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Multi-access edge computing (MEC) promises to enable latency-critical applications by bringing computational power closer to mobile devices, but our measurements on commercial MEC deployments reveal frequent SLO violations due to high tail latencies. We identify resource contention at the RAN and the edge server as the root cause, compounded by SLO-unaware schedulers. Existing SLO-aware approaches require RAN--edge coordination, making them impractical for deployment and prone to poor performance due to coordination delays, limited heterogeneous application support, and ignorance of edge resource contention. This paper introduces SMEC, a practical, SLO-aware resource management framework that facilitates deadline-aware scheduling through fully decoupled operations at the RAN and edge servers. Our key insight is that standard 5G protocols and application behaviors naturally provide information exploitable for SLO-aware management without extensive infrastructure or application changes. Evaluation on our 5G MEC testbed shows that SMEC achieves 90--96% SLO satisfaction versus under 6% for existing approaches, while reducing tail latency by up to 122×. We have open-sourced SMEC at https://github.com/smec-project. 

Embedding-based dense retrieval has become the cornerstone of many critical applications, where approximate nearest neighbor search (ANNS) queries are often combined with filters on labels such as dates and price ranges. Graph-based indexes achieve state-of-the-art performance on unfiltered ANNS but encounter connectivity breakdown on low-selectivity filtered queries, where qualifying vectors become sparse and the graph structure among them fragments. Recent research proposes specialized graph indexes that address this issue by expanding graph degree, which incurs prohibitively high construction costs. Given these inherent limitations of graph-based methods, we argue for a dual-index architecture and present Curator, a partition-based index that complements existing graph-based approaches for low-selectivity filtered ANNS. Curator builds specialized indexes for different labels within a shared clustering tree, where each index adapts to the distribution of its qualifying vectors to ensure efficient search while sharing structure to minimize memory overhead. The system also supports incremental updates and handles arbitrary complex predicates beyond single-label filters by efficiently constructing temporary indexes on the fly. Our evaluation demonstrates that integrating Curator with state-of-the-art graph indexes reduces low-selectivity query latency by up to 20.9x compared to pre-filtering fallback, while increasing construction time and memory footprint by only 5.5% and 4.3%, respectively. 

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. 

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.