a significant performance gain over conventional methods such as Otsu thresholding and standalone...

Physical model and experimental validation of a high temperature proton exchange membrane electrochemical hydrogen pump cell for efficient single-stage extraction of low concentration hydrogen gas

Tue, 16 Dec 2025 00:00:00 +0000

There is interest in valorization of existing natural gas infrastructure to facilitate the co-transportation of hydrogen via blending of hydrogen gas initially at limited concentrations of 1–20 vol% H2 and to subsequently extract hydrogen at fuel cell quality standards (SAE J2719/ISO14687-2). High temperature proton exchange membrane electrochemical hydrogen pump (HT-PEM EHP) based on phosphoric acid doped polybenzimidazole (PA-PBI) exhibits good performance at elevated temperatures (>120 °C), which provides desirable tolerance to non-methane natural gas constituents that are problematic for lower temperature based EHP. To better understand the suitability of the HT-PEM EHP for such gas separation processes, a two-dimensional model of EHP based on PA-PBI was developed. The model is validated for several relevant operating conditions and across cells with differing amounts of phosphoric acid content in the electrodes. Operando micro x-ray computed tomography (CT) imaging...

Triel-Defined Helicity in One-Dimensional III–VI–VII van der Waals Crystals

Tue, 16 Dec 2025 00:00:00 +0000

Inorganic extended lattice solids that bear complex helical motifs manifest unusual physical and quantum states that arise due to their noncentrosymmetric or chiral nature. However, the systematic understanding of how elemental composition influences the structure and physical properties in helical inorganic crystals has been precluded by the rarity of these materials and the lack of modular phases that display such motifs. Here, we report the synthesis of AlSeI single crystals, the first aluminum-containing helical crystal in the III-VI-VII 1D van der Waals class. AlSeI completes the experimentally accessible triel series in the helical selene iodides alongside InSeI and GaSeI. Using the Al, Ga, and In triel series in this selene iodide class, we experimentally demonstrate the evolution of the local quasi-tetrahedral building unit geometry, chain packing, helical parameters, and band gaps based primarily on the identity of the triel atom. Our results underscore the chemical modularity...

Surface Charge in Electrical Double Layer as a Kinetic Descriptor of Electrocatalytic Reactions

Mon, 15 Dec 2025 00:00:00 +0000

The successful commercialization of electrochemical energy-conversion systems hinges on a deeper understanding of electrocatalytic reaction kinetics. Despite extensive research, a key descriptor that characterizes electrolyte effects on reaction kinetics remains elusive. Here, surface charge in electrical double layers (EDLs) is introduced as a descriptor for electrolyte-dependent kinetics. The surface charge is calculated with a continuum EDL model parameterized by density-functional theory. The model is validated by reproducing the anomalously low slope of Pt(111) in Parsons-Zobel plots. Strong correlations are observed between calculated surface charge and experimental kinetic currents for hydrogen evolution, oxygen reduction, and CO2-reduction reactions across various pH levels and cationic species. These correlations can be either promotional or inhibitory, depending on solute-intermediate interactions. In acidic media, incorporating adsorbate charge captures specific adsorption...

Simulating Ambient Pressure X-Ray Photoelectron Spectroscopy with Electric Double Layer-Informed Continuum Models

Thu, 11 Dec 2025 00:00:00 +0000

The Electric Double Layer (EDL) governs charge-transfer processes upon its formation at an electrode/electrolyte interface, thereby critically influencing electrochemical performance in energy conversion technologies. Challenges in experimentally measuring the EDL properties arise from its nanometer-scale structure and dynamics, as well as distinguishing overlapping influences from various interfacial phenomena. Addressing the latter, Shibata et al. proposed a parameter-fitting-free continuum model of the EDL that accounts for microscopic interactions. Additionally, Favaro et al. observed broadening of the acquired signal in ambient pressure X-ray photoelectron spectroscopy (APXPS), attributed to the potential drop across the electrical double layer (EDL). The aim of this study is to develop mathematical continuum models to elucidate the connection between the structure of the EDL and results from photoelectron spectroscopy measurements. This framework utilizes continuum models...

Complementary biomolecular coassemblies direct energy transport for cardiac photostimulators

Wed, 8 Oct 2025 00:00:00 +0000

Charge and energy transport within living systems are fundamental processes that enable the autonomous function of excitable cells and tissues. To date, localized control of these transport processes has been enabled by genetic modification approaches to render light sensitivity to cells. Here, we present peptidic nanoassemblies as constituents of a cardiac biomaterial platform that leverages complementary sequence interactions to direct photoinduced energy transport at the cellular interface. Photophysical characterizations and conductivity measurements confirm the occurrence of energy/charge transfer and photocurrent generation upon optical excitation in both dry and electrolytic environments. Comparing an electrostatic sequence pair against a sequence-matched donor-acceptor coassembly, we demonstrate that the sequence design with charge complementarity shows more prominent photocurrent behavior. With the flanking bioadhesive units, the primary and stem cell-derived cardiomyocytes...

Enhancing water and oxygen transport through electrode engineering for AEM water electrolyzers

Tue, 9 Sep 2025 00:00:00 +0000

Anion-exchange membrane water electrolyzers (AEMWEs) can accelerate the deployment of more efficient and affordable hydrogen production solutions. Here, electrode structure is shown to affect water back-diffusion and oxygen transport, which, in return, governs overpotential behaviors in AEMWEs. Measurements indicate that electrode with copious catalytic sites produces water close to the AEM, creating a higher water gradient and driving water back-diffusion, which improves membrane hydration and mass transport. In situ measurement reveals a high pH gradient near the anode surface, which affects anode kinetics. Operando measurement shows reduced oxygen accumulation when decoupling oxygen production and transport on anode. Catalyst ink rheology and stability are tuned with additives to realize scalable fabrication of electrodes with enhanced transport features, allowing AEMWE to operate at 2 A cm−2 for over 1,000+ h at a 2.3 μV h−1 degradation rate. Analysis during and post-durability...

Anion-Exchange-Membrane Electrolysis with Alkali-Free Water Feed

Mon, 8 Sep 2025 00:00:00 +0000

Hydrogen is a green and sustainable energy vector that can facilitate the large-scale integration of intermittent renewable energy, renewable fuels for heavy transport, and deep decarbonization of hard-to-abate industries. Anion-exchange-membrane water electrolyzers (AEM-WEs) have several achieved or expected competitive advantages over other electrolysis technologies, including the use of precious metal-free electrocatalysts at both electrodes, fluorine-free hydrocarbon-based ionomeric membranes and bipolar plates based on inexpensive materials. Contrasting the analogous proton-exchange-membrane system (PEM-WE), where pure water is circulated (no support electrolyte), the current generation of AEM-WEs necessitates the circulation of a dilute aqueous alkaline electrolyte for reaching high energy efficiency and durability. For several reasons, including but not limited to lower cost of balance-of-plant, lower operating cost and improved device's lifetime, achieving high cell efficiency...

PyRESP: A flexible program for polarizable force field parameterizations

Wed, 13 Aug 2025 00:00:00 +0000

PyRESP: A flexible program for polarizable force field parameterizations

Ion Transport at Polymer–Argyrodite Interfaces

Wed, 30 Jul 2025 00:00:00 +0000

Solid-state electrolytes, particularly polymer/ceramic composite electrolytes, are emerging as promising candidates for lithium-ion batteries due to their high ionic conductivity and mechanical flexibility. The interfaces that arise between the inorganic and organic materials in these composites play a crucial role in ion transport mechanisms. While lithium ions are proposed to diffuse across or parallel to the interface, few studies have directly examined the quantitative impact of these pathways on ion transport and little is known about how they affect the overall conductivity. Here, we present an atomistic study of lithium-ion (Li⁺) transport across well-defined polymer-argyrodite interfaces. We present a force field for polymer-argyrodite interfacial systems, and we carry out molecular dynamics and enhanced sampling simulations of several composite systems, including poly(ethylene oxide) (PEO)/Li₆PS₅Cl, hydrogenated nitrile butadiene rubber...

Precision Synthesis of a Single Chain Polymorph of a 2D Solid within Single‐Walled Carbon Nanotubes

Wed, 30 Jul 2025 00:00:00 +0000

The discovery and synthesis of atomically precise low-dimensional inorganic materials have led to numerous unusual structural motifs and nascent physical properties. However, access to low-dimensional van der Waals (vdW)-bound analogs of bulk crystals is often limited by chemical considerations arising from structural factors like atomic radii, bonding or coordination, and electronegativity. Using single-walled carbon nanotubes (SWCNTs) as confinement templates, we demonstrate the synthesis of a short-wave infrared-absorbing quasi-1D (q-1D) chain polymorph of Sb₂Te₃ ([Sb₄Te₆]_n) that is structurally and electronically distinct from its 2D counterpart. It is found that the q-1D chain polymorph has both three- and five-coordinate Sb atoms covalently bonded to Te and is thermodynamically stabilized by the electrostatic interaction between the encapsulated chain and the model SWCNT. The complementary experimental and computational...

The origin and control of interstitial impurities in refractory complex concentrated alloys

Wed, 30 Jul 2025 00:00:00 +0000

Interstitial impurities, primarily O and N, inadvertently introduced during the processing of refractory complex concentrated alloys (RCCAs) significantly limit the mechanical properties of the alloys at room temperature. Plasma arc melting (PAM) has facilitated the quest for RCCAs, showcasing remarkable combinations of strength and ductility. In this work, the composition and chemistry of residual gases in the PAM chamber environment during arc melting and the interstitial impurities in elemental feedstocks were analyzed to quantify the origin of O and N during synthesis. Moreover, the thermodynamic mechanisms governing the origin of interstitial impurities in arc-melted MoNbTaW RCCAs were discussed. With an understanding of the mechanisms governing the content of interstitial impurities in RCCAs during PAM, arc-melted MoNbTaW RCCAs with fewer than 100 ppm O were synthesized. The arc-melted MoNbTaW RCCAs were then characterized using electron microscopy and atom probe tomography...

Non‐Uniform Electric Field Manipulation of Chromogenic Peptide Amphiphile Assemblies

Tue, 29 Jul 2025 00:00:00 +0000

This work investigates the influence of dielectrophoretic forces on the structural features and the resulting aggregates of a chromogenic model system, peptide-diacetylene (D₃GV-DA) amphiphiles. Here, we systematically investigate how non-uniform electric fields impact the (i) peptide-directed supramolecular assembly stage and (ii) topochemical photopolymerization stage of polydiacetylenes (PDAs) in a quadrupole-based dielectrophoresis (DEP) device, as well as the (iii) manipulation of D₃GV-DA aggregates in a light-induced DEP (LiDEP) platform. The conformation-dependent chromatic phases of peptide-PDAs are utilized to probe the chain-level effect of DEP exposure after the supramolecular assembly or after the topochemical photopolymerization stage. Steady-state spectroscopic and microscopy analyses show that structural features such as the chirality and morphologies of peptidic 1-D nanostructures are mostly conserved upon DEP exposure, but applying mild,...

Selective Induction of Molecular Assembly to Tissue‐Level Anisotropy on Peptide‐Based Optoelectronic Cardiac Biointerfaces

Tue, 29 Jul 2025 00:00:00 +0000

The conduction efficiency of ions in excitable tissues and of charged species in organic conjugated materials both benefit from having ordered domains and anisotropic pathways. In this study, a photocurrent-generating cardiac biointerface is presented, particularly for investigating the sensitivity of cardiomyocytes to geometrically comply to biomacromolecular cues differentially assembled on a conductive nanogrooved substrate. Through a polymeric surface-templated approach, photoconductive substrates with symmetric peptide-quaterthiophene (4T)-peptide units assembled as 1D nanostructures on nanoimprinted polyalkylthiophene (P3HT) surface are developed. The 4T-based peptides studied here can form 1D nanostructures on prepatterned polyalkylthiophene substrates, as directed by hydrogen bonding, aromatic interactions between 4T and P3HT, and physical confinement on the nanogrooves. It is observed that smaller 4T-peptide units that can achieve a higher degree of assembly order within...

Light-triggered cardiac microphysiological model

Tue, 29 Jul 2025 00:00:00 +0000

Light is recognized as an accurate and noninvasive tool for stimulating excitable cells. Here, we report on a non-genetic approach based on organic molecular phototransducers that allows wiring- and electrode-free tissue modulation. As a proof of concept, we show photostimulation of an in vitro cardiac microphysiological model mediated by an amphiphilic azobenzene compound that preferentially dwells in the cell membrane. Exploiting this optical based stimulation technology could be a disruptive approach for highly resolved cardiac tissue stimulation.

Concentration-Driven Assembly and Sol–Gel Transition of π‑Conjugated Oligopeptides

Tue, 29 Jul 2025 00:00:00 +0000

Advances in supramolecular assembly have enabled the design and synthesis of functional materials with well-defined structures across multiple length scales. Biopolymer-synthetic hybrid materials can assemble into supramolecular structures with a broad range of structural and functional diversity through precisely controlled noncovalent interactions between subunits. Despite recent progress, there is a need to understand the mechanisms underlying the assembly of biohybrid/synthetic molecular building blocks, which ultimately control the emergent properties of hierarchical assemblies. In this work, we study the concentration-driven self-assembly and gelation of π-conjugated synthetic oligopeptides containing different π-conjugated cores (quaterthiophene and perylene diimide) using a combination of particle tracking microrheology, confocal fluorescence microscopy, optical spectroscopy, and electron microscopy. Our results show that π-conjugated oligopeptides self-assemble into β-sheet-rich...

Energy transfer within responsive pi-conjugated coassembled peptide-based nanostructures in aqueous environments

Tue, 29 Jul 2025 00:00:00 +0000

Steady-state and time-resolved photophysical measurements demonstrate energy transfer within π-conjugated peptide nanostructures composed of oligo-(p-phenylenevinylene)-based donor units and quaterthiophene-based acceptor units in completely aqueous environments. These peptide-based assemblies encourage energy migration along the stacking axis, thus resulting in the quenching of donor emission peaks along with the development of new spectral features reminiscent of acceptor emission. These spectral changes were observed even at minute amounts of the acceptor (starting at 1 mol%), suggesting that exciton migration is involved in energy transport and supporting a funnel-like energy transduction mechanism. The reversibility of nanostructure formation and the associated photophysical responses under different conditions (pH, temperature) were also studied. This unique material design incorporates two different semiconducting units coassembled within peptide nanostructures and...

Endothelial extracellular vesicles contain protective proteins and rescue ischemia-reperfusion injury in a human heart-on-chip

Tue, 29 Jul 2025 00:00:00 +0000

Extracellular vesicles (EVs) derived from various stem cell sources induce cardioprotective effects during ischemia-reperfusion injury (IRI). These have been attributed mainly to the antiapoptotic, proangiogenic, microRNA (miRNA) cargo within the stem cell-derived EVs. However, the mechanisms of EV-mediated endothelial signaling to cardiomyocytes, as well as their therapeutic potential toward ischemic myocardial injury, are not clear. EV content beyond miRNA that may contribute to cardioprotection has not been fully illuminated. This study characterized the protein cargo of human vascular endothelial EVs (EEVs) to identify lead cardioactive proteins and assessed the effect of EEVs on human laminar cardiac tissues (hlCTs) exposed to IRI. We mapped the protein content of human vascular EEVs and identified proteins that were previously associated with cellular metabolism, redox state, and calcium handling, among other processes. Analysis of the protein landscape of human cardiomyocytes...

Looking both ways: Electroactive biomaterials with bidirectional implications for dynamic cell–material crosstalk

Tue, 29 Jul 2025 00:00:00 +0000

Cells exist in natural, dynamic microenvironmental niches that facilitate biological responses to external physicochemical cues such as mechanical and electrical stimuli. For excitable cells, exogenous electrical cues are of interest due to their ability to stimulate or regulate cellular behavior via cascade signaling involving ion channels, gap junctions, and integrin receptors across the membrane. In recent years, conductive biomaterials have been demonstrated to influence or record these electrosensitive biological processes whereby the primary design criterion is to achieve seamless cell-material integration. As such, currently available bioelectronic materials are predominantly engineered toward achieving high-performing devices while maintaining the ability to recapitulate the local excitable cell/tissue microenvironment. However, such reports rarely address the dynamic signal coupling or exchange that occurs at the biotic-abiotic interface, as well as the distinction between...

Mussel-inspired 3D fiber scaffolds for heart-on-a-chip toxicity studies of engineered nanomaterials

Tue, 29 Jul 2025 00:00:00 +0000

Due to the unique physicochemical properties exhibited by materials with nanoscale dimensions, there is currently a continuous increase in the number of engineered nanomaterials (ENMs) used in consumer goods. However, several reports associate ENM exposure to negative health outcomes such as cardiovascular diseases. Therefore, understanding the pathological consequences of ENM exposure represents an important challenge, requiring model systems that can provide mechanistic insights across different levels of ENM-based toxicity. To achieve this, we developed a mussel-inspired 3D microphysiological system (MPS) to measure cardiac contractility in the presence of ENMs. While multiple cardiac MPS have been reported as alternatives to in vivo testing, most systems only partially recapitulate the native extracellular matrix (ECM) structure. Here, we show how adhesive and aligned polydopamine (PDA)/polycaprolactone (PCL) nanofiber can be used to emulate the 3D native ECM environment of...

Biomimetic and estrogenic fibers promote tissue repair in mice and human skin via estrogen receptor β

Tue, 29 Jul 2025 00:00:00 +0000

The dynamic changes in estrogen levels throughout aging and during the menstrual cycle influence wound healing. Elevated estrogen levels during the pre-ovulation phase accelerate tissue repair, whereas reduced estrogen levels in post-menopausal women lead to slow healing. Although previous reports have shown that estrogen may potentiate healing by triggering the estrogen receptor (ER)-β signaling pathway, its binding to ER-α has been associated with severe collateral effects and has therefore limited its use as a therapeutic agent. To this end, soy phytoestrogens, which preferentially bind to the ER-β, are currently being explored as a safer therapeutic alternative to estrogen. However, the development and evaluation of phytoestrogen-based materials as local ER-β modulators remains largely unexplored. Here, we engineered biomimetic and estrogenic nanofiber wound dressings built from soy protein isolate (SPI) and hyaluronic acid (HA) using immersion rotary jet spinning. These engineered...

Cooperative β-sheet coassembly controls intermolecular orientation of amphiphilic peptide-polydiacetylene conjugates

Tue, 29 Jul 2025 00:00:00 +0000

In this work, we elucidated the structural organization of stimuli-responsive peptide-polydiacetylene (PDA) conjugates that can self-assemble as 1D nanostructures under neutral aqueous conditions. The amino acid sequences bear positively or negatively charged domains at the periphery of the peptide segments to promote solubility in water while also driving assembly of the individual and combined components into β-sheets. The photopolymerization of PDA, as well as the sensitivity of the resulting optical properties of the polymeric material to external stimuli, highly depends on the structural organization of the assembly of amphiphilic peptide-diacetylene units into 1D-nanostructures. Solid-state NMR measurements on ¹³C-labeled and ¹⁵N-labeled samples show that positively charged and negatively charged peptide amphiphiles are each capable of self-assembly, but self-assembly favors antiparallel β-sheet structure. When positively and negatively charged peptide...

Micropatterning Photoconductive Peptide Assemblies on Stiff and Soft Biomaterial Substrates

Tue, 29 Jul 2025 00:00:00 +0000

The propagation of electrical signals in the human heart relies on organized conduction pathways to optimally function and pump blood into the rest of the body. Mimicking this directionality across interconnected myocytes in vitro is currently achieved by patterning the cells themselves, which are often subjected to external stimulatory cues that are rarely localized or have controlled anisotropy. Here, we demonstrate an approach to interface micropatterned optoelectronic peptides with cardiomyocytes, whereby the engineered biomolecular structures dictate the organization of cells in a substrate, while also presenting photocurrent-generating electrodes of defined microscale geometries. To this end, we utilized surface modification strategies that allowed for the creation of stable micropatterns of quaterthiophene-bearing peptide assemblies on both glass (∼GPa range) and gelatin hydrogel (∼20 kPa) substrates that last for multiple days within an aqueous environment. The...

Human brain microvascular endothelial cell pairs model tissue-level blood–brain barrier function

Tue, 29 Jul 2025 00:00:00 +0000

The blood-brain barrier plays a critical role in delivering oxygen and nutrients to the brain while preventing the transport of neurotoxins. Predicting the ability of potential therapeutics and neurotoxicants to modulate brain barrier function remains a challenge due to limited spatial resolution and geometric constraints offered by existing in vitro models. Using soft lithography to control the shape of microvascular tissues, we predicted blood-brain barrier permeability states based on structural changes in human brain endothelial cells. We quantified morphological differences in nuclear, junction, and cytoskeletal proteins that influence, or indicate, barrier permeability. We established a correlation between brain endothelial cell pair structure and permeability by treating cell pairs and tissues with known cytoskeleton-modulating agents, including a Rho activator, a Rho inhibitor, and a cyclic adenosine monophosphate analog. Using this approach, we found that high-permeability...

Levelized cost and carbon intensity of solar hydrogen production via water splitting using a scalable and intrinsically safe photocatalytic Z-scheme raceway system

Tue, 22 Jul 2025 00:00:00 +0000

Schematic of photocatalytic type 2 Z-scheme raceway design with hydrogen reactor cylinders floating on an oxygen reactor raceway pool. The raceway concept enables a scalable, low-cost, and low-carbon intensity method of hydrogen production. Generating hydrogen from local energy resources such as solar or wind would unlock a low-carbon energy carrier that could be used to reduce greenhouse gas emissions in sectors such as industry and transportation. Yet, the allocation of new or existing power generation solely to hydrogen production remains contentious due to disputes regarding emissions accounting. Photocatalytic (PC) hydrogen production technologies offer a unique solution, as hydrogen is produced directly from solar energy and water, without the need for electricity generation. However, cost projections for all photocatalytic designs to date have suggested that they are not cost competitive compared to conventional electrolysis systems manufactured at scale. Herein, we offer...

Proton Exchange Membrane (PEM) Water Electrolysis: Cell-Level Considerations for Gigawatt-Scale Deployment

Thu, 10 Jul 2025 00:00:00 +0000

Hydrogen produced with no greenhouse gas emissions is termed "green hydrogen" and will be essential to reaching decarbonization targets set forth by nearly every country as per the Paris Agreement. Proton exchange membrane water electrolyzers (PEMWEs) are expected to contribute substantially to the green hydrogen market. However, PEMWE market penetration is insignificant, accounting for less than a gigawatt of global capacity. Achieving substantive decarbonization via green hydrogen will require PEMWEs to reach capacities of hundreds of gigawatts by 2030. This paper serves as an overarching roadmap for cell-level improvements necessary for gigawatt-scale PEMWE deployment, with insights from three well-established hydrogen technology companies included. Analyses will be presented for economies of scale, renewable energy prices, government policies, accelerated stress tests, and component-specific improvements.

Structured light imaging mesoscopy: detection of embedded morphological changes in superficial tissues

Mon, 30 Jun 2025 00:00:00 +0000

Significance

Current paradigms for the optical characterization of layered tissues involve explicit consideration of an inverse problem which is often ill-posed and whose resolution may retain significant uncertainty. Here, we present an alternative approach, structured light imaging mesoscopy (SLIM), that leverages the inherent sensitivity of raw spatial frequency domain (SFD) reflectance measurements for the detection of embedded subsurface scattering changes in tissue.

Aim

We identify wavelength-spatial frequency ( λ-fx ) combinations that provide optimal sensitivity of SFD reflectance changes originating from scattering changes in an embedded tissue layer. We specifically consider the effects of scattering changes in the superficial dermis which is a key locus of pathology for diverse skin conditions such as cancer, aging, and scleroderma.

Approach

We used Monte Carlo simulations in a four-layer skin model to analyze the SFD reflectance changes resulting...

Structured light imaging mesoscopy for detection of embedded morphological changes in superficial tissues

Mon, 30 Jun 2025 00:00:00 +0000

This study introduces Structured Light Imaging Mesoscopy (SLIM), a novel non-contact optical method for detecting subsurface morphological tissue alterations. By leveraging the inherent sensitivity of spatial frequency domain (SFD) reflectance measurements, SLIM identifies specific wavelength-spatial frequency combinations that optimize the detection of scattering changes in the superficial dermis, a key area for various skin conditions. Monte Carlo simulations across a range of skin tones revealed that these optimal combinations vary with melanin concentration. Specifically, in subjects with lighter skin tones optimal sensitivity is achieved using shorter wavelengths and higher spatial frequencies, while for darker skin tones longer wavelengths and lower spatial frequencies are preferred. This approach simplifies clinical tracking of subsurface microstructural changes by eliminating the need for complex inverse problem solving, enabling rapid data acquisition and minimal processing.

Chemical Mapping of Nanoparticle–Ligand Interfaces in Optical Nanocavities

Mon, 30 Jun 2025 00:00:00 +0000

Understanding processes in photon-phonon scattering, absorption, and chemical reactions in optical nanocavities is important for single-molecule sensors, single-photon emitters, and photocatalysis. However, the influence of electromagnetic fields, charge transfer, and molecular geometry is challenging to probe by ensemble-averaged spectroscopic techniques over multiple nanocavities. Photoinduced force microscopy (PiFM), which measures photoinduced polarizability under infrared excitation of a sample in the nanocavity between the scanning probe microscopy tip and sample surface, is used here for simultaneous nanoscale topological and chemical characterization. First-principles density functional theory (DFT) simulations of the vibrational spectra of gold nanoparticle surfaces functionalized with benzenedithiol (Au-BDT) elucidate molecular orientation, charge transfer, and oxidation state for understanding molecular and adatom reconfiguration in optical nanocavities in response...

Structured light imaging mesoscopy: detection of embedded morphological changes in superficial tissues

Mon, 23 Jun 2025 00:00:00 +0000

Significance: Current paradigms for the optical characterization of layered tissues involve explicit consideration of an inverse problem which is often ill-posed and whose resolution may retain significant uncertainty. Here, we present an alternative approach, structured light imaging mesoscopy (SLIM), that leverages the inherent sensitivity of raw spatial frequency domain (SFD) reflectance measurements for the detection of embedded subsurface scattering changes in tissue. Aim: We identify wavelength-spatial frequency ( ) combinations that provide optimal sensitivity of SFD reflectance changes originating from scattering changes in an embedded tissue layer. We specifically consider the effects of scattering changes in the superficial dermis which is a key locus of pathology for diverse skin conditions such as cancer, aging, and scleroderma. Approach: We used Monte Carlo simulations in a four-layer skin model to analyze the SFD reflectance changes resulting from changes in superficial...

Proton-Transfer Kinetics at Liquid–Liquid Interfaces

Tue, 17 Jun 2025 00:00:00 +0000

Proton transfer at electrochemical interfaces is fundamentally important across science and technology, yet kinetic measurements of this elementary step at electrode|electrolyte interfaces are convoluted with other electron-transfer steps and by inhomogeneous electrode surfaces. We use facilitated proton transfer at the interface between two immiscible electrolyte solutions (ITIES) as a platform to study proton-transfer kinetics in the absence of interfacial electron transfer and without the defects at solid|electrolyte interfaces. Diffusion-controlled micropipette voltammetry revealed that 2,6-diphenylpyridine (DPP) facilitates proton transfer across the HCl(aq)|trifluorotoluene interface, while voltammetry at nanopipette-supported interfaces yielded activation-controlled ion-transfer currents. We extract kinetic parameters k_app⁰ and α_app, 3.0 ± 1.8 cm/s and 0.3 ± 0.2, respectively, for DPP-facilitated proton transfer by fitting quasi-reversible...

Transient Slope: A Metric for Assessing Heterogeneity from the Dielectrophoresis Spectrum

Fri, 9 May 2025 00:00:00 +0000

Cellular heterogeneity, an inherent feature of biological systems, plays a critical role in processes such as development, immune response, and disease progression. Human mesenchymal stem cells (hMSCs) exemplify this heterogeneity due to their multi-lineage differentiation potential. However, their inherent variability complicates clinical use, and there is no universally accepted method for detecting and quantifying cell population heterogeneity. Dielectrophoresis (DEP) has emerged as a powerful electrokinetic technique for characterizing and manipulating cells based on their dielectric properties, offering label-free analysis capabilities. Quantitative information from the DEP spectrum, such as transient slope, measure cells’ transition between negative and positive DEP behaviors. In this study, we employed DEP to estimate transient slope of various cell populations, including relatively homogeneous HEK-293 cells, heterogeneous hMSCs, and cancer cells (PC3 and DU145). Our analysis...

Electrical Phenotyping of Aged Human Mesenchymal Stem Cells Using Dielectrophoresis

Fri, 9 May 2025 00:00:00 +0000

Human mesenchymal stem cells (hMSCs) are widely used in regenerative medicine, but large-scale in vitro expansion alters their function, impacting proliferation and differentiation potential. Currently, a predictive marker to assess these changes is lacking. Here, we used dielectrophoresis (DEP) to characterize the electrical phenotype of hMSCs derived from bone marrow (BM), adipose tissue (AT), and umbilical cord (UC) as they aged in vitro from passage 4 (P4) to passage 9 (P9). The electrical phenotype was defined by the DEP spectra, membrane capacitance, and cytoplasm conductivity. Cell morphology and size, growth characteristics, adipogenic differentiation potential, and osteogenic differentiation potential were assessed alongside label-free biomarker membrane capacitance and cytoplasm conductivity. Differentiation was confirmed by histological staining and RT-qPCR. All hMSCs exhibited typical morphology, though cell size varied, with UC-hMSCs displaying the largest variability...

Phenotypic Characterization of 2D and 3D Prostate Cancer Cell Systems Using Electrical Impedance Spectroscopy

Fri, 9 May 2025 00:00:00 +0000

Prostate cancer is the second leading cause of death in men. A challenge in treating prostate cancer is overcoming cell plasticity, which links cell phenotype changes and chemoresistance. In this work, a microfluidic device coupled with electrical impedance spectroscopy (EIS), an electrode-based cell characterization technique, was used to study the electrical characteristics of phenotype changes for (1) prostate cancer cell lines (PC3, DU145, and LNCaP cells), (2) cells grown in 2D monolayer and 3D suspension cell culture conditions, and (3) cells in the presence (or absence) of the anti-cancer drug nigericin. To validate observations of phenotypic change, we measured the gene expression of two epithelial markers, E-cadherin (CDH1) and Tight Junction Protein 1 (ZO-1). Our results showed that PC3, DU145, and LNCaP cells were discernible with EIS. Secondly, moderate phenotype changes based on differences in cell culture conditions were detected with EIS and supported by the gene...

Electrical Impedance Spectroscopy as a Tool to Detect the Epithelial to Mesenchymal Transition in Prostate Cancer Cells

Fri, 9 May 2025 00:00:00 +0000

Prostate cancer (PCa) remains a significant health threat, with chemoresistance and recurrence posing major challenges despite advances in treatment. The epithelial to mesenchymal transition (EMT), a biochemical process where cells lose epithelial features and gain mesenchymal traits, is linked to chemoresistance and metastasis. Electrical impedance spectroscopy (EIS), a novel label-free electrokinetic technique, offers promise in detecting cell phenotype changes. In this study, we employed EIS to detect EMT in prostate cancer cells (PCCs). PC3, DU145, and LNCaP cells were treated with EMT induction media for five days. EIS characterization revealed unique impedance spectra correlating with metastatic potential, distinguishing DU145 EMT+ and EMT- cells, and LNCaP EMT+ and EMT- cells (in combination with dielectrophoresis), with comparisons made to epithelial and mesenchymal controls. These changes were supported by shifts in electrical signatures, morphologies, and protein expression,...

Divergent evolution of slip banding in CrCoNi alloys

Sat, 26 Apr 2025 00:00:00 +0000

Metallic materials under high stress often exhibit deformation localization, manifesting as slip banding. Over seven decades ago, Frank and Read introduced the well-known model of dislocation multiplication at a source, explaining slip band formation. Here, we reveal two distinct types of slip bands (confined and extended) in compressed CrCoNi alloys through multi-scale testing and modeling from microscopic to atomic scales. The confined slip band, characterized by a thin glide zone, arises from the conventional process of repetitive full dislocation emissions at Frank–Read source. Contrary to the classical model, the extended band stems from slip-induced deactivation of dislocation sources, followed by consequent generation of new sources on adjacent planes, leading to rapid band thickening. Our findings provide insights into atomic-scale collective dislocation motion and microscopic deformation instability in advanced structural materials.

Machine Learning‐Guided Discovery of Factors Governing Deformation Twinning in Mg–Y Alloys

Thu, 24 Apr 2025 00:00:00 +0000

Magnesium (Mg) alloys are promising lightweight structural materials whose limited strength and room-temperature ductility limit applications. Precise control of deformation-induced twinning through microstructural alloy design is being investigated to overcome these deficiencies. Motivated by the need to understand and control twin formation during deformation in Mg alloys, a series of magnesium-yttrium (Mg–Y) alloys are investigated using electron backscatter diffraction (EBSD). Analysis of EBSD maps produces a large dataset of microstructural information for >40000 grains. To quantitatively determine how processing parameters and microstructural features are correlated with twin formation, interpretable machine learning (ML) is employed to statistically analyze the individual effects of microstructural features on twinning. An ML classifier is trained to predict the likelihood of twin formation, given inputs including grain microstructural information and synthesis...

Ferroelectric tunnel junctions integrated on semiconductors with enhanced fatigue resistance

Thu, 24 Apr 2025 00:00:00 +0000

Oxide-based ferroelectric tunnel junctions (FTJs) show promise for nonvolatile memory and neuromorphic applications, making their integration with existing semiconductor technologies highly desirable. Furthermore, resistance fatigue in current silicon-based integration remains a critical issue. Understanding this fatigue mechanism in semiconductor-integrated FTJ is essential yet unresolved. Here, we systematically investigate the fatigue performance of ultrathin bismuth ferrite BiFeO₃ (BFO)-based FTJs integrated with various semiconductors. Notably, the BFO/gallium arsenide FTJ exhibits superior fatigue resistance characteristics (>10⁸ cycles), surpassing the BFO/silicon FTJ (>10⁶ cycles) and even approaching epitaxial oxide FTJs (>10⁹ cycles). The atomic-scale fatigue mechanism is revealed as lattice structure collapse caused by oxygen vacancy accumulation in BFO near semiconductors after repeated switching. The enhanced fatigue-resistant...

Durability of Pt‐Alloy Catalyst for Heavy‐Duty Polymer Electrolyte Fuel Cell Applications under Realistic Conditions

Thu, 10 Apr 2025 00:00:00 +0000

Abstract As an emerging technology, polymer electrolyte fuel cells (PEFCs) powered by clean hydrogen can be a great source of renewable power generation with flexible utilization because of high gravimetric energy density of hydrogen. To be used in real‐life applications, PEFCs need to maintain their performance for long‐term use under a wide range of conditions. Therefore, it's important to understand the degradation of the PEFC under protocols that are closely related to the catalyst lifetime. Alloying Pt with transitional metal improves catalyst activity. It is also crucial to understand Pt alloys degradation mechanisms to improve their durability. To study durability of Pt alloys, accelerated stress tests (ASTs) are performed on Pt−Co catalyst supported on two types of carbon. Two different AST protocols were being studied: Membrane Electrolyte Assembly (MEA) AST based on the protocol introduced by the Million Mile Fuel Cell Truck consortium in 2023 and Catalyst AST, adopted...

Hierarchical Assembly of Conductive Fibers from Coiled-Coil Peptide Building Blocks

Thu, 10 Apr 2025 00:00:00 +0000

Biology provides many sources of inspiration for synthetic and multifunctional nanomaterials. Naturally evolved proteins exhibit specialized, sequence-defined functions and self-assembly behavior. Recapitulating their molecularly defined self-assembly behavior, however, is challenging in de novo proteins. Peptides, on the other hand, represent a more well-defined and rationally designable space with the potential for sequence-programmable, stimuli-responsive design for structure and function, making them ideal building blocks of bioelectronic interfaces. In this work, we design peptides that exhibit stimuli-responsive self-assembly and the capacity to transport electrical current over micrometer-long distances. A lysine-lysine (KK) motif inserted at solvent-exposed positions of a coiled-coil-forming peptide sequence introduces pH-dependent control over a transition from unordered to α-helical peptide structure. The ordered state of the peptide serves as a building block...

Fluorescence Lifetime Imaging Detects Long-Lifetime Signal Associated with Reduced Pyocyanin at the Surface of Pseudomonas aeruginosa Biofilms and in Cross-Feeding Conditions

Mon, 7 Apr 2025 00:00:00 +0000

Understanding bacterial physiology in real-world environments requires noninvasive approaches and is a challenging yet necessary endeavor to effectively treat infectious disease. Bacteria evolve strategies to tolerate chemical gradients associated with infections. The DIVER (Deep Imaging Via Enhanced Recovery) microscope can image autofluorescence and fluorescence lifetime throughout samples with high optical scattering, enabling the study of naturally formed chemical gradients throughout intact biofilms. Using the DIVER, a long fluorescent lifetime signal associated with reduced pyocyanin, a molecule for electron cycling in low oxygen, was detected in low-oxygen conditions at the surface of Pseudomonas aeruginosa biofilms and in the presence of fermentation metabolites from Rothia mucilaginosa, which cocolonizes infected airways with P. aeruginosa. These findings underscore the utility of the DIVER microscope and fluorescent lifetime for noninvasive studies...

Fluorescence Lifetime Imaging Detects Long-Lifetime Signal Associated with Reduced Pyocyanin at the Surface of Pseudomonas aeruginosa Biofilms and in Cross-Feeding Conditions

Thu, 3 Apr 2025 00:00:00 +0000

From Static to Dynamic Structures: Improving Binding Affinity Prediction with Graph‐Based Deep Learning

Thu, 3 Apr 2025 00:00:00 +0000

Accurate prediction of protein-ligand binding affinities is an essential challenge in structure-based drug design. Despite recent advances in data-driven methods for affinity prediction, their accuracy is still limited, partially because they only take advantage of static crystal structures while the actual binding affinities are generally determined by the thermodynamic ensembles between proteins and ligands. One effective way to approximate such a thermodynamic ensemble is to use molecular dynamics (MD) simulation. Here, an MD dataset containing 3,218 different protein-ligand complexes is curated, and Dynaformer, a graph-based deep learning model is further developed to predict the binding affinities by learning the geometric characteristics of the protein-ligand interactions from the MD trajectories. In silico experiments demonstrated that the model exhibits state-of-the-art scoring and ranking power on the CASF-2016 benchmark dataset, outperforming the methods hitherto reported....

Improving molecular property prediction through a task similarity enhanced transfer learning strategy

Thu, 3 Apr 2025 00:00:00 +0000

Deeply understanding the properties (e.g., chemical or biological characteristics) of small molecules plays an essential role in drug development. A large number of molecular property datasets have been rapidly accumulated in recent years. However, most of these datasets contain only a limited amount of data, which hinders deep learning methods from making accurate predictions of the corresponding molecular properties. In this work, we propose a transfer learning strategy to alleviate such a data scarcity problem by exploiting the similarity between molecular property prediction tasks. We introduce an effective and interpretable computational framework, named MoTSE (Molecular Tasks Similarity Estimator), to provide an accurate estimation of task similarity. Comprehensive tests demonstrated that the task similarity derived from MoTSE can serve as useful guidance to improve the prediction performance of transfer learning on molecular properties. We also showed that MoTSE can capture...

Deciphering driver regulators of cell fate decisions from single-cell transcriptomics data with CEFCON

Thu, 3 Apr 2025 00:00:00 +0000

Single-cell technologies enable the dynamic analyses of cell fate mapping. However, capturing the gene regulatory relationships and identifying the driver factors that control cell fate decisions are still challenging. We present CEFCON, a network-based framework that first uses a graph neural network with attention mechanism to infer a cell-lineage-specific gene regulatory network (GRN) from single-cell RNA-sequencing data, and then models cell fate dynamics through network control theory to identify driver regulators and the associated gene modules, revealing their critical biological processes related to cell states. Extensive benchmarking tests consistently demonstrated the superiority of CEFCON in GRN construction, driver regulator identification, and gene module identification over baseline methods. When applied to the mouse hematopoietic stem cell differentiation data, CEFCON successfully identified driver regulators for three developmental lineages, which offered useful...

Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells

Thu, 3 Apr 2025 00:00:00 +0000

The generation of induced pluripotent stem cells (iPSC) from adult somatic cells is one of the most remarkable discoveries in recent decades. However, several works have reported evidence of genomic instability in iPSC, raising concerns on their biomedical use. The reasons behind the genomic instability observed in iPSC remain mostly unknown. Here we show that, similar to the phenomenon of oncogene-induced replication stress, the expression of reprogramming factors induces replication stress. Increasing the levels of the checkpoint kinase 1 (CHK1) reduces reprogramming-induced replication stress and increases the efficiency of iPSC generation. Similarly, nucleoside supplementation during reprogramming reduces the load of DNA damage and genomic rearrangements on iPSC. Our data reveal that lowering replication stress during reprogramming, genetically or chemically, provides a simple strategy to reduce genomic instability on mouse and human iPSC.

Primary Mammary Organoid Model of Lactation and Involution

Wed, 2 Apr 2025 00:00:00 +0000

Mammary gland development occurs mainly after birth and is composed of three successive stages: puberty, pregnancy and lactation, and involution. These developmental stages are associated with major tissue remodeling, including extensive changes in mammary epithelium, as well as surrounding stroma. Three-dimensional (3D) mammary organoid culture has become an important tool in mammary gland biology and enabled invaluable discoveries on pubertal mammary branching morphogenesis and breast cancer. However, a suitable 3D organoid model recapitulating key aspects of lactation and involution has been missing. Here, we describe a robust and straightforward mouse mammary organoid system modeling lactation and involution-like process, which can be applied to study mechanisms of physiological mammary gland lactation and involution as well as pregnancy-associated breast cancer.

A knowledge-guided pre-training framework for improving molecular representation learning

Wed, 2 Apr 2025 00:00:00 +0000

Learning effective molecular feature representation to facilitate molecular property prediction is of great significance for drug discovery. Recently, there has been a surge of interest in pre-training graph neural networks (GNNs) via self-supervised learning techniques to overcome the challenge of data scarcity in molecular property prediction. However, current self-supervised learning-based methods suffer from two main obstacles: the lack of a well-defined self-supervised learning strategy and the limited capacity of GNNs. Here, we propose Knowledge-guided Pre-training of Graph Transformer (KPGT), a self-supervised learning framework to alleviate the aforementioned issues and provide generalizable and robust molecular representations. The KPGT framework integrates a graph transformer specifically designed for molecular graphs and a knowledge-guided pre-training strategy, to fully capture both structural and semantic knowledge of molecules. Through extensive computational tests...

A Robust Mammary Organoid System to Model Lactation and Involution-like Processes.

Wed, 2 Apr 2025 00:00:00 +0000

The mammary gland is a highly dynamic tissue that changes throughout reproductive life, including growth during puberty and repetitive cycles of pregnancy and involution. Mammary gland tumors represent the most common cancer diagnosed in women worldwide. Studying the regulatory mechanisms of mammary gland development is essential for understanding how dysregulation can lead to breast cancer initiation and progression. Three-dimensional (3D) mammary organoids offer many exciting possibilities for the study of tissue development and breast cancer. In the present protocol derived from Sumbal et al., we describe a straightforward 3D organoid system for the study of lactation and involution ex vivo. We use primary and passaged mouse mammary organoids stimulated with fibroblast growth factor 2 (FGF2) and prolactin to model the three cycles of mouse mammary gland lactation and involution processes. This 3D organoid model represents a valuable tool to study late postnatal mammary...

Context-Dependent Impact of RAS Oncogene Expression on Cellular Reprogramming to Pluripotency

Wed, 2 Apr 2025 00:00:00 +0000

Induction of pluripotency in somatic cells with defined genetic factors has been successfully used to investigate the mechanisms of disease initiation and progression. Cellular reprogramming and oncogenic transformation share common features; both involve undergoing a dramatic change in cell identity, and immortalization is a key step for cancer progression that enhances reprogramming. However, there are very few examples of complete successful reprogramming of tumor cells. Here we address the effect of expressing an active oncogene, RAS, on the process of reprogramming and found that, while combined expression with reprogramming factors enhanced dedifferentiation, expression within the context of neoplastic transformation impaired reprogramming. RAS induces expression changes that promote loss of cell identity and acquisition of stemness in a paracrine manner and these changes result in reprogramming when combined with reprogramming factors. When cells carry cooperating oncogenic...

Protocol for quantitative evaluation of the impact of paracrine senescence on cellular reprogramming in cultured cells and mouse models

Wed, 2 Apr 2025 00:00:00 +0000

We present a protocol to evaluate the impact of senescence secretome on reprogramming to pluripotency using both cellular and mouse models. First, we describe the in vitro reprogramming procedure using conditioned medium derived from senescent cells. Next, to explore the impact of senescence on in vivo reprogramming, we detail the steps to identify senescent and reprogrammed cells in mouse skeletal muscle, followed by semi-automatic quantification. This protocol can be used to study the effect of paracrine senescence on cellular plasticity. For complete details on the use and execution of this protocol, please refer to von Joest et al. (2022).¹.

Performance Tuning of Polarizable Gaussian Multipole Model in Molecular Dynamics Simulations

Tue, 1 Apr 2025 00:00:00 +0000

Molecular dynamics (MD) simulations are essential for understanding molecular phenomena at the atomic level, with their accuracy largely dependent on both the employed force field and sampling. Polarizable force fields, which incorporate atomic polarization effects, represent a significant advancement in simulation technology. The polarizable Gaussian multipole (pGM) model has been noted for its accurate reproduction of ab initio electrostatic interactions. In this study, we document our effort to enhance the computational efficiency and scalability of the pGM simulations within the AMBER framework using MPI (message passing interface). Performance evaluations reveal that our MPI-based pGM model significantly reduces runtime and scales effectively while maintaining computational accuracy. Additionally, we investigated the stability and reliability of the MPI implementation under the NVE simulation ensemble. Optimal Ewald and induction parameters for the pGM model are also...

Modeling gene interactions in polygenic prediction via geometric deep learning

Tue, 1 Apr 2025 00:00:00 +0000

Polygenic risk score (PRS) is a widely used approach for predicting individuals' genetic risk of complex diseases, playing a pivotal role in advancing precision medicine. Traditional PRS methods, predominantly following a linear structure, often fall short in capturing the intricate relationships between genotype and phenotype. In this study, we present PRS-Net, an interpretable geometric deep learning-based framework that effectively models the nonlinearity of biological systems for enhanced disease prediction and biological discovery. PRS-Net begins by deconvoluting the genome-wide PRS at the single-gene resolution and then explicitly encapsulates gene-gene interactions leveraging a graph neural network (GNN) for genetic risk prediction, enabling a systematic characterization of molecular interplay underpinning diseases. An attentive readout module is introduced to facilitate model interpretation. Extensive tests across multiple complex traits and diseases demonstrate the superior...

Understanding Performance Limitation of Liquid Alkaline Water Electrolyzers

Tue, 25 Mar 2025 00:00:00 +0000

Liquid alkaline water electrolyzers (LAWEs), being the most commercially mature electrolysis technology, play a pivotal role in large-scale hydrogen production. However, LAWEs suffer from low operational efficiency, primarily due to un-optimized electrode structure and chemical compositions. Thus, we investigated how various electrode configurations could impact LAWE performance. Our results show that Ni felt electrodes outperform the conventional Ni foam thanks to improved electrochemical active surface area (ECSA) and preferred electrode surface structure that minimizes the micro-gaps in between the electrode and separator. By comparing the stainless steel (SS) felt electrodes with Ni felt electrodes, SS not only shows better oxygen evolution reaction activity but also improved hydrogen evolution reaction activity, which is less studied in the literature. We also show that a bilayer structure with small pore radius facing the separator could further improve LAWE performance...

Photoelectrochemical characterization of infrared-absorbing osmium-polypyridyl dyes bound to TiO2