Ultraflexible and degradable organic synaptic transistors (OSTs) enable seamless integration with the human body and are capable of disintegrating after completing their specific functions, opening up remarkable new opportunities for “green” electronics in implantable neuromorphic systems, brain‐computer interfaces and wearable artificial intelligence systems. However, it is still an outstanding challenge to realize such synaptic transistors that simultaneously satisfy both ultra flexibility and degradability. The advancement of such electronics critically hinges on the development of ultraflexible and degradable gate dielectrics, which is the vital component to realize synaptic function of transistors. Here, for the first time, a self‐supporting natural dextran membrane is utilized as the gate dielectric to achieve an ultraflexible and degradable OST. The resultant device is only 309 nm thick, and can maintain stable synaptic behavior on various curved surfaces, even on a superfine capillary with the bending radius down to 0.15 mm. After the devices complete their functions, they can rapidly degrade in ambient water without any toxic byproducts, effectively reducing environmental pollution. More strikingly, proton conduction is confirmed to exist in neutral polysaccharides, and the protons originate from the self‐dissociation of water, which provides a meaningful guideline for future synaptic transistors based on neutral natural biomaterials.
Primary progressive aphasia is a neurodegenerative disease that selectively impairs language without equivalent impairment of speech, memory or comportment. In 118 consecutive autopsies on patients with primary progressive aphasia, primary diagnosis was Alzheimer’s disease neuropathological changes (ADNC) in 42%, corticobasal degeneration or progressive supranuclear palsy neuropathology in 24%, Pick’s disease neuropathology in 10%, transactive response DNA binding proteinopathy type A [TDP(A)] in 10%, TDP(C) in 11% and infrequent entities in 3%. Survival was longest in TDP(C) (13.2 ± 2.6 years) and shortest in TDP(A) (7.1 ± 2.4 years). A subset of 68 right-handed participants entered longitudinal investigations. They were classified as logopenic, agrammatic/non-fluent or semantic by quantitative algorithms. Each variant had a preferred but not invariant neuropathological correlate. Seventy-seven per cent of logopenics had ADNC, 56% of agrammatics had corticobasal degeneration/progressive supranuclear palsy or Pick’s disease and 89% of semantics had TDP(C). Word comprehension impairments had strong predictive power for determining underlying neuropathology positively for TDP(C) and negatively for ADNC. Cortical atrophy was smallest in corticobasal degeneration/progressive supranuclear palsy and largest in TDP(A). Atrophy encompassed posterior frontal but not temporoparietal cortex in corticobasal degeneration/progressive supranuclear palsy, anterior temporal but not frontoparietal cortex in TDP(C), temporofrontal but not parietal cortex in Pick’s disease and all three lobes with ADNC or TDP(A). There were individual deviations from these group patterns, accounting for less frequent clinicopathologic associations. The one common denominator was progressive asymmetric atrophy overwhelmingly favouring the left hemisphere language network. Comparisons of ADNC in typical amnestic versus atypical aphasic dementia and of TDP in type A versus type C revealed fundamental biological and clinical differences, suggesting that members of each pair may constitute distinct clinicopathologic entities despite identical downstream proteinopathies. Individual TDP(C) participants with unilateral left temporal atrophy displayed word comprehension impairments without additional object recognition deficits, helping to dissociate semantic primary progressive aphasia from semantic dementia. When common and uncommon associations were considered in the set of 68 participants, one neuropathology was found to cause multiple clinical subtypes, and one subtype of primary progressive aphasia to be caused by multiple neuropathologies, but with different probabilities. Occasionally, expected clinical manifestations of atrophy sites were absent, probably reflecting individual peculiarities of language organization. The hemispheric asymmetry of neurodegeneration and resultant language impairment in primary progressive aphasia reflect complex interactions among the cellular affinities of the degenerative disease, the constitutive biology of language cortex, familial or developmental vulnerabilities of this network and potential idiosyncrasies of functional anatomy in the affected individual.
A series of O-aryl- and alkyl-substituted phosphorodithioates were designed and synthesized as hydrogen sulfide (H2S) donors. H2S released capability of these compounds was evaluated by fluorescence methods. O-aryl substituted donors showed slow and sustained H2S release while O-alkylated compounds showed very weak H2S release capability. We also evaluated donors’ protective effects against hydrogen peroxide (H2O2)-induced oxidative damage in myocytes and donors’ toxicity toward B16BL6 mouse melanoma cells.
The direct use of sulfinic acids as an odorless sulfur source to construct hetroaryl sulfides through a photoredox process has been realized at room temperature for the first time.
3D cell culture has been strongly advocated as a highly useful culture technique instead of the traditional 2D cell culture. Specially, spheroids, as the primary mode of 3D cell culture, allow cells to establish a connection between the cell and the extracellular matrix to form a specific 3D structure that better mimics the growing environment of cells in vivo. Benefiting from the emergence of various advanced micromachining platforms, spheroids have received increasing attention in diverse fields. Herein, the combination of the cell spheroid culture with microfluidic technology is reviewed. After concisely introducing the traditional methods for fabricating cell spheroids, an outline of the approaches for preparing cell spheroids using different advanced techniques is given. Then, the various applications of the generated cell spheroids in the field of biomedical engineering are presented and the current limitations, challenges, and future directions are summarized.
Polysaccharides display poor cell adhesion due to the lack of cell binding domains. This severely limits their applications in regenerative medicine. This study reports novel cross-linked pectin nanofibers with dramatically enhanced cell adhesion. The nanofibers are prepared by at first oxidizing pectin with periodate to generate aldehyde groups and then cross-linking the nanofibers with adipic acid dihydrazide to covalently connect pectin macromolecular chains with adipic acid dihydrazone linkers. The linkers may act as cell binding domains. Compared with traditional Ca-cross-linked pectin nanofibers, the pectin nanofibers with high oxidation/cross-linking degree exhibit much enhanced cell adhesion capability. Moreover, the cross-linked pectin nanofibers exhibit excellent mechanical strength (with Young's modulus ∼10 MPa) and much enhanced body degradability (degrade completely in 3 weeks or longer time). The combination of excellent cell adhesion capability, mechanical strength, and body degradability suggests that the cross-linked pectin nanofibers are promising candidates for in vivo applications such as tissue engineering and wound healing. This cross-linking strategy may also be used to improve the cell adhesion capability of other polysaccharide materials.
Despite significant progress over the past few decades, creating a tissue-engineered vascular graft with replicated functions of native blood vessels remains a challenge due to the mismatch in mechanical properties, low biological function, and rapid occlusion caused by restenosis of small diameter vessel grafts (<6 mm diameter). A scaffold with similar mechanical properties and biocompatibility to the host tissue is ideally needed for the attachment and proliferation of cells to support the building of engineered tissue. In this study, pectin hydrogel nanofiber scaffolds with two different oxidation degrees (25 and 50%) were prepared by a multistep methodology including periodate oxidation, electrospinning, and adipic acid dihydrazide crosslinking. Scanning electron microscopy (SEM) images showed that the obtained pectin nanofiber mats have a nano-sized fibrous structure with 300–400 nm fiber diameter. Physicochemical property testing using Fourier transform infrared (FTIR) spectra, atomic force microscopy (AFM) nanoindentations, and contact angle measurements demonstrated that the stiffness and hydrophobicity of the fiber mat could be manipulated by adjusting the oxidation and crosslinking levels of the pectin hydrogels. Live/Dead staining showed high viability of the mesenchymal stem cells (MSCs) cultured on the pectin hydrogel fiber scaffold for 14 days. In addition, the potential application of pectin hydrogel nanofiber scaffolds of different stiffness in stem cell differentiation into vascular cells was assessed by gene expression analysis. Real-time polymerase chain reaction (RT-PCR) results showed that the stiffer scaffold facilitated the differentiation of MSCs into vascular smooth muscle cells, while the softer fiber mat promoted MSC differentiation into endothelial cells. Altogether, our results indicate that the pectin hydrogel nanofibers have the capability of providing mechanical cues that induce MSC differentiation into vascular cells and can be potentially applied in stem cell-based tissue engineering.
The goal of regenerative wound healing dressings is to restore tissue function back to normal physiological activity and accelerate skin tissue regeneration at wound sites. The optimal strategy to achieve this purpose requires a balance between material functionality, degradation, safety, and tissue regrowth. Herein, for the first time, an ultrasonic-triggered irreversible tending to equilibrium self-assembly and ionic cross-linking codriven strategy is proposed for producing multifunctional cinnamaldehyde-tannic acid-zinc acetate nanospheres (CA-TA-ZA NSs), realizing the fusion of hydrophilic and hydrophobic drug-food small molecules. Moreover, a novel "all-in-one" chitosan (CS)-based hydrogel functionalized by introducing drug-food small molecules self-assembled CA-TA-ZA NSs to the 3D network structures of CS is designed, integrating excellent antibacterial, antioxidant, anti-inflammatory and reducing oxidative stress damage abilities. Additionally, the multifunctional CS-based hydrogel can realize rapid in situ gelation at wound sites and completely cover the irregular wounds. All of these superiorities enable the CS-based hydrogel to clean the wound microenvironment, induce skin tissue remodeling, promote blood vessel repair and hair follicle regeneration, restore the immune system back to normal physiological activity, and accelerate wound healing. Therefore, this study offers a new perspective for the design of advanced functional materials with great application potential in the biomedical field.
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