Ligand-modified nanoparticle surfaces influence CO electroreduction selectivity.

Improving the kinetics and selectivity of CO2/CO electroreduction to valuable multi-carbon products is a challenge for science and is a requirement for practical relevance. Here we develop a thiol-modified surface ligand strategy that promotes electrochemical CO-to-acetate. We explore a picture wherein nucleophilic interaction between the lone pairs of sulfur and the empty orbitals of reaction intermediates contributes to making the acetate pathway more energetically accessible. Density functional theory calculations and Raman spectroscopy suggest a mechanism where the nucleophilic interaction increases the sp2 hybridization of CO(ad), facilitating the rate-determining step, CO* to (CHO)*. We find that the ligands stabilize the (HOOC-CH2)* intermediate, a key intermediate in the acetate pathway. In-situ Raman spectroscopy shows shifts in C-O, Cu-C, and C-S vibrational frequencies that agree with a picture of surface ligand-intermediate interactions. A Faradaic efficiency of 70% is obtained on optimized thiol-capped Cu catalysts, with onset potentials 100 mV lower than in the case of reference Cu catalysts.

CO2 Electrolyzers.

CO2 electrolyzers have progressed rapidly in energy efficiency and catalyst selectivity toward valuable chemical feedstocks and fuels, such as syngas, ethylene, ethanol, and methane. However, each component within these complex systems influences the overall performance, and the further advances needed to realize commercialization will require an approach that considers the whole process, with the electrochemical cell at the center. Beyond the cell boundaries, the electrolyzer must integrate with upstream CO2 feeds and downstream separation processes in a way that minimizes overall product energy intensity and presents viable use cases. Here we begin by describing upstream CO2 sources, their energy intensities, and impurities. We then focus on the cell, the most common CO2 electrolyzer system architectures, and each component within these systems. We evaluate the energy savings and the feasibility of alternative approaches including integration with CO2 capture, direct conversion of flue gas and two-step conversion via carbon monoxide. We evaluate pathways that minimize downstream separations and produce concentrated streams compatible with existing sectors. Applying this comprehensive upstream-to-downstream approach, we highlight the most promising routes, and outlook, for electrochemical CO2 reduction.

Selective Suppression of Integrin-Ligand Binding by Single Molecular Tension Probes Mediates Directional Cell Migration.

Cell migration interacting with continuously changing microenvironment, is one of the most essential cellular functions, participating in embryonic development, wound repair, immune response, and cancer metastasis. The migration process is finely tuned by integrin-mediated binding to ligand molecules. Although numerous biochemical pathways orchestrating cell adhesion and motility are identified, how subcellular forces between the cell and extracellular matrix regulate intracellular signaling for cell migration remains unclear. Here, it is showed that a molecular binding force across integrin subunits determines directional migration by regulating tension-dependent focal contact formation and focal adhesion kinase phosphorylation. Molecular binding strength between integrin αvß3 and fibronectin is precisely manipulated by developing molecular tension probes that control the mechanical tolerance applied to cell-substrate interfaces. This data reveals that integrin-mediated molecular binding force reduction suppresses cell spreading and focal adhesion formation, attenuating the focal adhesion kinase (FAK) phosphorylation that regulates the persistence of cell migration. These results further demonstrate that manipulating subcellular binding forces at the molecular level can recapitulate differential cell migration in response to changes of substrate rigidity that determines the physical condition of extracellular microenvironment. Novel insights is provided into the subcellular mechanics behind global mechanical adaptation of the cell to surrounding tissue environments featuring distinct biophysical signatures.

Stretching of porous poly (l-lactide-co-ε-caprolactone) membranes regulates the differentiation of mesenchymal stem cells.

Background: Among a variety of biomaterials supporting cell growth for therapeutic applications, poly (l-lactide-co-ε-caprolactone) (PLCL) has been considered as one of the most attractive scaffolds for tissue engineering owing to its superior mechanical strength, biocompatibility, and processibility. Although extensive studies have been conducted on the relationship between the microstructure of polymeric materials and their mechanical properties, the use of the fine-tuned morphology and mechanical strength of PLCL membranes in stem cell differentiation has not yet been studied. Methods: PLCL membranes were crystallized in a combination of diverse solvent-nonsolvent mixtures, including methanol (MeOH), isopropanol (IPA), chloroform (CF), and distilled water (DW), with different solvent polarities. A PLCL membrane with high mechanical strength induced by limited pore formation was placed in a custom bioreactor mimicking the reproducible physiological microenvironment of the vascular system to promote the differentiation of mesenchymal stem cells (MSCs) into smooth muscle cells (SMCs). Results: We developed a simple, cost-effective method for fabricating porosity-controlled PLCL membranes based on the crystallization of copolymer chains in a combination of solvents and non-solvents. We confirmed that an increase in the ratio of the non-solvent increased the chain aggregation of PLCL by slow evaporation, leading to improved mechanical properties of the PLCL membrane. Furthermore, we demonstrated that the cyclic stretching of PLCL membranes induced MSC differentiation into SMCs within 10 days of culture. Conclusion: The combination of solvent and non-solvent casting for PLCL solidification can be used to fabricate mechanically durable polymer membranes for use as mechanosensitive scaffolds for stem cell differentiation.

Serine synthesis pathway upregulated by E-cadherin is essential for the proliferation and metastasis of breast cancers.

The loss of E-cadherin (E-cad), an epithelial cell adhesion molecule, has been implicated in the epithelial-mesenchymal transition (EMT), promoting invasion and migration of cancer cells and, consequently, metastasis. However, recent studies have demonstrated that E-cad supports the survival and proliferation of metastatic cancer cells, suggesting that our understanding of E-cad in metastasis is far from comprehensive. Here, we report that E-cad upregulates the de novo serine synthesis pathway (SSP) in breast cancer cells. The SSP provides metabolic precursors for biosynthesis and resistance to oxidative stress, critically beneficial for E-cad-positive breast cancer cells to achieve faster tumor growth and more metastases. Inhibition of PHGDH, a rate-limiting enzyme in the SSP, significantly and specifically hampered the proliferation of E-cad-positive breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. Our findings reveal that E-cad adhesion molecule significantly reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers.

Smart contact lens systems for ocular drug delivery and therapy.

Ocular drug delivery and therapy systems have been extensively investigated with various methods including direct injections, eye drops and contact lenses. Nowadays, smart contact lens systems are attracting a lot of attention for ocular drug delivery and therapy due to their minimally invasive or non-invasive characteristics, highly enhanced drug permeation, high bioavailability, and on-demand drug delivery. Furthermore, smart contact lens systems can be used for direct light delivery into the eyes for biophotonic therapy replacing the use of drugs. Here, we review smart contact lens systems which can be classified into two groups of drug-eluting contact lens and ocular device contact lens. More specifically, this review covers smart contact lens systems with nanocomposite-laden systems, polymeric film-incorporated systems, micro and nanostructure systems, iontophoretic systems, electrochemical systems, and phototherapy systems for ocular drug delivery and therapy. After that, we discuss the future opportunities, challenges and perspectives of smart contact lens systems for ocular drug delivery and therapy.

Spatio-temporal coupling of RMS errors in laser amplification.

We developed a theoretical model for the relationship between the input and amplified laser beams of energy stability and spatial uniformity in the amplification process. 10 Hz, 8 ns, 1064 nm Nd:YAG Q-switched resonator with Nd:YAG main amplifier was employed for the experiment. The theoretical model simulation and Frantz-Nodvik simulation were performed by utilizing the obtained beam image, acquired energy from the experiment, and stored fluence from the gain medium. The result indicated that the fluctuation of the spatial distribution in a single beam influences the stability of temporally distributed energy during the amplification process of the laser beam, thereby improving energy stability.

Bipolar membrane electrolyzers enable high single-pass CO2 electroreduction to multicarbon products.

In alkaline and neutral MEA CO2 electrolyzers, CO2 rapidly converts to (bi)carbonate, imposing a significant energy penalty arising from separating CO2 from the anode gas outlets. Here we report a CO2 electrolyzer uses a bipolar membrane (BPM) to convert (bi)carbonate back to CO2, preventing crossover; and that surpasses the single-pass utilization (SPU) limit (25% for multi-carbon products, C2+) suffered by previous neutral-media electrolyzers. We employ a stationary unbuffered catholyte layer between BPM and cathode to promote C2+ products while ensuring that (bi)carbonate is converted back, in situ, to CO2 near the cathode. We develop a model that enables the design of the catholyte layer, finding that limiting the diffusion path length of reverted CO2 to ~10 µm balances the CO2 diffusion flux with the regeneration rate. We report a single-pass CO2 utilization of 78%, which lowers the energy associated with downstream separation of CO2 by 10× compared with past systems.

A metal-supported single-atom catalytic site enables carbon dioxide hydrogenation.

Nitrogen-doped graphene-supported single atoms convert CO2 to CO, but fail to provide further hydrogenation to methane - a finding attributable to the weak adsorption of CO intermediates. To regulate the adsorption energy, here we investigate the metal-supported single atoms to enable CO2 hydrogenation. We find a copper-supported iron-single-atom catalyst producing a high-rate methane. Density functional theory calculations and in-situ Raman spectroscopy show that the iron atoms attract surrounding intermediates and carry out hydrogenation to generate methane. The catalyst is realized by assembling iron phthalocyanine on the copper surface, followed by in-situ formation of single iron atoms during electrocatalysis, identified using operando X-ray absorption spectroscopy. The copper-supported iron-single-atom catalyst exhibits a CO2-to-methane Faradaic efficiency of 64% and a partial current density of 128 mA cm-2, while the nitrogen-doped graphene-supported one produces only CO. The activity is 32 times higher than a pristine copper under the same conditions of electrolyte and bias.

Bimetallic Nanocatalysts Immobilized in Nanoporous Hydrogels for Long-Term Robust Continuous Glucose Monitoring of Smart Contact Lens.

Smart contact lenses for continuous glucose monitoring (CGM) have great potential for huge clinical impact. To date, their development has been limited by challenges in accurate detection of glucose without hysteresis for tear glucose monitoring to track the blood glucose levels. Here, long-term robust CGM in diabetic rabbits is demonstrated by using bimetallic nanocatalysts immobilized in nanoporous hydrogels in smart contact lenses. After redox reaction of glucose oxidase, the nanocatalysts facilitate rapid decomposition of hydrogen peroxide and nanoparticle-mediated charge transfer with drastically improved diffusion via rapid swelling of nanoporous hydrogels. The ocular glucose sensors result in high sensitivity, fast response time, low detection limit, low hysteresis, and rapid sensor warming-up time. In diabetic rabbits, smart contact lens can detect tear glucose levels consistent with blood glucose levels measured by a glucometer and a CGM device, reflecting rapid concentration changes without hysteresis. The CGM in a human demonstrates the feasibility of smart contact lenses for further clinical applications.

Smart Wireless Near-Infrared Light Emitting Contact Lens for the Treatment of Diabetic Retinopathy.

Diabetic retinopathy is currently treated by highly invasive repeated therapeutic injections and surgical interventions without complete vision recovery. Here, a noninvasive smart wireless far red/near-infrared (NIR) light emitting contact lens developed successfully for the repeated treatment of diabetic retinopathy with significantly improved compliance. A far red/NIR light emitting diode (LED) is connected with an application-specific integrated circuit chip, wireless power, and communication systems on a PET film, which is embedded in a silicone elastomer contact lens by thermal crosslinking. After in vitro characterization, it is confirmed that the retinal vascular hyper-permeability induced by diabetic retinopathy in rabbits is reduced to a statistically significant level by simply repeated wearing of smart far red/NIR LED contact lens for 8 weeks with 120 µW light irradiation for 15 min thrice a week. Histological analysis exhibits the safety and feasibility of LED contact lenses for treating diabetic retinopathy. This platform technology for smart LED contact lens would be harnessed for various biomedical photonic applications.

Supramolecular host-guest hyaluronic acid hydrogels enhance corneal wound healing through dynamic spatiotemporal effects.

Severe corneal wounds can lead to ulceration and scarring if not promptly and adequately treated. Hyaluronic acid (HA) has been investigated for the treatment of corneal wounds due to its remarkable biocompatibility, transparency and mucoadhesive properties. However, linear HA has low retention time on the cornea while many chemical moieties used to crosslink HA can cause toxicity, which limits their clinical ocular applications. Here, we used supramolecular non-covalent host-guest interactions between HA-cyclodextrin and HA-adamantane to form shear-thinning HA hydrogels and evaluated their impact on corneal wound healing. Supramolecular HA hydrogels facilitated adhesion and spreading of encapsulated human corneal epithelial cells ex vivo and improved corneal wound healing in vivo as an in situ-formed, acellular therapeutic membrane. The HA hydrogels were absorbed within the corneal stroma over time, modulated mesenchymal cornea stromal cell secretome production, reduced cellularity and inflammation of the anterior stroma, and significantly mitigated corneal edema compared to treatment with linear HA and untreated control eyes. Taken together, our results demonstrate supramolecular HA hydrogels as a promising and versatile biomaterial platform for corneal wound healing.

Micro-Slab Coil Design for Hyperpolarized Metabolic Flux Analysis in Multiple Samples.

Abnormal metabolism is a hallmark of cancer cells. Accumulating evidence suggests that metabolic changes are likely to occur before other cellular responses in cancer cells upon drug treatment. Therefore, the metabolic activity or flux in cancer cells could be a potent biomarker for cancer detection and treatment monitoring. Magnetic resonance (MR)-based sensing technologies have been developed with hyperpolarized molecules for real-time flux analysis, but they still suffer from low sensitivity and throughput. To address this limitation, we have developed an innovative miniaturized MR coil, termed micro-slab MR coil, for simultaneous analysis of metabolic flux in multiple samples. Combining this approach with hyperpolarized probes, we were able to quantify the pyruvate-to-lactate flux in two different leukemic cell lines in a non-destructive manner, simultaneously. Further, we were able to rapidly assess flux changes with drug treatment in a single hyperpolarization experiment. This new multi-sample system has the potential to transform our ability to assess metabolic dynamics at scale.

Ternary Alloys Enable Efficient Production of Methoxylated Chemicals via Selective Electrocatalytic Hydrogenation of Lignin Monomers.

We explore the selective electrocatalytic hydrogenation of lignin monomers to methoxylated chemicals, of particular interest, when powered by renewable electricity. Prior studies, while advancing the field rapidly, have so far lacked the needed selectivity: when hydrogenating lignin-derived methoxylated monomers to methoxylated cyclohexanes, the desired methoxy group (-OCH3) has also been reduced. The ternary PtRhAu electrocatalysts developed herein selectively hydrogenate lignin monomers to methoxylated cyclohexanes-molecules with uses in pharmaceutics. Using X-ray absorption spectroscopy and in situ Raman spectroscopy, we find that Rh and Au modulate the electronic structure of Pt and that this modulating steers intermediate energetics on the electrocatalyst surface to facilitate the hydrogenation of lignin monomers and suppress C-OCH3 bond cleavage. As a result, PtRhAu electrocatalysts achieve a record 58% faradaic efficiency (FE) toward 2-methoxycyclohexanol from the lignin monomer guaiacol at 200 mA cm-2, representing a 1.9× advance in FE and a 4× increase in partial current density compared to the highest productivity prior reports. We demonstrate an integrated lignin biorefinery where wood-derived lignin monomers are selectively hydrogenated and funneled to methoxylated 2-methoxy-4-propylcyclohexanol using PtRhAu electrocatalysts. This work offers an opportunity for the sustainable electrocatalytic synthesis of methoxylated pharmaceuticals from renewable biomass.

3D-Printable Fluoropolymer Gas Diffusion Layers for CO2 Electroreduction.

The electrosynthesis of value-added multicarbon products from CO2 is a promising strategy to shift chemical production away from fossil fuels. Particularly important is the rational design of gas diffusion electrode (GDE) assemblies to react selectively, at scale, and at high rates. However, the understanding of the gas diffusion layer (GDL) in these assemblies is limited for the CO2 reduction reaction (CO2 RR): particularly important, but incompletely understood, is how the GDL modulates product distributions of catalysts operating in high current density regimes > 300 mA cm-2 . Here, 3D-printable fluoropolymer GDLs with tunable microporosity and structure are reported and probe the effects of permeance, microstructural porosity, macrostructure, and surface morphology. Under a given choice of applied electrochemical potential and electrolyte, a 100× increase in the C2 H4 :CO ratio due to GDL surface morphology design over a homogeneously porous equivalent and a 1.8× increase in the C2 H4 partial current density due to a pyramidal macrostructure are observed. These findings offer routes to improve CO2 RR GDEs as a platform for 3D catalyst design.

Cell-ECM contact-guided intracellular polarization is mediated via lamin A/C dependent nucleus-cytoskeletal connection.

Cell polarization plays a crucial role in dynamic cellular events, such as cell proliferation, differentiation, and directional migration in response to diverse extracellular and intracellular signals. Although it is well known that cell polarization entails highly orchestrated intracellular molecular reorganization, the underlying mechanism of repositioning by intracellular organelles in the presence of multiple stimuli is still unclear. Here, we show that front-rear cell polarization based on the relative positions of nucleus and microtubule organizing center is precisely controlled by mechanical interactions including cellular adhesion to extracellular matrix and nucleus-cytoskeletal connections. By modulating the size and distribution of fibronectin-coated adhesive spots located in the polarized cell shape mimicking micropatterns, we monitored the alterations in cell polarity. We found that the localization of individual adhesive spots is more dominant than the cell shape itself to induce intracellular polarization. Further, the degree of cell polarization was diminished significantly by disrupting nuclear lamin A/C. We further confirm that geometrical cue-guided intracellular polarization determines directional cell migration via local activation of Cdc42. These findings provide novel insights into the role of nucleus-cytoskeletal connections in single cell polarization under a combination of physical, molecular, and genetic cues, where lamin A/C acts as a critical molecular mediator in ECM sensing and signal transduction via nucleus-cytoskeletal connection.

Intermediate Binding Control Using Metal-Organic Frameworks Enhances Electrochemical CO2 Reduction.

In the electrochemical CO2 reduction reaction (CO2RR), control over the binding of intermediates is key for tuning product selectivity and catalytic activity. Here we report the use of reticular chemistry to control the binding of CO2RR intermediates on metal catalysts encapsulated inside metal-organic frameworks (MOFs), thereby allowing us to improve CO2RR electrocatalysis. By varying systematically both the organic linker and the metal node in a face-centered cubic (fcu) MOF, we tune the adsorption of CO2, pore openness, and Lewis acidity of the MOFs. Using operando X-ray absorption spectroscopy (XAS) and in situ Raman spectroscopy, we reveal that the MOFs are stable under operating conditions and that this tuning plays the role of optimizing the *CO binding mode on the surface of Ag nanoparticles incorporated inside the MOFs with the increase of local CO2 concentration. As a result, we improve the CO selectivity from 74% for Ag/Zr-fcu-MOF-1,4-benzenedicarboxylic acid (BDC) to 94% for Ag/Zr-fcu-MOF-1,4-naphthalenedicarboxylic acid (NDC). The work offers a further avenue to utilize MOFs in the pursuit of materials design for CO2RR.

Analysis of Visuo Motor Control between Dominant Hand and Non-Dominant Hand for Effective Human-Robot Collaboration.

The human-in-the-loop technology requires studies on sensory-motor characteristics of each hand for an effective human-robot collaboration. This study aims to investigate the differences in visuomotor control between the dominant (DH) and non-dominant hands in tracking a target in the three-dimensional space. We compared the circular tracking performances of the hands on the frontal plane of the virtual reality space in terms of radial position error (ΔR), phase error (Δθ), acceleration error (Δa), and dimensionless squared jerk (DSJ) at four different speeds for 30 subjects. ΔR and Δθ significantly differed at relatively high speeds (ΔR: 0.5 Hz; Δθ: 0.5, 0.75 Hz), with maximum values of ≤1% compared to the target trajectory radius. DSJ significantly differed only at low speeds (0.125, 0.25 Hz), whereas Δa significantly differed at all speeds. In summary, the feedback-control mechanism of the DH has a wider range of speed control capability and is efficient according to an energy saving model. The central nervous system (CNS) uses different models for the two hands, which react dissimilarly. Despite the precise control of the DH, both hands exhibited dependences on limb kinematic properties at high speeds (0.75 Hz). Thus, the CNS uses a different strategy according to the model for optimal results.

Analysis of motor control strategy for frontal and sagittal planes of circular tracking movements using visual feedback noise from velocity change and depth information.

We aim to investigate a control strategy for the circular tracking movement in a three-dimensional (3D) space based on the accuracy of the visual information. After setting the circular orbits for the frontal and sagittal planes in the 3D virtual space, the subjects track a target moving at a constant velocity. The analysis is applied to two parameters of the polar coordinates, namely, ΔR (the difference in the distance from the center of a circular orbit) and Δω (the difference in the angular velocity). The movement in the sagittal plane provides different depth information depending on the position of the target in orbit, unlike the task of the frontal plane. Therefore, the circular orbit is divided into four quadrants for a statistical analysis of ΔR. In the sagittal plane, the error was two to three times larger in quadrants 1 and 4 than in quadrants 2 and 3 close to the subject. Here, Δω is estimated using a frequency analysis; the lower the accuracy of the visual information, the greater the periodicity. When comparing two different planes, the periodicity in the sagittal plane was approximately 1.7 to 2 times larger than that of the frontal plane. In addition, the average angular velocity of the target and tracer was within 0.6% during a single cycle. We found that if the amount of visual information is reduced, an optimal feedback control strategy can be used to reduce the positional error within a specific area.

Mechanical Properties of Materials for Stem Cell Differentiation.

Recent findings about cell fate change induced by physical stimuli have expedited the discovery of underlying regulatory mechanisms that determine stem cell differentiation. Progress with regards to micro-/nanofabrication technology have led to the development of advanced materials that can mimic biophysical features of in vivo related circumstances of the human body. Since the cellular microenvironment directly defines cellular structure and function, diverse material properties including stiffness, topology, and surface chemistry are investigated to regulate multiple signaling cascades involved in stem cell differentiation for the development of innovative tools that can be widely utilized in various fields ranging from basic research to medical applications. This progress report addresses essential biophysical regulation and alteration of material properties applied to control stem cell differentiation. It also presents novel strategies to regulate stem cell differentiation based on relationships between recently discovered mechanotransduction pathways and cell differentiation signaling. A new perspective on stem cell physiology will further provide a framework of biomedical applications such as regenerative medicine and stem cell therapy.