Quantitative Real-Time Analysis of Living Materials by Stimulated Raman Scattering Microscopy.

Composite materials built in part from living organisms have the potential to exhibit useful autonomous, adaptive, and self-healing behavior. The physicochemical, biological, and mechanical properties of such materials can be engineered through the genetic manipulation of their living components. Successful development of living materials will require not only new methods for design and preparation but also new analytical tools that are capable of real-time noninvasive mapping of chemical compositions. Here, we establish a strategy based on stimulated Raman scattering microscopy to monitor phosphatase-catalyzed mineralization of engineered bacterial films in situ. Real-time label-free imaging elucidates the mineralization process, quantifies both the organic and inorganic components of the material as functions of time, and reveals spatial heterogeneity at multiple scales. In addition, we correlate the mechanical performance of films with the extent of mineralization. This work introduces a promising strategy for quantitatively analyzing living materials, which should contribute to the accelerated development of such materials in the future.

The Potential Regulation of Working Anode for Long-Term Zero-Volt Storage at 37 °C in Li-Ion Batteries.

The advanced lithium-ion batteries that can tolerate zero-volt storage (ZVS) are in high demand for implantable medical devices and spacecraft. However, ZVS can raise the anode potential, leading to Cu current collector dissolution and solid-electrolyte interphase (SEI) degradation, especially at 37 °C. In this contribution, by quantitatively regulating the dosage of Li6CoO4 cathode additives, controllable potential of the working anode under abusive-discharge conditions is demonstrated. The addition of Li6CoO4 keeps zero-crossing potential (ZCP) and the potential of ZVS below 2.0 V (vs Li/Li+) for LiCoO2|mesocarbon microbead cells at 37 °C. The capacity retention ratio (CRR) increases from 69.1% and 35.9% to 98.6% and 90.8% after 10 and 20 days of ZVS, respectively. The Cu dissolution and SEI degradation are effectively suppressed, while the over-lithiated cathode exhibits high reversible capacity after ZVS. The limiting conditions of long-term ZVS are further explored and a corresponding guide map is designed. When quantitatively regulating ZCP and the potential in ZVS, Cu dissolution, SEI degradation, and irreversible conversion of the cathode constitute the limiting conditions. This contribution designs the most reasonable potential range for ZVS protection at 37 °C, and realizes the best CRR record through precise potential regulation for the first time.

Truly Tiny Acoustic Biomolecules for Ultrasound Imaging and Therapy.

Nanotechnology offers significant advantages for medical imaging and therapy, including enhanced contrast and precision targeting. However, integrating these benefits into ultrasonography is challenging due to the size and stability constraints of conventional bubble-based agents. Here bicones, truly tiny acoustic contrast agents based on gas vesicles (GVs), a unique class of air-filled protein nanostructures naturally produced in buoyant microbes, are described. It is shown that these sub-80 nm particles can be effectively detected both in vitro and in vivo, infiltrate tumors via leaky vasculature, deliver potent mechanical effects through ultrasound-induced inertial cavitation, and are easily engineered for molecular targeting, prolonged circulation time, and payload conjugation.

Functional nanoporous graphene superlattice.

Two-dimensional (2D) superlattices, formed by stacking sublattices of 2D materials, have emerged as a powerful platform for tailoring and enhancing material properties beyond their intrinsic characteristics. However, conventional synthesis methods are limited to pristine 2D material sublattices, posing a significant practical challenge when it comes to stacking chemically modified sublattices. Here we report a chemical synthesis method that overcomes this challenge by creating a unique 2D graphene superlattice, stacking graphene sublattices with monodisperse, nanometer-sized, square-shaped pores and strategically doped elements at the pore edges. The resulting graphene superlattice exhibits remarkable correlations between quantum phases at both the electron and phonon levels, leading to diverse functionalities, such as electromagnetic shielding, energy harvesting, optoelectronics, and thermoelectrics. Overall, our findings not only provide chemical design principles for synthesizing and understanding functional 2D superlattices but also expand their enhanced functionality and extensive application potential compared to their pristine counterparts.

Using ultrasound to 3D-print materials.

Ultrasound allows additive manufacturing to go deeper-potentially inside the body.

Ultrasonic reporters of calcium for deep tissue imaging of cellular signals.

Calcium imaging has enabled major biological discoveries. However, the scattering of light by tissue limits the use of standard fluorescent calcium indicators in living animals. To address this limitation, we introduce the first genetically encoded ultrasonic reporter of calcium (URoC). Based on a unique class of air-filled protein nanostructures called gas vesicles, we engineered URoC to produce elevated nonlinear ultrasound signal upon binding to calcium ions. With URoC expressed in mammalian cells, we demonstrate noninvasive ultrasound imaging of calcium signaling in vivo during drug-induced receptor activation. URoC brings the depth and resolution advantages of ultrasound to the in vivo imaging of dynamic cellular function and paves the way for acoustic biosensing of a broader variety of biological signals.

In Situ Li-Plating Diagnosis for Fast-Charging Li-Ion Batteries Enabled by Relaxation-Time Detection.

The Li-plating behavior of Li-ion batteries under fast-charging conditions is elusive due to a lack of reliable indicators of the Li-plating onset. In this work, the relaxation time constant of the charge-transfer process (τCT ) is proposed to be promising for the determination of Li-plating onset. A novel pulse/relaxation test method enables rapid access to the τCT of the graphite anode during battery operation, applicable to both half and full batteries. The diagnosis of Li plating at varying temperatures and charging rates enriches the cognition of Li-plating behaviors. Li plating at low temperatures and high charging rates can be avoided because of the battery voltage limitations. Nevertheless, after the onset, severe Li plating evolves rapidly under harsh charging conditions, while the Li-plating process under benign charging conditions is accompanied by a simultaneous Li-intercalation process. The quantitative estimates indicate that Li plating at high temperatures/high charging rates leads to more irreversible capacity losses. This facile method with rational scientific principles can provide inspiration for exploring the safe boundaries of Li-ion batteries.

Remote control of mechanochemical reactions under physiological conditions using biocompatible focused ultrasound.

External control of chemical reactions in biological settings with spatial and temporal precision is a grand challenge for noninvasive diagnostic and therapeutic applications. While light is a conventional stimulus for remote chemical activation, its penetration is severely attenuated in tissues, which limits biological applicability. On the other hand, ultrasound is a biocompatible remote energy source that is highly penetrant and offers a wide range of functional tunability. Coupling ultrasound to the activation of specific chemical reactions under physiological conditions, however, remains a challenge. Here, we describe a synergistic platform that couples the selective mechanochemical activation of mechanophore-functionalized polymers with biocompatible focused ultrasound (FUS) by leveraging pressure-sensitive gas vesicles (GVs) as acousto-mechanical transducers. The power of this approach is illustrated through the mechanically triggered release of covalently bound fluorogenic and therapeutic cargo molecules from polymers containing a masked 2-furylcarbinol mechanophore. Molecular release occurs selectively in the presence of GVs upon exposure to FUS under physiological conditions. These results showcase the viability of this system for enabling remote control of specific mechanochemical reactions with spatiotemporal precision in biologically relevant settings and demonstrate the translational potential of polymer mechanochemistry.

Truly tiny acoustic biomolecules for ultrasound imaging and therapy.

Nanotechnology offers significant advantages for medical imaging and therapy, including enhanced contrast and precision targeting. However, integrating these benefits into ultrasonography has been challenging due to the size and stability constraints of conventional bubble-based agents. Here we describe bicones, truly tiny acoustic contrast agents based on gas vesicles, a unique class of air-filled protein nanostructures naturally produced in buoyant microbes. We show that these sub-80 nm particles can be effectively detected both in vitro and in vivo, infiltrate tumors via leaky vasculature, deliver potent mechanical effects through ultrasound-induced inertial cavitation, and are easily engineered for molecular targeting, prolonged circulation time, and payload conjugation.

Single-molecule visualization determines conformational substate ensembles in ß-sheet-rich peptide fibrils.

An understanding of protein conformational ensembles is essential for revealing the underlying mechanisms of interpeptide recognition and association. However, experimentally resolving multiple simultaneously existing conformational substates remains challenging. Here, we report the use of scanning tunneling microscopy (STM) to analyze the conformational substate ensembles of ß sheet peptides with a submolecular resolution (in-plane <2.6 Å). We observed ensembles of more than 10 conformational substates (with free energy fluctuations between several kBTs) in peptide homoassemblies of keratin (KRT) and amyloidal peptides (-5Aß42 and TDP-43 341-357). Furthermore, STM reveals a change in the conformational ensemble of peptide mutants, which is correlated with the macroscopic properties of peptide assemblies. Our results demonstrate that the STM-based single-molecule imaging can capture a thorough picture of the conformational substates with which to build an energetic landscape of interconformational interactions and can rapidly screen conformational ensembles, which can complement conventional characterization techniques.

Experimental Insights into Conformational Ensembles of Assembled ß-Sheet Peptides.

Deciphering the conformations and interactions of peptides in their assemblies offers a basis for guiding the rational design of peptide-assembled materials. Here we report the use of scanning tunneling microscopy (STM), a single-molecule imaging method with a submolecular resolution, to distinguish 18 types of coexisting conformational substates of the ß-strand of the 8-37 segment of human islet amyloid polypeptide (hIAPP 8-37). We analyzed the pairwise peptide-peptide interactions in the hIAPP 8-37 assembly and found 82 interconformation interactions within a free energy difference of 3.40 kBT. Besides hIAPP 8-37, this STM method validates the existence of multiple conformations of other ß-sheet peptide assemblies, including mutated hIAPP 8-37 and amyloid-ß 42. Overall, the results reported in this work provide single-molecule experimental insights into the conformational ensemble and interpeptide interactions in the ß-sheet peptide assembly.

Lubricated Interfaces Enabling Simultaneous Pulsatile and Continuous Chemical Release Modes.

The release of chemicals following either pulsatile or continuous release modes is important for various potential applications, including programmed chemical reactions, mechanical actuation, and treatments of various diseases. However, the simultaneous application of both modes in a single material system has been challenging. Here, two chemical loading methods are reported in a liquid-crystal-infused porous surface (LCIPS) that enables both a pulsatile and continuous release of chemicals simultaneously. Specifically, chemicals loaded in the porous substrate exhibit a liquid crystal (LC) mesophase-dependent continuous release, whereas the chemicals dissolved in micrometer-sized aqueous droplets dispersed in the LC surface follow a pulsatile release activated by a phase transition. Moreover, the loading method of distinct molecules can be controlled to program their release mode. Finally, the pulsatile and continuous release of two distinct bioactive small molecules, tetracycline and dexamethasone, are demonstrated which display antibacterial and immunomodulatory activities for applications such as chronic wound healing and biomedical implant coating.

40 Years of Low-Temperature Electrolytes for Rechargeable Lithium Batteries.

Rechargeable lithium batteries are one of the most appropriate energy storage systems in our electrified society, as virtually all portable electronic devices and electric vehicles today rely on the chemical energy stored in them. However, sub-zero Celsius operation, especially below -20 °C, remains a huge challenge for lithium batteries and greatly limits their application in extreme environments. Slow Li+ diffusion and charge transfer kinetics have been identified as two main origins of the poor performance of RLBs under low-temperature conditions, both strongly associated with the liquid electrolyte that governs bulk and interfacial ion transport. In this review, we first analyze the low-temperature kinetic behavior and failure mechanism of lithium batteries from an electrolyte standpoint. We next trace the history of low-temperature electrolytes in the past 40 years (1983-2022), followed by a comprehensive summary of the research progress as well as introducing the state-of-the-art characterization and computational methods for revealing their underlying mechanisms. Finally, we provide some perspectives on future research of low-temperature electrolytes with particular emphasis on mechanism analysis and practical application.

Staggered circular nanoporous graphene converts electromagnetic waves into electricity.

Harvesting largely ignored and wasted electromagnetic (EM) energy released by electronic devices and converting it into direct current (DC) electricity is an attractive strategy not only to reduce EM pollution but also address the ever-increasing energy crisis. Here we report the synthesis of nanoparticle-templated graphene with monodisperse and staggered circular nanopores enabling an EM-heat-DC conversion pathway. We experimentally and theoretically demonstrate that this staggered nanoporous structure alters graphene's electronic and phononic properties by synergistically manipulating its intralayer nanostructures and interlayer interactions. The staggered circular nanoporous graphene exhibits an anomalous combination of properties, which lead to an efficient absorption and conversion of EM waves into heat and in turn an output of DC electricity through the thermoelectric effect. Overall, our results advance the fundamental understanding of the structure-property relationships of ordered nanoporous graphene, providing an effective strategy to reduce EM pollution and generate electric energy.

CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemo-immunotherapy.

Glioblastoma (GBM) is one of the most aggressive and lethal solid tumors in human. While efficacious therapeutics, such as emerging chimeric antigen receptor (CAR)-T cells and chemotherapeutics, have been developed to treat various cancers, their effectiveness in GBM treatment has been hindered largely by the blood-brain barrier and blood-brain-tumor barriers. Human neutrophils effectively cross physiological barriers and display effector immunity against pathogens but the short lifespan and resistance to genome editing of primary neutrophils have limited their broad application in immunotherapy. Here we genetically engineer human pluripotent stem cells with CRISPR/Cas9-mediated gene knock-in to express various anti-GBM CAR constructs with T-specific CD3ζ or neutrophil-specific γ-signaling domains. CAR-neutrophils with the best anti-tumor activity are produced to specifically and noninvasively deliver and release tumor microenvironment-responsive nanodrugs to target GBM without the need to induce additional inflammation at the tumor sites. This combinatory chemo-immunotherapy exhibits superior and specific anti-GBM activities, reduces off-target drug delivery and prolongs lifespan in female tumor-bearing mice. Together, this biomimetic CAR-neutrophil drug delivery system is a safe, potent and versatile platform for treating GBM and possibly other devastating diseases.

Nucleation and Growth Mode of Solid Electrolyte Interphase in Li-Ion Batteries.

The solid electrolyte interphase (SEI) is regarded as the most important yet least understood component in Li-ion batteries. Considerable effort has been devoted to unravelling its chemistry, structure, and ion-transport mechanism; however, the nucleation and growth mode of SEI, which underlies all these properties, remains the missing piece. We quantify the growth mode of two representative SEIs on carbonaceous anodes based on classical nucleation theories and in situ atomic force microscopy imaging. The formation of inorganic SEI obeys the mixed 2D/3D growth model and is highly dependent on overpotential, whereby large overpotential favors 2D growth. Organic SEI strictly follows the 2D instantaneous nucleation and growth model regardless of overpotential and enables perfect epitaxial passivation of electrodes. We further demonstrate the use of large current pulses during battery formation to promote 2D inorganic SEI growth and improve capacity retention. These insights offer the potential to tailor desired interphases at the nanoscale for future electrochemical devices.

Design of a self-cleanable multilevel anticounterfeiting interface through covalent chemical modulation.

Counterfeit products have posed a significant threat to consumers safety and the global economy. To address this issue, extensive studies have been exploring the use of coatings with unclonable, microscale features for authentication purposes. However, the ease of readout, and the stability of these features against water, deposited dust, and wear, which are required for practical use, remain challenging. Here we report a novel class of chemically functionalizable coatings with a combination of a physically unclonable porous topography and distinct physiochemical properties (e.g., fluorescence, water wettability, and water adhesion) obtained through orthogonal chemical modifications (i.e., 1,4-conjugate addition reaction and Schiff-base reaction at ambient conditions). Unprecedentedly, a self-cleanable and physically unclonable coating is introduced to develop a multilevel anticounterfeiting interface. We demonstrate that the authentication of the fluorescent porous topography can be verified using deep learning. More importantly, the spatially selective chemical modifications can be read with the naked eye via underwater exposure and UV light illumination. Overall, the results reported in this work provide a facile basis for designing functional surfaces capable of independent and multilevel decryption of authenticity.

Novel neuroprotective pyromeconic acid derivatives with concurrent anti-Aß deposition, anti-inflammatory, and anti-oxidation properties for treatment of Alzheimer's disease.

We synthesized a series of novel pyromeconic acid-styrene hybrid compounds and measured their activities in inhibiting Aß1-42 self-aggregation and promoting disaggregation, and their anti-inflammatory and antioxidant properties. The most potent compound, compound 30, had IC50 values of 11.15 µM and 6.87 µM for inhibition of fibril aggregation and promotion of fibril disaggregation, respectively. Because of its redox metal chelating property, 30 also inhibited Cu2+-induced Aß1-42 fibril aggregation and promoted fibril disaggregation with IC50 of 3.69 µM and 3.35 µM, respectively. Molecular docking demonstrated that 30 interacted with key amino acids of Aß1-42, and the reliability of the complex was confirmed by molecular dynamics. In addition, 30 displayed excellent antioxidative activity (oxygen radical absorbance capacity = 2.65 Trolox equivalents) and moderate anti-inflammatory activity and neuroprotection in cell culture assays. Compound 30 was safe in acute toxicity test in mice, and it exhibited favorable pharmacokinetic properties, particularly, accumulation in the hippocampus (maximum ratio of hippocampus to plasma = 7.12). Compound 30 alleviated cognitive deficits in scopolamine-induced amnesia mice; this property may have been attributed to reducing neuroinflammation by inhibiting ionized calcium binding adapter molecule 1 and glial fibrillary acidic protein expression and reducing oxidative stress by activating the Nrf2/HO-1 signaling pathway. In view of its many properties, we envision that 30 is a promising lead for the treatment of Alzheimer's disease.

Magnetocontrollable droplet mobility on liquid crystal-infused porous surfaces.

Magnetocontrollable droplet mobility on surfaces of both solids and simple fluids have been widely used in a wide range of applications. However, little is understood about the effect of the magnetic field on the wettability and mobility of droplets on structured fluids. Here, we report the manipulation of the dynamic behaviors of water droplets on a film of thermotropic liquid crystals (LCs). We find that the static wetting behavior and static friction of water droplets on a 4'-octyl-4-biphenylcarbonitrile (8CB) film strongly depend on the LC mesophases, and that a magnetic field caused no measurable change to these properties. However, we find that the droplet dynamics can be affected by a magnetic field as it slides on a nematic 8CB film, but not on isotropic 8CB, and is dependent on both the direction and strength of the magnetic field. By measuring the dynamic friction of a droplet sliding on a nematic 8CB film, we find that a magnetic field alters the internal orientational ordering of the 8CB which in turn affects its viscosity. We support this interpretation with a scaling argument using the LC magnetic coherence length that includes (i) the elastic energy from the long-range orientational ordering of 8CB and (ii) the free energy from the interaction between 8CB and a magnetic field. Overall, these results advance our understanding of droplet mobility on LC films and enable new designs for responsive surfaces that can manipulate the mobility of water droplets. Electronic Supplementary Material: Supplementary material (further details of the stability of LCIPS against water-induced dewetting, the interfacial tension and contact angle measurement using a goniometer, the estimation of the thickness of LC wrapping layer at air-water interface on droplets, SEM measurements, the average sliding velocity of a water droplet on 5CB, E7, silicone oil, and mineral oil films with and without a magnetic field, representative force diagram (Fd versus time) of a 3-µL water droplet moving at a speed of 0.1 mm/s on a nematic 8CB film, Fdynamic acting on 3 µL water droplets moving at speeds of 0.1-1 mm/s on an isotropic 8CB film, the calculated magnetic coherence length as a function of the magnitude of the magnetic field applied to the nematic LCIPS, and the apparent advancing and receding contact angles of a moving water droplet on nematic LCIPS as a function of time, and polarized light micrographs (top view) of a nematic 8CB film between two DMOAP-functionalized glass slides before and after applying a horizontal magnetic field) is available in the online version of this article at 10.1007/s12274-022-5318-y.