Search

Heparan sulfate (HS) is a major component of cell surface glycocalyx with extensive negative charges and plays a protective role by preventing toxins, including small molecule drugs and anticancer cationic lytic peptides (ACLPs), from cells. However, this effect may compromise the treatment efficiency of anticancer drugs. To overcome the impedance of cancer cell glycocalyx, an HS-targeting ACLP PTP-7z was designed by fusion of an ACLP and a Zn 2+ -binding HS-targeting peptide. Upon Zn 2+ ion binding, PTP-7z could self-assemble into uniform nanoparticles and show improved serum stability and reduced hemolysis, which enable it to self-deliver to tumor sites. The peptide PTP-7z showed a pH- and Zn 2+ ion-dependent HS-binding ability, which triggers the HS-induced in situ self-assembling on the cancer cell surface in the acidic tumor microenvironment (TME). The self-assembled PTP-7z can overcome the impedance of cell glycocalyx by either disrupting cell membranes or translocating into cells through endocytosis and inducing cell apoptosis. Moreover, PTP-7z can also inhibit cancer cell migration. These results proved that HS-responsive in situ self-assembling is a practical strategy to overcome the cancer cell glycocalyx barrier for ACLPs and could be extended to the design of other peptide drugs to promote their in vivo application.

Nitric oxide (NO) enhanced photodynamic therapy (PDT) is a promising approach to overcome drug tolerance and resistance to biofilm but is limited by its short excitation wavelengths and low yield of reactive oxygen species (ROS). Herein, we develop a compelling degradable polymer-based near-infrared II (NIR-II, 1000-1700 nm) photosensitizer (PNIR-II), which can maintain 50 % PDT efficacy even under a 2.6 cm tissue barrier. Remarkably, PNIR-II is synthesized by alternately connecting the electron donor thiophene to the electron acceptors diketopyrrolopyrrole (DPP) and boron dipyrromethene (BODIPY), where the intramolecular charge transfer properties can be tuned to increase the intersystem crossover rate and decrease the internal conversion rate, thereby stabilizing the NIR-II photodynamic rather than photothermal effect. For exerting a combination therapy to eradicate multidrug-resistant biofilms, PNIR-II is further assembled into nanoparticles (NPs) with a synthetic glutathione-triggered NO donor polymer. Under 1064 nm laser radiation, NPs precisely release ROS and NO that triggered by over-expressed GSH in the biofilm microenvironment, thereby forming more bactericidal reactive nitrogen species (RNS) in vitro and in vivo in the mice model that orderly destroy biofilm of multidrug-resistant Staphylococcus aureus cultures from clinical patients. It thus provides a new outlook for destroy the biofilm of deep tissues., Competing Interests: We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. There are no conflicts of interest to declare., (© 2023 The Authors.)

Previous works in Brain-Machine Interfaces (BMI) have mostly used a single Kalman filter decoder for deriving continuous kinematics in the complete execution of behavioral tasks. A linear dynamical system may not be able to generalize the sequence whose dynamics changes over time. Examples of such data include human motion such as walking, running, and dancing each of which exhibit complex constantly evolving dynamics. Switching linear dynamical systems (S-LDSs) are powerful models capable of describing a physical process governed by state equations that switch from time to time. The present work demonstrates the motion-state-dependent adaptive decoding of hand and arm kinematics in four different behavioral tasks. Single-unit neural activities were recorded from cortical ensembles in the ventral and dorsal premotor (PMv and PMd) areas of a trained rhesus monkey during four different reach-to-grasp tasks. We constructed S-LDSs for decoding of continuous hand and arm kinematics based on different epochs of the experiments, namely, baseline, pre-movement planning, movement, and final fixation. Average decoding accuracies as high as 89.9%, 88.6%, 89.8%, 89.4%, were achieved for motion-state-dependent decoding across four different behavioral tasks, respectively (p<0.05); these results are higher than previous works using a single Kalman filter (accuracy: 0.83). These results demonstrate that the adaptive decoding approach, or motion-state-dependent decoding, may have a larger descriptive capability than the decoding approach using a single decoder. This is a critical step towards the development of a BMI for adaptive neural control of a clinically viable prosthesis.

Cardiac arrest (CA) can produce complex changes in somatosensory evoked potentials (SSEPs). Somatosensory evoked potentials (SSEPs) indicate the intactness of somatosensory pathways and are commonly used for brain function monitoring during surgeries. Multiresolution biorthogonal wavelet analysis was applied to SSEPs recorded during established CA experiments and post-CA long-term recovery periods in rats. Our results showed that during the first 4 hours after CA, the amplitudes of SSEP, defined here as the difference between the amplitudes of P23 and N20, decreased greatly while the inter-peak latencies between N20 and P23 increased greatly. In the long-term recovery period (within 72 hours), both the amplitudes of SSEPs and the interpeak latencies returned to the baseline. Our results suggest that the changes of SSEPs may represent the post-CA neurological injuries and recovery in the somatosensory afferent pathways. The results here lay ground work for establishing the relationship between SSEPs and post-CA neurological injuries and functional outcomes as well as deploying SSEP in clinical settings to monitor patients resuscitated from CA in the future.