Magnetically Manipulated Optoelectronic Hybrid Microrobots for Optically Targeted Non-Genetic Neuromodulation.

Optically controlled neuromodulation is a promising approach for basic research of neural circuits and the clinical treatment of neurological diseases. However, developing a non-invasive and well-controllable system to deliver accurate and effective neural stimulation is challenging. Micro/nanorobots have shown great potential in various biomedical applications because of their precise controllability. Here, a magnetically-manipulated optoelectronic hybrid microrobot (MOHR) is presented for optically targeted non-genetic neuromodulation. By integrating the magnetic component into the metal-insulator-semiconductor junction design, the MOHR has excellent magnetic controllability and optoelectronic properties. The MOHR displays a variety of magnetic manipulation modes that enables precise and efficient navigation in different biofluids. Furthermore, the MOHR could achieve precision neuromodulation at the single-cell level because of its accurate targeting ability. This neuromodulation is achieved by the MOHR's photoelectric response to visible light irradiation, which enhances the excitability of the targeted cells. Finally, it is shown that the well-controllable MOHRs effectively restore neuronal activity in neurons damaged by ß-amyloid, a pathogenic agent of Alzheimer's disease. By coupling precise controllability with efficient optoelectronic properties, the hybrid microrobot system is a promising strategy for targeted on-demand optical neuromodulation.

Beyond fundamental resonance mode: high-order multi-band ALN PMUT for in vivo photoacoustic imaging.

This paper reports on an aluminum nitride (AlN) piezoelectric micromachined ultrasound transducer (PMUT) array for photoacoustic (PA) imaging, where the high-order resonance modes of the PMUT are utilized to improve imaging resolution. A flexural vibration mode (FVM) PMUT is fabricated and applied in a photoacoustic imaging (PAI) system. Specifically, the microelectromechanical system (MEMS)-based PMUT is suitable for PA endoscopic imaging of blood vessels and bronchi due to its miniature size and high sensitivity. More importantly, AlN is a nontoxic material, which makes it harmless for biomedical applications. In the PAI system, the AlN PMUT array is used to detect PA signals, and the acousto-mechanical response is designed and optimized at the PMUT's fundamental resonance. In this work, we focus on the high-order resonance performance of the PMUT PAI beyond the fundamental resonance. The acoustic and electrical responses of the PMUT's high-order resonance modes are characterized and analyzed. The fundamental and three high-order resonance bandwidths are 2.2, 8.8, 18.5, and 48.2 kHz. Compared with the resolution at the fundamental resonance mode, the resolutions at third- and fourth-order resonance modes increase by 38.7% and 76.9% in a phantom experiment. The high-order resonance modes of the AlN PMUT sensor array provide higher central frequency and wider bandwidth for PA signal detection, which increase the resolution of PAI compared to the PMUT working at the fundamental resonance mode.

Bioinformatics and systems biology approach to identify the pathogenetic link of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Background: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global crisis. Although many people recover from COVID-19 infection, they are likely to develop persistent symptoms similar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after discharge. Those constellations of symptoms persist for months after infection, called Long COVID, which may lead to considerable financial burden and healthcare challenges. However, the mechanisms underlying Long COVID and ME/CFS remain unclear. Methods: We collected the genes associated with Long COVID and ME/CFS in databases by restricted screening conditions and clinical sample datasets with limited filters. The common genes for Long COVID and ME/CFS were finally obtained by taking the intersection. We performed several advanced bioinformatics analyses based on common genes, including gene ontology and pathway enrichment analyses, protein-protein interaction (PPI) analysis, transcription factor (TF)-gene interaction network analysis, transcription factor-miRNA co-regulatory network analysis, and candidate drug analysis prediction. Results: We found nine common genes between Long COVID and ME/CFS and gained a piece of detailed information on their biological functions and signaling pathways through enrichment analysis. Five hub proteins (IL-6, IL-1B, CD8A, TP53, and CXCL8) were collected by the PPI network. The TF-gene and TF-miRNA coregulatory networks were demonstrated by NetworkAnalyst. In the end, 10 potential chemical compounds were predicted. Conclusion: This study revealed common gene interaction networks of Long COVID and ME/CFS and predicted potential therapeutic drugs for clinical practice. Our findings help to identify the potential biological mechanism between Long COVID and ME/CFS. However, more laboratory and multicenter evidence is required to explore greater mechanistic insight before clinical application in the future.

Multidimensional single-cell analysis of human peripheral blood reveals characteristic features of the immune system landscape in aging and frailty.

Frailty is an intermediate status of the human aging process, associated with decompensated homeostasis and death. The immune phenotype of frailty and its underlying cellular and molecular processes remain poorly understood. We profiled 114,467 immune cells from cord blood, young adults and healthy and frail old adults using single-cell RNA and TCR sequencing. Here we show an age-dependent accumulation of transcriptome heterogeneity and variability in immune cells. Characteristic transcription factors were identified in given cell types of specific age groups. Trajectory analysis revealed cells from non-frail and frail old adults often fall into distinct paths. Numerous TCR clonotypes were shared among T-cell subtypes in old adults, indicating differential pluripotency and resilience capabilities of aged T cells. A frailty-specific monocyte subset was identified with exclusively high expression of long noncoding RNAs NEAT1 and MALAT1. Our study discovers human frailty-specific immune cell characteristics based on the comprehensive dimensions in the immune landscape of aging and frailty.