Self-healing photoluminescent polymers with photosensitive behavior for information storage and multiple-level dynamic encryption.

Photo-responsive luminescent materials capable of responding to light stimuli are crucial in the realm of sophisticated encryption, anti-counterfeiting, and optical data storage. Yet, the development of such materials that also feature self-healing capabilities, swift reaction times, light weight, fatigue resistance, dynamic display abilities, and enhanced security measures is exceedingly rare and presents considerable challenges. Herein, a novel family of self-healing and photo-stimuli-responsive photoluminescent polymers are reported, which is achieved by interlinking terpyridine- and spiropyran-functionalized polymers through N-Ln coordination bonds and hydrogen bonding among the polymer chains. The resulting polymers exhibit good processability, superior tensile strength, fast self-healing ability, and photo-stimuli-responsive performance. The photo-stimuli-responsive properties include unique color shifts (colorless and purple) and light-controlled time-dependent fluorescence modulation (green-, red-, and yellow-emission), which stem from fine-tuning the isomerization of spiropyran and leveraging the fluorescence resonance energy transfer (FRET) from Ln-Tpy donors to spiropyran acceptors, respectively. Besides, these polymers have been successfully applied in dynamic multi-level information encryption applications. We are convinced that these smart materials, crafted through our innovative approach, hold vast potential for applications in information storage, cutting-edge anti-counterfeiting encryption, UV-sensing, and light-writing technologies, marking a novel strategy in the design of photosensitive luminescent smart materials.

Multi-Functional Lanthanide Metallopolymer: Self-Healing and Photo-Stimuli-Responsive Dual-Emitting Luminescence for Diverse Applications.

Photoluminescent metallopolymers displaying photo-stimuli-responsive properties are emerging as promising materials with versatile applications in photo-rewritable patterns, wearable UV sensors, and optical encryption anti-counterfeiting. However, integrating these materials into practical applications that require fast response times, lightweight qualities, fatigue resistance, and multiple encryption capabilities poses challenges. In this study, luminescent photochromic lanthanide (Ln) metallopolymers with rapid self-healing properties are developed by cross-linking terpyridine (Tpy)- and spiropyran (SP)- functionalized polyurethane chains through Ln-Tpy coordination bonds and H-bonds among polymer chains. The resulting products exhibit a range of intriguing features: i) photo-stimuli responsiveness using spiropyran monomers without additional dopants; ii) dual-emitting performance under UV-light due to Ln-Tpy and open-ring spiropyran moieties; iii) satisfactory mechanical properties and self-healing abilities from polymer chains; iv) multiple control switches for luminescence colors through photostimulation or feed ratio adjustments. Leveraging these attributes, the developed material introduces novel opportunities for light-writing applications, advanced information encryption, UV-sensing wearable devices, and insights into designing multifunctional intelligent materials for the future.

Continuous immunosuppression is required for suppressing immune responses to xenografts in non-human primate brains.

Continuous immunosuppression has been widely used in xenografts into non-human primate brains. However, how immune responses change after transplantation in host brains under continuous immunosuppressive administration and whether immunosuppression can be withdrawn to mitigate side effects remain unclear. Human induced neural stem/progenitor cells (iNPCs) have shown long-term survival and efficient neuronal differentiation in primate brains. Here, we evaluate the immune responses in primate brains triggered by human grafts. The results show that the immune responses, including the evident activation of microglia and the strong infiltration of lymphocytes (both T- and B-cells), are caused by xenografts at 4 months post transplantation (p.t.), but significantly reduced at 8 months p.t. under continuous administration of immunosuppressant Cyclosporin A. However, early immunosuppressant withdrawal at 5 months p.t. results in severe immune responses at 10 months p.t. These results suggest that continuous long-term immunosuppression is required for suppressing immune responses to xenografts in primate brains.

The therapeutic prospects and challenges of human neural stem cells for the treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder associated with aging. Due to its insidious onset, protracted progression, and unclear pathogenesis, it is considered one of the most obscure and intractable brain disorders, and currently, there are no effective therapies for it. Convincing evidence indicates that the irreversible decline of cognitive abilities in patients coincides with the deterioration and degeneration of neurons and synapses in the AD brain. Human neural stem cells (NSCs) hold the potential to functionally replace lost neurons, reinforce impaired synaptic networks, and repair the damaged AD brain. They have therefore received extensive attention as a possible source of donor cells for cellular replacement therapies for AD. Here, we review the progress in NSC-based transplantation studies in animal models of AD and assess the therapeutic advantages and challenges of human NSCs as donor cells. We then formulate a promising transplantation approach for the treatment of human AD, which would help to explore the disease-modifying cellular therapeutic strategy for the treatment of human AD.

Synthetic amyloid-ß oligomers drive early pathological progression of Alzheimer's disease in nonhuman primates.

As an insidious and slowly progressive neurodegenerative disorder, Alzheimer's disease (AD) uniquely develops in humans but fails in other species. Therefore, it has been challenged to rebuild human AD in animals, including in non-human primates. Here, we bilaterally delivered synthetic Aß oligomers (AßOs) into the cerebral parenchyma of cynomolgus monkeys, which rapidly drove the formation of massive Aß plaques and concomitant neurofibrillary tangles in the cynomolgus brain. The amyloid and tau pathology as well as their co-occurrence in AßO-monkeys were reminiscent of those in patients with AD. In addition, the activated astrocytes and microglia surrounding Aß plaques indicated the triggered neuroinflammation. The degenerative neurons and synapses around Aß plaques also emerged in cynomolgus brain. Together, soluble AßOs caused the cascade of pathologic events associated with AD in monkeys as occurred in patients at the early phase, which could facilitate the development of a promising animal model for human AD in non-human primates.

Protocol for generating human induced neural progenitor cells from immobilized adult peripheral blood.

Generating induced neural stem/progenitor cells (iNPCs) from somatic cells for medical applications has remained challenging. Here, we describe a reliable protocol to make human iNPCs from a small volume of immobilized adult peripheral blood by direct reprogramming. We have verified that the integration-free human iNPCs can efficiently differentiate into mature neurons in mouse brain upon transplantation and display capacities to functionally replace the damaged neurons, suggesting their potential as donor cells in developing replacement medicine for neurodegenerative diseases. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2019).

Probing the therapeutic potential of TRPC6 for Alzheimer's disease in live neurons from patient-specific iPSCs.

The induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to model and study Alzheimer's disease (AD) under patient-specific genetic background. The lower expression of transient receptor potential canonical 6 (TRPC6) was associated with AD patients, which might be involved in AD pathogenesis. However, the role of TRPC6 that played in AD process still needs more investigation in patient-relevant neurons. In this study, the iPSCs were generated from peripheral blood cells of sporadic AD patients and efficiently differentiated into mature cortical neurons. These sporadic AD-bearing neurons displayed higher levels of AD pathological markers Aß and phospho-tau, but lower levels of TRPC6, than those of control neurons. Treatment of AD neurons with TRPC6 protein fragment or agonist inhibited the elevation of Aß and phospho-tau. Our results in live AD neurons manifest that the compromised expression of TRPC6 substantially contributed to Aß pathology of sporadic AD, suggesting that targeting TRPC6 could help to develop novel therapeutic strategies for the treatments of AD.

Human Neural Stem Cells Reinforce Hippocampal Synaptic Network and Rescue Cognitive Deficits in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by memory impairments in its earliest clinical phase. The synaptic loss and dysfunction leading to failures of synaptic networks in AD brain directly cause cognitive deficits of patient. However, it remains unclear whether the synaptic networks in AD brain could be repaired. In this study, we generated functional human induced neural progenitor/stem cells (iNPCs) that had been transplanted into the hippocampus of immunodeficient wild-type and AD mice. The grafted human iNPCs efficiently differentiated into neurons that displayed long-term survival, progressively acquired mature membrane properties, formed graft-host synaptic connections with mouse neurons and functionally integrated into local synaptic circuits, which eventually reinforced and repaired the neural networks of host hippocampus. Consequently, AD mice with human iNPCs exhibited enhanced synaptic plasticity and improved cognitive abilities. Together, our results suggest that restoring synaptic failures by stem cells might provide new directions for the development of novel treatments for human AD.

ESC-Derived Basal Forebrain Cholinergic Neurons Ameliorate the Cognitive Symptoms Associated with Alzheimer's Disease in Mouse Models.

Degeneration of basal forebrain cholinergic neurons (BFCNs) is associated with cognitive impairments of Alzheimer's disease (AD), implying that BFCNs hold potentials in exploring stem cell-based replacement therapy for AD. However, studies on derivation of BFCNs from embryonic stem cells (ESCs) are limited, and the application of ESC-derived BFCNs remains to be determined. Here, we report on differentiation approaches for directing both mouse and human ESCs into mature BFCNs. These ESC-derived BFCNs exhibit features similar to those of their in vivo counterparts and acquire appropriate functional properties. After transplantation into the basal forebrain of AD model mice, ESC-derived BFCN progenitors predominantly differentiate into mature cholinergic neurons that functionally integrate into the endogenous basal forebrain cholinergic projection system. The AD mice grafted with mouse or human BFCNs exhibit improvements in learning and memory performances. Our findings suggest a promising perspective of ESC-derived BFCNs in the development of stem cell-based therapies for treatment of AD.