Search for: All records

Not AvaStimuli-responsive polypeptides offer unique advantages for biomedical applications due to their biocompatibility, degradability, and structural tunability. In this study, we report the synthesis of innovative redox-responsive polypeptide-based diblock copolymers consisting of functional disulfide-containing homocysteine derivatives and hydrophobic γ-benzyl-l-glutamate segments via sequential ring-opening polymerizations. The polymerization kinetics revealed that the polymerizations were well-controlled with living characteristics, resulting in diblock copolymers PHcy-b-PBLG with narrow molecular weight distributions. The resulting functional-hydrophobic diblock copolymers were further converted to a variety of pendant chains via thiol–disulfide exchange reactions, yielding amphiphilic polymers with tunable surface charges. These disulfide-linked materials readily self-assembled into nanoparticles in aqueous environments with hydrophobic PBLG forming the core and redox-sensitive PHcy forming the shell. The redox-responsive nanoparticles displayed a narrow size distribution, excellent colloidal stability, and excellent biocompatibility. The disulfide bonds within the polymer backbone confer redox sensitivity, allowing potential cleavage in reducing environments. Owing to their tunable surface functionality, redox-responsiveness, and biocompatibility, this platform provides a versatile route to engineer responsive nanostructures for biomedical applications, for example, positively charged nanoparticles toward nucleic acid delivery.ilable 

Proteolysis-targeting chimera (PROTAC) has emerged as a groundbreaking therapeutic strategy by hijacking the endogenous ubiquitin proteasome system (UPS) for targeted protein degradation. These heterobifunctional molecules recruit E3 ligases to recognize the protein of interest (POI) and facilitate its ubiquitination, leading to subsequent proteasomal degradation. Compared to conventional protein inhibitors, PROTACs offer a broader range of target degradation and remain effective even against proteins with drug-resistant mutations. Moreover, PROTACs function in a catalytic manner to degrade POIs, allowing for significantly lower administration dosages. In recent years, PROTACs have shown great promise in cancer therapy due to their high efficiency and broad applicability. However, their clinical applications remain challenging due to low bioavailability, limited tumor-targeting ability, and potential side effects. Utilizing nanomedicine for the delivery of PROTACs offers a promising strategy to enhance bioavailability, improve tumor selectivity, and minimize toxicity, thereby advancing their applications in cancer treatment. In this review, we outline the fundamental design principles of PROTACs, summarize the latest progress of nanomedicines from molecular design to drug delivery for improved tumor treatment, introduce PROTAC-based combination therapies and emerging design strategies, and discuss current challenges and future prospects of PROTAC nanomedicines toward clinical translation. 

Facing constant challenges from various pathogens and pests, plants have evolved different strategies to defend themselves both locally and systemically. A global change in RNA metabolism is one of the necessary steps to mount a long-lasting immunity against present and future invasions.Arabidopsisserine/arginine-rich 45 (SR45) is an evolutionarily conserved RNA-binding protein that regulates multiple steps of RNA metabolism. Our prior study suggested that SR45 acts as a negative regulator of plant immunity. To better understand the molecular mechanism for SR45’s defense role, we examined the metabolic profile in both Col-0 andsr45-1. The results showed a significant accumulation of pipecolic acid (Pip), salicylic acid (SA), and other potential defense compounds insr45-1, indicating an increased systemic immunity. Thesr45–1mutant exhibited an elevated resistance to a wide range of biotrophic pathogen species and insensitivity to Pip, SA, and pathogen pretreatment. Between the two alternatively spliced isoforms, SR45.1 and SR45.2, SR45.1 seemed to be the culprit for the observed immune suppression. Upon examination of the transcriptome profile between Col-0 andsr45-1under either mock orPseudomonas syringae PmaDG3 challenge, we identified 1,125 genes as SR45-suppressed andPmaDG3-induced. Genes that function in SA biosynthesis and systemic acquired resistance were overrepresented, including those coding for WRKY, receptor-like kinases (RLKs), receptor-like proteins (RLPs), protein kinases, and TIR-NBS-LRR proteins. In addition, we identified significant alternative splicing activity in a list of genes due to eithersr45–1alone or bothsr45–1andPmaDG3 challenge. Among them, we characterized the effect of alternative splicing in two candidates,CBRLK1andSRF1. Interestingly, alternative splicing in both exhibited a switch between RLPs and RLKs in the predicted protein products. Overexpressing theirsr45–1dominant isoform in Col-0 led to a partial increase in immunity, suggesting the involvement of both alternative splicing events in SR45-conferred immune suppression. In summary, we hypothesize that SR45 regulates a subset of immune genes at either transcriptional or co-transcriptional pre-mRNA splicing levels to confer its function in systemic immune suppression. 

Relying on the anharmonic special displacement method, we introduce an ab initio quasistatic polymorphous framework to describe local disorder, anharmonicity, and electron-phonon coupling in superionic conductors. Using cubic Cu2⁢Se, we show that positional polymorphism yields the breakdown of the phonon quasiparticle picture, leading to extremely overdamped anharmonic vibrations while preserving transverse acoustic phonons, consistent with experiments. We also demonstrate highly broadened electronic spectral functions with band gap openings of 1.0 eV due to polymorphism, and that anharmonic electron-phonon coupling leads to a band gap narrowing with increasing temperature. Our approach, relying on generating a handful of configurations, opens the way for efficient calculations in superionic crystals to elucidate their compelling high figure of merit. 

Abstract Current sheets are quasi‐1D layers of strong current density, which play a crucial role in storing magnetic field energy and subsequently releasing it through charged particle acceleration and plasma heating. They are observed in planetary magnetospheres and solar wind flows, where they are also known as solar wind discontinuities. Despite significant variations in plasma parameters across different magnetospheres and the solar wind, current sheet configurations can remain fundamentally similar. In this study, we analyze current sheets observed in various regions, including the near‐Earth (within 30 Earth radii) and distant (50–200 Earth radii) magnetotail, Earth's dayside and nightside magnetosheath, the near‐Earth solar wind, and Martian and Jovian magnetotails. We examine three key plasma parameters: the plasma beta (ratio of plasma to magnetic pressure), the Alfvénic Mach number (ratio of plasma bulk flow speed to Alfvén speed in the current sheet reference frame), and the ion to electron temperature ratio. Additionally, we investigate the kinetic, thermal, and magnetic field energy densities. Our cross‐system analysis demonstrates that the same current sheet configuration can exist across a very wide parametric space spanning multiple orders of magnitude. We also highlight the distinct plasma environments of the Martian and Jovian magnetotails, characterized by large populations of heavy ions, emphasizing their significance in comparative magnetospheric studies. 

Microrobots powered by an external magnetic field could be used for sophisticated medical applications such as cell treatment, micromanipulation, and noninvasive surgery inside the body. Untethered microrobot applications can benefit from haptic technology and telecommunication, enabling telemedical micro-manipulation. Users can manipulate the microrobots with haptic feedback by interacting with the robot operating system remotely in such applications. Artificially created haptic forces based on wirelessly transmitted data and model-based guidance can aid human operators with haptic sensations while manipulating microrobots. The system presented here includes a haptic device and a magnetic tweezer system linked together using a network-based teleoperation method with motion models in fluids. The magnetic microrobots can be controlled remotely, and the haptic interactions with the remote environment can be felt in real time. A time-domain passivity controller is applied to overcome network delay and ensure stability of communication. This study develops and tests a motion model for microrobots and evaluates two image-based 3D tracking algorithms to improve tracking accuracy in various Newtonian fluids. Additionally, it demonstrates that microrobots can group together to transport multiple larger objects, move through microfluidic channels for detailed tasks, and use a novel method for disassembly, greatly expanding their range of use in microscale operations. Remote medical treatment in multiple locations, remote delivery of medication without the need for physical penetration of the skin, and remotely controlled cell manipulations are some of the possible uses of the proposed technology. 

Not AvaDisulfide-containing synthetic polypeptides hold significant promise as biodegradable and biocompatible carriers for controlled drug and gene delivery, enabling triggered therapeutic release with reduced cytotoxicity. However, disulfide incorporation remains challenging, whether through direct polymerization of disulfide-containing monomers or postpolymerization modification. In this work, we present an innovative and simple strategy to incorporate disulfide bonds into polypeptides using ring-opening polymerization of the N-carboxyanhydride of homocysteine, a thiol-containing amino acid. The polymerization was well-controlled, yielding repeating units up to 100 with narrow dispersity. The pendant side chains were readily converted into various GSH-responsive moieties, including anionic, neutral, zwitterionic, and cationic groups, as well as therapeutic agents toward a wide range of biomedical applications. The drug-loaded amphiphilic polymer-drug conjugates displayed triggered release of intact drug and potent anticancer activities. Furthermore, cationic polyhomocysteine derivatives effectively delivered siRNA, eGFP mRNA, and more complex CRISPR components with extremely low cytotoxicity and excellent transfection efficiency.ilable 

van der Waals magnetic materials open up exciting possibilities to investigate fundamental spin properties in low-dimensional systems and to build compact functional spintronic structures. This review focuses on the recent progress in two-dimensional(2D) magnets that explore beyond the homogenous magnetically-ordered state, including magnons (spin waves), magnetic skyrmions, and complex magnetic domains. Properties of these spin and topology excitations in 2D magnets provide insights into spin-orbit interactions and other forms of coupling between electrons, phonons, and spin-dependent excitations. Such spin-based quasiparticles can also serve as information carriers for next-generation high-speed computing elements. We will first lay out the general theoretical basis of dynamical responses in magnetic systems, followed by detailed descriptions of experimental progress in magnons and spin textures (including magnetic domains and skyrmions). Discussion on the experimental techniques and future perspectives are also included.