Control of polymers' amorphous-crystalline transition enables miniaturization and multifunctional integration for hydrogel bioelectronics.

Soft bioelectronic devices exhibit motion-adaptive properties for neural interfaces to investigate complex neural circuits. Here, we develop a fabrication approach through the control of metamorphic polymers' amorphous-crystalline transition to miniaturize and integrate multiple components into hydrogel bioelectronics. We attain an about 80% diameter reduction in chemically cross-linked polyvinyl alcohol hydrogel fibers in a fully hydrated state. This strategy allows regulation of hydrogel properties, including refractive index (1.37-1.40 at 480 nm), light transmission (>96%), stretchability (139-169%), bending stiffness (4.6 ± 1.4 N/m), and elastic modulus (2.8-9.3 MPa). To exploit the applications, we apply step-index hydrogel optical probes in the mouse ventral tegmental area, coupled with fiber photometry recordings and social behavioral assays. Additionally, we fabricate carbon nanotubes-PVA hydrogel microelectrodes by incorporating conductive nanomaterials in hydrogel for spontaneous neural activities recording. We enable simultaneous optogenetic stimulation and electrophysiological recordings of light-triggered neural activities in Channelrhodopsin-2 transgenic mice.

Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model.

Fluid flow transport through the trabecular meshwork tissues is a major regulator of intraocular pressure (IOP) modulation in healthy and glaucomatous individuals. Microbead occlusion models of ocular hypertension regulate aqueous humor drainage to induce high IOP to allow for in vivo study of pressure-related glaucomatous pathology. However, the reliability and application of current injectable microbeads are hindered by inadequate design of the beads-tissue interfaces to maintain a stable IOP elevation over the long term. Considering the graded, porous architecture and fluid transport of the trabecular meshwork, we developed a tailored, injectable "viscobeads" technique, which induced a sustained elevation of IOP for at least 8 weeks. These composite viscobeads contain a non-degradable polystyrene (PS) core for structural support and a biodegradable polylactic-co-glycolic acid (PLGA) viscoelastic surface. This approach enhances the obstruction of aqueous humor drainage through heterogeneous sizes of trabecular meshwork fenestrations and reliably modulates the magnitude and duration of ocular hypertension. In a mouse model, a single viscobeads injection resulted in sustained IOP elevation (average 21.4±1.39 mm Hg), leading to a 34% retinal ganglion cell (RGC) loss by 56 days. In an earlier stage of glaucoma progression, we conducted non-invasive electroretinography (ERG) recording and revealed glaucomatous progression by analyzing high-frequency oscillatory potentials. To further explore the application of the viscobeads glaucoma models, we assayed a series of genes through adeno-associated virus (AAV)-mediated screening in mice and assessed the impact of genetic manipulation on RGC survivals. CRISPR mediated disruption of the genes, PTEN, ATF3 and CHOP enhanced RGC survival while LIN 28 disruption negatively impacted RGC survival. This biologically driven viscobeads design provides an accessible approach to investigate chronic intraocular hypertension and glaucoma-like neurodegeneration and ultimately tenders the opportunity to evaluate genetic and pharmacological therapeutics.

Fatigue-resistant hydrogel optical fibers enable peripheral nerve optogenetics during locomotion.

We develop soft and stretchable fatigue-resistant hydrogel optical fibers that enable optogenetic modulation of peripheral nerves in naturally behaving animals during persistent locomotion. The formation of polymeric nanocrystalline domains within the hydrogels yields fibers with low optical losses of 1.07 dB cm-1, Young's modulus of 1.6 MPa, stretchability of 200% and fatigue strength of 1.4 MPa against 30,000 stretch cycles. The hydrogel fibers permitted light delivery to the sciatic nerve, optogenetically activating hindlimb muscles in Thy1::ChR2 mice during 6-week voluntary wheel running assays while experiencing repeated deformation. The fibers additionally enabled optical inhibition of pain hypersensitivity in an inflammatory model in TRPV1::NpHR mice over an 8-week period. Our hydrogel fibers offer a motion-adaptable and robust solution to peripheral nerve optogenetics, facilitating the investigation of somatosensation.

A nanoscale inorganic coating strategy for stabilizing hydrogel neural probes in vivo.

Hydrogels with adaptable optical and mechanical characteristics show considerable promise for light delivery in vivo with neuroengineering applications. However, the unlinked amorphous polymer chains within hydrogels can cause volumetric swelling after water absorption under physiological conditions over time. Chemically cross-linked poly(vinyl alcohol) (PVA) hydrogels showcase fatigue-resistant attributes and promising biocompatibility for the manufacture of soft neural probes. However, possible swelling of the PVA hydrogel matrix could impact the structural stability of hydrogel-based bioelectronics and their long-term in vivo functionality. In this study, we utilized an atomic layer deposition (ALD) technique to generate an inorganic, silicon dioxide (SiO2) coating layer on chemically cross-linked PVA hydrogel fibers. To evaluate the stability of SiO2-coated PVA hydrogel fibers mimicking the in vivo environment, we conducted accelerated stability tests. SiO2-coated PVA hydrogel fibers showed improved stability over a one-week incubation period under a harsh environment, preventing swelling and preserving their mechanical and optical properties compared to uncoated fibers. These SiO2-coated PVA hydrogel fibers demonstrated nanoscale polymeric crystalline domains (6.5 ± 0.1 nm), an elastic modulus of 73.7 ± 31.7 MPa, a maximum elongation of 113.6 ± 24.2%, and minimal light transmission loss (1.9 ± 0.2 dB cm-1). Lastly, we applied these SiO2-coated PVA hydrogel fibers in vivo to optically activate the motor cortex of transgenic Thy1::ChR2 mice during locomotor behavioral tests. This mouse cohort was genetically modified to express the light-sensitive ion channel, channelrhodopsin-2 (ChR2), and implanted with hydrogel fibers to deliver light to the motor cortex area (M2). Light stimulation via hydrogel fibers resulted in optogenetically modulated mouse locomotor behaviors, including increased contralateral rotation, mobility speeds, and travel distances.

Control of Polymers' Amorphous-crystalline Transition for Hydrogel Bioelectronics Miniaturization and Multifunctional Integration.

Bioelectronic devices made of soft elastic materials exhibit motion-adaptive properties suitable for brain-machine interfaces and for investigating complex neural circuits. While two-dimensional microfabrication strategies enable miniaturizing devices to access delicate nerve structures, creating 3D architecture for expansive implementation requires more accessible and scalable manufacturing approaches. Here we present a fabrication strategy through the control of metamorphic polymers' amorphous-crystalline transition (COMPACT), for hydrogel bioelectronics with miniaturized fiber shape and multifunctional interrogation of neural circuits. By introducing multiple cross-linkers, acidification treatment, and oriented polymeric crystalline growth under deformation, we observed about an 80% diameter decrease in chemically cross-linked polyvinyl alcohol (PVA) hydrogel fibers, stably maintained in a fully hydrated state. We revealed that the addition of cross-linkers and acidification facilitated the oriented polymetric crystalline growth under mechanical stretching, which contributed to the desired hydrogel fiber diameter decrease. Our approach enabled the control of hydrogels' properties, including refractive index (RI 1.37-1.40 at 480 nm), light transmission (> 96%), stretchability (95% - 111%), and elastic modulus (10-63 MPa). To exploit these properties, we fabricated step-index hydrogel optical probes with contrasting RIs and applied them in optogenetics and photometric recordings in the mouse brain region of the ventral tegmental area (VTA) with concurrent social behavioral assessment. To extend COMPACT hydrogel multifunctional scaffolds to assimilate conductive nanomaterials and integrate multiple components of optical waveguide and electrodes, we developed carbon nanotubes (CNTs)-PVA hydrogel microelectrodes for hindlimb muscle electromyographic and brain electrophysiological recordings of light-triggered neural activities in transgenic mice expressing Channelrhodopsin-2 (ChR2).

Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells.

Regulatory programs governing neuronal death and axon regeneration in neurodegenerative diseases remain poorly understood. In adult mice, optic nerve crush (ONC) injury by severing retinal ganglion cell (RGC) axons results in massive RGC death and regenerative failure. We performed an in vivo CRISPR-Cas9-based genome-wide screen of 1,893 transcription factors (TFs) to seek repressors of RGC survival and axon regeneration following ONC. In parallel, we profiled the epigenetic and transcriptional landscapes of injured RGCs by ATAC-seq and RNA-seq to identify injury-responsive TFs and their targets. These analyses converged on four TFs as critical survival regulators, of which ATF3/CHOP preferentially regulate pathways activated by cytokines and innate immunity and ATF4/C/EBPγ regulate pathways engaged by intrinsic neuronal stressors. Manipulation of these TFs protects RGCs in a glaucoma model. Our results reveal core transcription programs that transform an initial axonal insult into a degenerative process and suggest novel strategies for treating neurodegenerative diseases.

Microbial composition and nitrogen removal pathways in a novel sequencing batch reactor integrated with semi-fixed biofilm carrier: evidence from a pilot study for low- and high-strength sewage treatment.

The sequencing batch reactor (SBR) activated sludge process is a well-established technology for sewage treatment. One of the drawbacks of SBRs, however, total nitrogen (TN) removals is insufficient. By means of introducing four improvements, including semi-fixed biofilm carrier, sludge elevation mixing and change for the mode of influent and effluent, compliant standard for TN discharge was obtained in this novel SBR configuration during low- and high-strength sewage load. To illustrate the microbial compositions and functions of the attached biofilm on semi-fixed carrier and the suspended aggregates, as well as the nitrogen removal pathway, high throughput 16S rRNA gene amplicon sequencing, PICRUSt2 algorithm, and KEGG database were applied. The results revealed that (i) the microbial communities from suspended aggregates and biofilm samples were significantly different from each other; (ii) during low-strength sewage loads, TN removal was mainly by nitrification-denitrification. The suspended aggregates was responsible for denitrification, while the biofilm was focused on ammonium oxidation; (iii) during high-strength sewage loads, function of nitrate reductase from suspended aggregates was faded, and anammox and N assimilation by biofilm became dominant. Meanwhile, TN removal referring to the formation of L-glutamine via assimilation was the main pathway.

Non-Invasive Electroretinogram Recording with Simultaneous Optogenetics to Dissect Retinal Ganglion Cells Electrophysiological Dynamics.

Electroretinography (ERG) is a non-invasive electrophysiological recording technique that detects the electrical signaling of neuronal cells in the visual system. In conventional ERG recordings, the signals are considered a collective electrical response from various neuronal cell populations, including rods, cones, bipolar cells, and retinal ganglion cells (RGCs). However, due to the limited ability to control electrophysiological responses from different types of cells, the detailed information underlying ERG signals has not been analyzed and interpreted. Linking the features of ERG signals to the specific neuronal response will advance the understanding of neuronal electrophysiological dynamics and provide more evidence to elucidate pathological mechanisms, such as RGC loss during the progression of glaucoma. Herein, we developed an advanced ERG recording system integrated with a programmable, non-invasive optogenetic stimulation method in mice. In this system, we applied an automatic and unbiased ERG data analysis approach to differentiate a, b wave, negative response, and oscillatory potentials. To differentiate the electrophysiological response of RGCs in ERG recordings, we sensitized mouse RGCs with red-light opsin, ChRmine, through adeno-associated virus (AAV) intravitreal injection. Features of RGC dynamics under red-light stimulation were identified in the ERG readout. This non-invasive ERG recording system, associated with the programmable optogenetics stimulation method, provides a new methodology to dissect neural dynamics under variable physiological and pathological conditions in vivo. With the merits of non-invasiveness, improved sensitivity, and specificity, we envision this system can be further applied for early-stage detection of RGC degeneration and functional progression in neural degenerative diseases, such as glaucoma.

Energy-Mediated Machinery Drives Cellular Mechanical Allostasis.

Allostasis is a fundamental biological process through which living organisms achieve stability via physiological or behavioral changes to protect against internal and external stresses, and ultimately better adapt to the local environment. However, an full understanding of cellular-level allostasis is far from developed. By employing an integrated micromechanical tool capable of applying controlled mechanical stress on an individual cell and simultaneously reporting dynamic information of subcellular mechanics, individual cell allostasis is observed to occur through a biphasic process; cellular mechanics tends to restore to a stable state through a mechanoadaptative process with excitative biophysical activity followed by a decaying adaptive phase. Based on these observations, it is found that cellular allostasis occurs through a complex balance of subcellular energy and cellular mechanics; upon a transient and local physical stimulation, cells trigger an allostatic state that maximizes energy and overcomes a mechanical "energy barrier" followed by a relaxation state that reaches its mechanobiological stabilization and energy minimization. Discoveries of energy-driven cellular machinery and conserved mechanotransductive pathways underscore the critical role of force-sensitive cytoskeleton equilibrium in cellular allostasis. This highlight the biophysical origin of cellular mechanical allostasis, providing subcellular methods to understand the etiology and progression of certain diseases or aging.

In situ reversible underwater superwetting transition by electrochemical atomic alternation.

Materials with in situ reversible wettability have attractive properties but remain a challenge to use since the inverse process of liquid spreading is normally energetically unfavorable. Here, we propose a general electrochemical strategy that enables the in situ reversible superwetting transition between underwater superoleophilicity and superoleophobicity by constructing a binary textured surface. Taking the copper/tin system as an example, the surface energy of the copper electrode can be lowered significantly by electrodeposited tin, and be brought back to the initial high-energy state as a result of dissolving tin by removing the potential. Tin atoms with the water depletion layer inhibit the formation of a hydrogen-bonding network, causing oil droplets to spread over the surface, while copper atoms, with a high affinity for hydroxyl groups, facilitate replacing the oil layer with the aqueous electrolyte. The concept is applicable to other systems, such as copper/lead, copper/antimony, gold/tin, gold/lead and gold/antimony, for both polar and nonpolar oils, representing a potentially useful class of switchable surfaces.

In Situ Characterization of the Triphase Contact Line in a Brush-Coating Process: Toward the Enhanced Efficiency of Polymer Solar Cells.

Solution processes have been widely used for making polymer films in organic photoelectric devices but suffer from difficulties in controlling the film formation. Here, by in situ characterization triphase contact lines (TCLs) in a brush-coating process, we clarify how TCLs affect the quality of as-prepared films. By fine-tuning the dewetting of a binary polymer solution (P3HT:PCBM) via different directions, TCLs with different patterns lead to films with different morphologies. High-quality nanothin films with larger crystallized sizes and higher orientations were enabled when TCLs were parallel to the brush edge, based on which the polymer solar cell shows higher power conversion efficiency (2.665%) compared with that of the spin-coated film.

Electrospun γ-Fe2O3 nanofibers as bioelectrochemical sensors for simultaneous determination of small biomolecules.

Nanofibers of α-Fe2O3 and γ-Fe2O3 have been obtained after the controlled calcination of precursor nanofibers synthesized by electrospinning. α-Fe2O3 nanofibers showed an irregular toruloid structure due to the decomposition of poly (4-vinyl) pyridine in air while γ-Fe2O3 nanoparticles decorated nanofibers were observed after the calcination under N2 atmosphere. Electrochemical measurements showed that different electrochemical behaviors were observed on the glassy carbon electrodes modified by α-Fe2O3 and γ-Fe2O3 nanofibers. The electrode modified by γ-Fe2O3 nanofibers exhibited high electrocatalytic activities toward oxidation of dopamine, uric acid and ascorbic acid while α-Fe2O3 nanofibers cannot. Furthermore, the γ-Fe2O3 modified electrode can realize the selective detection of biomolecules in ternary electrolyte solutions. The synthesis of nanofibers of α-Fe2O3 and γ-Fe2O3 and their electrochemical sensing properties relationship have been discussed and analyzed based on the experimental results.

Directional Solution Coating by the Chinese Brush: A Facile Approach to Improving Molecular Alignment for High-Performance Polymer TFTs.

Directional solution coating by the Chinese brush provides a facile approach to fabricate highly oriented polymer thin films by finely controlling the wetting and dewetting processes under directional stress. The biggest advantage of the Chinese brush over the normal western brush is the freshly emergent hairs used, whose unique tapered structure renders a dynamic balance of the liquid within the brush by multiple forces when interacting with the liquid. Consequently, the liquid is steadily held within the brush without any unexpected leakage, making the liquid transfer proceed in a well-controllable manner. It is demonstrated that the Chinese brush coating enables the crystallization of the polymer and the self-assembly of conjugated backbones to proceed in a quasi-steady state via a certain direction, which is attributed to the controllable receding of the three-phase contact line during the dewetting process by the multiple parallel freshly emergent hairs. The as-prepared polymer thin films exhibit over six times higher charge-carrier mobility compared to the spin-coated films, which therefore provides a general approach for high-performance organic thin-film transistors.

Highly Boosted Oxygen Reduction Reaction Activity by Tuning the Underwater Wetting State of the Superhydrophobic Electrode.

By rationally designing superhydrophobic electrodes with different underwater wetting states, it is revealed that only the underwater Wenzel-Cassie coexistent state shows the clearly enhanced ability in catalyzing the oxygen reduction reaction, a typical underwater gas-consuming reaction at electrode. It is proposed that the maximizing and stabilizing the liquid/gas/solid triphase interface, endowed by the underwater Wenzel-Cassie coexistent state, plays a rather crucial role.

Solvothermal Synthesis of Hierarchical Colloidal Nanocrystal Assemblies of ZnFe2O4 and Their Application in Water Treatment.

Hierarchical colloidal nanocrystal assemblies (CNAs) of ZnFe2O4 have been synthesized controllably by a solvothermal method. Hollow ZnFe2O4 spheres can be formed with the volume ratios of ethylene glycol to ethanol of 1:4 in the starting systems, while solid ZnFe2O4 CNAs are obtained by adjusting the volume proportion of ethylene glycol to ethanol from 1:2 to 2:1. Magnetometric measurement data showed that the ZnFe2O4 CNAs obtained with the volume ratios of 1:2 and 1:1 exhibited weak ferromagnetic behavior with high saturation magnetization values of 60.4 and 60.3 emu·g-1, respectively. However, hollow spheres showed a saturation magnetization value of 52.0 emu·g-1, but the highest coercivity among all the samples. It was found that hollow spheres displayed the best ability to adsorb Congo red dye among all the CNAs. The formation mechanisms of ZnFe2O4 CNAs, as well as the relationship between their structure, crystallite size, and properties were discussed based on the experimental results.

Self-removal of condensed water on the legs of water striders.

The ability to control drops and their movements on phobic surfaces is important in printing or patterning, microfluidic devices, and water-repellent materials. These materials are always micro-/nanotextured, and a natural limitation of repellency occurs when drops are small enough (as in a dew) to get trapped in the texture. This leads to sticky Wenzel states and destroys the superhydrophobicity of the material. Here, we show that droplets of volume ranging from femtoliter (fL) to microliter (µL) can be self-removed from the legs of water striders. These legs consist of arrays of inclined tapered setae decorated by quasi-helical nanogrooves. The different characteristics of this unique texture are successively exploited as water condenses, starting from self-penetration and sweeping effect along individual cones, to elastic expulsion between flexible setae, followed by removal at the anisotropic leg surface. We envision that this antifogging effect at a very small scale could inspire the design of novel applicable robust water-repellent materials for many practical applications.

Bio-inspired direct patterning functional nanothin microlines: controllable liquid transfer.

Developing a general and low-cost strategy that enables direct patterning of microlines with nanometer thickness from versatile liquid-phase functional materials and precise positioning of them on various substrates remains a challenge. Herein, with inspiration from the oriental wisdom to control ink transfer by Chinese brushes, we developed a facile and general writing strategy to directly pattern various functional microlines with homogeneous distribution and nanometer-scale thickness. It is demonstrated that the width and thickness of the microlines could be well-controlled by tuning the writing method, providing guidance for the adaptation of this technique to various systems. It is also shown that various functional liquid-phase materials, such as quantum dots, small molecules, polymers, and suspensions of nanoparticles, could directly write on the substrates with intrinsic physicochemical properties well-preserved. Moreover, this technique enabled direct patterning of liquid-phase materials on certain microdomains, even in multiple layered style, thus a microdomain localized chemical reaction and the patterned surface chemical modification were enabled. This bio-inspired direct writing device will shed light on the template-free printing of various functional micropatterns, as well as the integrated functional microdevices.

In situ wetting state transition on micro- and nanostructured surfaces at high temperature.

We studied the in situ transition of the droplets' wetting state on the heated solid surfaces. The wetting behaviors of four micro- and nanostructured surfaces with different chemical components were studied. These parameters included the maximum contact areas (MCA), the maximum evaporation areas (MEA) and the wetting transition temperature (T(trans)). The reduction in MEAs has a specific transition process from wetting (Wenzel state) or partial wetting (Wenzel-Cassie intermediate state) to nonwetting (Cassie State) as the surface temperature rises. When the MEAs drop to zero at a critical temperature (T(trans)), the droplets rebound from the heated surfaces to complete the wetting transition process. The chemical compounds and the surfaces' rough structure play an important role in the droplets' wetting transition behavior. Before FAS-modification, microstructures can increase the MCAs, MEAs, and T(trans). However, the microstructures are less effective at increasing the MEAs and T(trans) than changes to nanostructures. After FAS-modification, both the nano- and microstructures reduce the T(trans). On the FAS-MNSi surfaces, the MEAs are always zero--the droplets rebounded at room temperature, and the wetting transition did occur. We propose two high-temperature mechanisms to explain these transition phenomena.

Bio-inspired multistructured conical copper wires for highly efficient liquid manipulation.

Animal hairs are typical structured conical fibers ubiquitous in natural system that enable the manipulation of low viscosity liquid in a well-controlled manner, which serves as the fundamental structure in Chinese brush for ink delivery in a controllable manner. Here, drawing inspiration from these structure, we developed a dynamic electrochemical method that enables fabricating the anisotropic multiscale structured conical copper wire (SCCW) with controllable conicity and surface morphology. The as-prepared SCCW exhibits a unique ability for manipulating liquid with significantly high efficiency, and over 428 times greater than its own volume of liquid could be therefore operated. We propose that the boundary condition of the dynamic liquid balance behavior on conical fibers, namely, steady holding of liquid droplet at the tip region of the SCCW, makes it an excellent fibrous medium to manipulate liquid. Moreover, we demonstrate that the titling angle of the SCCW can also affect its efficiency of liquid manipulation by virtue of its mechanical rigidity, which is hardly realized by flexible natural hairs. We envision that the bio-inspired SCCW could give inspiration in designing materials and devices to manipulate liquid in a more controllable way and with high efficiency.