Nature Biomedical Engineering最新文献

Activation of the ion channel transient receptor potential vanilloid 1 (TRPV1), which is integral to pain perception, leads to an expansion of channel width, facilitating the passage of cations and large organic molecules. However, the permeability of TRPV1 channels to water remains uncertain, owing to a lack of suitable tools to study water dynamics. Here, using upconversion nanophosphors to discriminate between H₂O and D₂O, by monitoring water permeability across activated TRPV1 at the single-cell and single-molecule levels, and by combining single-channel current measurements with molecular dynamics simulations, we show that water molecules flow through TRPV1 and reveal a direct connection between water migration, cation flow and TRPV1 functionality. We also show in mouse models of acute or chronic inflammatory pain that the administration of deuterated water suppresses TRPV1 activity, interrupts the transmission of pain signals and mitigates pain without impacting other neurological responses. Solvent-mediated analgesia may inspire alternative options for pain management.

Options for the continuous and non-invasive monitoring of blood pressure are limited. Cuff-based sphygmomanometers are widely available, yet provide only discrete measurements. The clinical gold-standard approach for the continuous monitoring of blood pressure requires an arterial line, which is too invasive for routine use. Wearable ultrasound for the continuous and non-invasive monitoring of blood pressure promises to elevate the quality of patient care, yet the isolated sonographic windows in the most advanced prototypes can lead to inaccurate or error-prone measurements, and the safety and performance of these devices have not been thoroughly evaluated. Here we describe validation studies, conducted during daily activities at home, in the outpatient clinic, in the cardiac catheterization laboratory and in the intensive care unit, of the safety and performance of a wearable ultrasound sensor for blood pressure monitoring. The sensor has closely connected sonographic windows and a backing layer that improves the sensor’s accuracy and reliability to meet the highest requirements of clinical standards. The validation results support the clinical use of the sensor.

Allogeneic chimaeric antigen receptor T cells (allo-CAR T cells) derived from healthy donors could provide rapid access to standardized and affordable batches of therapeutic cells if their rejection by the host’s immune system is avoided. Here, by means of an in vivo genome-wide CRISPR knockout screen, we show that the deletion of Fas or B2m in allo- T cells increases their survival in immunocompetent mice. Human B2M^– allo-CAR T cells become highly sensitive to rejection mediated by natural killer (NK) cells, whereas FAS^– CAR T cells expressing normal levels of human leukocyte antigen I remain resistant to NK cells. CD3^– FAS^– CAR T cells outperformed CD3^– B2M^– CAR T cells in the control of leukaemia growth in mice under allogeneic pressure by T cells and NK cells. The partial protection of CD3^– FAS^– allo-CAR T cells from cellular rejection may improve the efficacy of allogeneic cellular therapies in patients with cancer.

Minimally invasive neural interfaces can be used to diagnose, manage and treat many disorders, with reduced risks of surgical complications. However, endovascular probes lack access to key cortical, subcortical and spinal targets, and are not typically explantable after endothelialization. Here we report the development and testing, in sheep, of endocisternal neural interfaces that approach brain and spinal cord targets through inner and outer spaces filled with cerebrospinal fluid. Thus, the interfaces gain access to the entire brain convexity, to deep brain structures within the ventricles and to the spinal cord from the spinal subarachnoid space. We combined an endocisternal neural interface with wireless miniature magnetoelectrically powered bioelectronics so that it can be freely navigated percutaneously from the spinal space to the cranial subarachnoid space, and from the cranial subarachnoid space to the ventricles. In sheep, we show recording and stimulation functions, as well as repositioning of the flexible electrodes and explantation of the interface after chronic implantation. Minimally invasive endocisternal bioelectronics may enable chronic and transient therapies, particularly for stroke rehabilitation and epilepsy monitoring.

By monitoring brain neural signals, neural recorders allow for the study of neurological mechanisms underlying specific behavioural and cognitive states. However, the large brain volumes of non-human primates and their extensive range of uncontrolled movements and inherent wildness make it difficult to carry out covert and long-term recording and analysis of deep-brain neural signals. Here we report the development and performance of a stealthy neural recorder for the study of naturalistic behaviours in non-human primates. The neural recorder includes a fully implantable wireless and battery-free module for the recording of local field potentials and accelerometry data in real time, a flexible 32-electrode neural probe with a resorbable insertion shuttle, and a repeater coil-based wireless-power-transfer system operating at the body scale. We used the device to record neurobehavioural data for over 1 month in a freely moving monkey and leveraged the recorded data to train an artificial intelligence model for the classification of the animals’ eating behaviours.