Nanoplastics exposure-induced mitochondrial dysfunction contributes to disrupted stem cell differentiation in human cerebral organoids.

Nanoplastics are ubiquitous in our daily lives, raising concerns about their potential impact on the human brain. Many studies reported that nanoplastics permeate the blood-brain barrier and influence cellular processes in mouse models. However, the neurotoxic effects of ingesting nanoplastics on human brain remain poorly understood.

Artificial Meshed Vessel-Induced Dimensional Breaking Growth of Human Brain Organoids and Multiregional Assembloids.

Brain organoids are widely used to model brain development and diseases. However, a major challenge in their application is the insufficient supply of oxygen and nutrients to the core region, restricting the size and maturation of the organoids. In order to vascularize brain organoids and enhance the nutritional supply to their core areas, two-photon polymerization (TPP) 3D printing is employed to fabricate high-resolution meshed vessels in this study.

Construction of human 3D striato-nigral assembloids to recapitulate medium spiny neuronal projection defects in Huntington's disease.

The striato-nigral (Str-SN) circuit is composed of medium spiny neuronal projections that are mainly sent from the striatum to the midbrain substantial nigra (SN), which is essential for regulating motor behaviors. Dysfunction of the Str-SN circuitry may cause a series of motor disabilities that are associated with neurodegenerative disorders, such as Huntington's disease (HD). Although the etiology of HD is known as abnormally expanded CAG repeats of the huntingtin gene, treatment of HD remains tremendously challenging.

Inhibition of EHMT1/2 rescues synaptic damage and motor impairment in a PD mouse model.

Epigenetic dysregulation that leads to alterations in gene expression and is suggested to be one of the key pathophysiological factors of Parkinson's disease (PD). Here, we found that α-synuclein preformed fibrils (PFFs) induced histone H3 dimethylation at lysine 9 (H3K9me2) and increased the euchromatic histone methyltransferases EHMT1 and EHMT2, which were accompanied by neuronal synaptic damage, including loss of synapses and diminished expression levels of synaptic-related proteins. Furthermore, the levels of H3K9me2 at promoters in genes that encode the synaptic-related proteins SNAP25, PSD95, Synapsin 1 and vGLUT1 were increased in primary neurons after PFF treatment, which suggests a linkage between H3K9 dimethylation and synaptic dysfunction.

Integration of Magnetic-Field-Directed Self-Assembly-Based Cell Culture and Biosensing Platform for Improving hPSCs-Derived Neurons and Quantitative Detection of Neurotransmitter.

Despite the fact that human neural cell models have played significant roles in both research and cell replacement therapies for neurological diseases, the existing techniques for obtaining neurons from human pluripotent stem cells (hPSCs) are arduous and intricate. Additionally, the evaluation of neuron quality in the natural environment remains deficient. Consequently, we have developed a comprehensive platform utilizing magnetic-field-directed self-assembly (MDSA) of MXenes@FeO (M/F) nanocomposites.

Functional reconstruction of the impaired cortex and motor function by hMGEOs transplantation in stroke.

Stroke is the leading cause of death and long-term disability worldwide. But treatments are not available to promote functional recovery, and efficient therapies need to be investigated. Stem cell-based therapies hold great promise as potential technologies to restore function in brain disorders.

Phospholipase A2-activating protein induces mitophagy through anti-apoptotic MCL1-mediated NLRX1 oligomerization.

Mitochondrial protein homeostasis is fine-tuned by diverse physiological processes such as mitochondria-associated degradation (MAD), which is regulated by valosin-containing protein (VCP) and its cofactors. As a cofactor of VCP, the mutation of phospholipase A-2-activating protein (PLAA) is the genetic cause of PLAA-associated neurodevelopmental disorder (PLAAND). However, the physiological and pathological roles of PLAA in mitochondria remain unclear.

Dysfunction of vesicular storage in young-onset Parkinson's patient-derived dopaminergic neurons and organoids revealed by single cell electrochemical cytometry.

Electrochemical cytometry based on nano-tip microelectrodes was used to quantify the vesicular storage at the single-cell level in human neurons and midbrain organoids which acted as disease models of young-onset Parkinson's disease (YOPD). Human dopaminergic (DA) neurons and midbrain organoids were derived from an induced pluripotent stem cell line from one YOPD patient. We show a significant deficiency in vesicular catecholamine storage and a slower pore forming process on the surface of the microelectrode in the DA neurons derived from the YOPD patient.

Human organoids in basic research and clinical applications.

Organoids are three-dimensional (3D) miniature structures cultured in vitro produced from either human pluripotent stem cells (hPSCs) or adult stem cells (AdSCs) derived from healthy individuals or patients that recapitulate the cellular heterogeneity, structure, and functions of human organs. The advent of human 3D organoid systems is now possible to allow remarkably detailed observation of stem cell morphogens, maintenance and differentiation resemble primary tissues, enhancing the potential to study both human physiology and developmental stage. As they are similar to their original organs and carry human genetic information, organoids derived from patient hold great promise for biomedical research and preclinical drug testing and is currently used for personalized, regenerative medicine, gene repair and transplantation therapy.

Human cerebral organoids establish subcortical projections in the mouse brain after transplantation.

Numerous studies have used human pluripotent stem cell-derived cerebral organoids to elucidate the mystery of human brain development and model neurological diseases in vitro, but the potential for grafted organoid-based therapy in vivo remains unknown. Here, we optimized a culturing protocol capable of efficiently generating small human cerebral organoids. After transplantation into the mouse medial prefrontal cortex, the grafted human cerebral organoids survived and extended projections over 4.

Microelectrode-Based Electrochemical Sensing Technology for in Vivo Detection of Dopamine: Recent Developments and Future Prospects.

Dopamine (DA) is an essential type of neurotransmitter in the central nervous system. DA neurons usually exist as nuclei which are mainly found in the ventral tegmental area (VTN) and substantia nigra pars compacta (SNc). Parkinson's disease, epilepsy, schizophrenia and other diseases are all related to the abnormal metabolism of DA.

An electrochemical and fluorescence dual-signal assay based on FeO@MnO and N-doped carbon dots for determination of hydrogen peroxide.

A novel electrochemical and fluorescence dual-signal assay was developed for the determination of hydrogen peroxide (HO) based on FeO@MnO and N-doped carbon dots (NCDs). FeO@MnO was not only applied as the recognizer for HO but also served as the fluorescence quencher and electrochemical enhancer. This permits the dual-signal readout of the analytical system.