RESUMEN
Understanding the impact of long-term opioid exposure on the embryonic brain is critical due to the surging number of pregnant mothers with opioid dependency. However, this has been limited by human brain inaccessibility and cross-species differences in animal models. Here, a human midbrain model is established that uses hiPSC-derived midbrain organoids to assess cell-type-specific responses to acute and chronic fentanyl treatment and fentanyl withdrawal. Single-cell mRNA sequencing of 25,510 cells from organoids in different treatment groups reveals that chronic fentanyl treatment arrests neuronal subtype specification during early midbrain development and alters synaptic activity and neuron projection. In contrast, acute fentanyl treatment increases dopamine release but does not significantly alter gene expression related to cell lineage development. These results provide the first examination of the effects of opioid exposure on human midbrain development at the single-cell level.
RESUMEN
The opening of the blood-brain barrier (BBB) by focused ultrasound (FUS) coupled with intravenously injected microbubbles can be leveraged as a form of immunotherapy for the treatment of neurodegenerative disorders. However, how FUS BBB opening affects brain macrophages is not well understood. Here by using single-cell sequencing to characterize the distinct responses of microglia and central nervous system-associated macrophages (CAMs) to FUS-mediated BBB opening in mice, we show that the treatment remodels the immune landscape via the recruitment of CAMs and the proliferation of microglia and via population size increases in disease-associated microglia. Both microglia and CAMs showed early and late increases in population sizes, yet only the proliferation of microglia increased at both timepoints. The population of disease-associated microglia also increased, accompanied by the upregulation of genes associated with gliogenesis and phagocytosis, with the depletion of brain macrophages significantly decreasing the duration of BBB opening.
RESUMEN
We propose an ex vivo T cell expansion system that mimics natural antigen-presenting cells (APCs) for adoptive cell therapy (ACT). Microfiber scaffolds coated with dendritic cell (DC) membrane replicate physicochemical properties of dendritic cells specific for T cell activation such as rapid recognition by T cells, long duration of T cell tethering, and DC-specific co-stimulatory cues. The DC membrane-coated scaffold is first surface-immobilized with T cell stimulatory ligands, anti-CD3 (αCD3) and anti-CD28 (αCD28) antibodies, followed by adsorption of releasable interleukin-2 (IL-2). The scaffolds present both surface and soluble cues to T cells ex vivo in the same way that these cues are presented by natural APCs in vivo. We demonstrate that the DC-mimicking scaffold promotes greater polyclonal expansion of primary human T cells as compared to αCD3/αCD28-functionalized Dynabead. More importantly, major histocompatibility complex molecules derived from the DC membrane of the scaffold allow antigen-specific T cell expansion with target cell-specific killing ability. In addition, most of the expanded T cells (â¼97%) can be harvested from the scaffold by density gradient centrifugation. Overall, the DC-mimicking scaffold offers a scalable, modular, and customizable platform for rapid expansion of highly functional T cells for ACT.
RESUMEN
The COVID-19 pandemic has aggravated a preexisting epidemic: the opioid crisis. Much literature has shown that the circumstances imposed by COVID-19, such as social distancing regulations, medical and financial instability, and increased mental health issues, have been detrimental to those with opioid use disorder (OUD). In addition, unexpected neurological sequelae in COVID-19 patients suggest that COVID-19 compromises neuroimmunity, induces hypoxia, and causes respiratory depression, provoking similar effects as those caused by opioid exposure. Combined conditions of COVID-19 and OUD could lead to exacerbated complications. With limited human in vivo options to study these complications, we suggest that iPSC-derived brain organoid models may serve as a useful platform to investigate the physiological connection between COVID-19 and OUD. This mini-review highlights the advances of brain organoids in other neuropsychiatric and infectious diseases and suggests their potential utility for investigating OUD and COVID-19, respectively.
RESUMEN
We demonstrate optical Nyquist channel generation based on a comb-based optical tapped-delay-line. The frequency lines of an optical frequency comb are used as the taps of the optical tapped-delay-line to perform a finite-impulse response (FIR) filter function. A single optical nonlinear element is utilized to multiplex the taps and form the Nyquist signal. The tunablity of the approach over the baud rate and modulation format is shown. Optical signal-to-noise ratio penalty of 2.8 dB is measured for the 11-tap Nyquist filtering of 32-Gbaud QPSK signal.
RESUMEN
We investigate the orthogonality of orbital angular momentum (OAM) with other multiplexing domains and present a free-space data link that uniquely combines OAM-, polarization-, and wavelength-division multiplexing. Specifically, we demonstrate the multiplexing/demultiplexing of 1008 data channels carried on 12 OAM beams, 2 polarizations, and 42 wavelengths. Each channel is encoded with 100 Gbit/s quadrature phase-shift keying data, providing an aggregate capacity of 100.8 Tbit/s (12×2×42×100 Gbit/s).
RESUMEN
We demonstrate reconfigurable orbital angular momentum (OAM) and polarization manipulation of OAM- and polarization-multiplexed 100 Gbit/s quadrature phase shift keying (QPSK) data channels. Each data channel's OAM value and its polarization state can be arbitrarily changed by taking advantage of the unique wavefront profile of OAM beams using liquid crystal on silicon-based spatial light modulators. The manipulation operation introduces a power penalty of <1 dB for 100 Gbit/s QPSK signals.
