Hollow covalent organic frameworks (COFs) have gained significant attention because of their specific properties, including enhanced surface-to-volume ratio, large surface area, hierarchical structure, highly ordered nanostructures, and excellent chemical stability. These intrinsic characteristics endow hollow COFs with fascinating physicochemical properties and make them highly attractive for widespread applications, such as catalysis, energy storage, drug delivery, therapy, sensing, and environmental remediation. This review focuses on the recent developments in the synthesis of hollow COFs and their derivatives. In addition, their practical applications in various fields are summarized. Finally, challenges and future opportunities in terms of their synthetic methodologies and practical applications are discussed. Hollow COFs are expected to play an important role in the future of materials science.

Nanoarchitectonics of Hollow Covalent Organic Frameworks: Synthesis and Applications.

ACCESS Metrics & More Article Recommendations ■ CONTENTS Functional Basics of Cas12 and Cas13 208 Nuclease Activity of Cas12a 208 Nuclease Activity of Cas13a 208 Quantitative Determination of trans-Cleavage Kinetics of Cas Enzymes 209 trans-Cleavage Kinetics of Cas12 and Cas13 212 trans-Cleavage Kinetics of Cas12 and Its Contributing Factors 212 trans-Cleavage Kinetics of Cas13 and Its Contributing Factors 212 Nucleic Acid Detection Sensitivity Achieved by trans-Cleavage Activity of Cas Enzymes 213 Relations between the trans-Cleavage Kinetics and the Limit of Detection 213 Prediction of Performance Aided by Machine Learning 214 Challenges of trans-Cleavage and Signal Amplification in Live Cells 214 Concluding Remarks and Perspectives 214 Author Information 215 Corresponding Author 215 Authors 215 Notes 215 Biographies 215 Acknowledgments 215 References 216

https://pubs.acs.org/doi/pdf/10.1021/acs.analchem.2c04555

Signal Amplification by the trans-Cleavage Activity of CRISPR-Cas Systems: Kinetics and Performance

Timely identification of human papillomavirus (HPV) infection is crucial for the prevention of cervical cancer. Current HPV detection methods mainly rely on polymerase chain reaction (PCR), which often requires bulky equipment and a long assay time. In this work, we report a heating-membrane-assisted multiplexed microfluidics platform that couples recombinase polymerase amplification (RPA) and CRISPR technology (termed M3-CRISPR) for fast and low-cost detection of multiple HPV subtypes. The heating membrane can provide convenient temperature control for the on-chip RPA and CRISPR assays. This stand-alone system allows simultaneous detection of HPV16 and HPV18 with high specificity and detection sensitivity (0.5 nM and 1 × 10-18 M for unamplified and amplified plasmids, respectively) in 30 min with a fluorescence-based readout. Furthermore, we introduced an optimized lateral flow dipstick (LFD) into the portable system to allow visualized detection of HPV DNA. The LFD-based readout also reached a detection sensitivity of 1 × 10-18 M for amplified plasmids and realized successful detection of HPV subtypes in the clinical samples. Finally, we established an automatic microfluidic system that enables the sample-in-answer-out detection of HPV subtypes. We believe that this fast, convenient, and affordable molecular diagnostic platform can serve as a useful tool in point-of-care testing of HPV or other pathogens.

Coupling CRISPR/Cas12a and Recombinase Polymerase Amplification on a Stand-Alone Microfluidics Platform for Fast and Parallel Nucleic Acid Detection.

The special structural morphology of hollow covalent organic frameworks (HCOFs) has an important influence on their applications. However, the rapid and precise control of morphology for HCOFs still remains largely challenging. Herein, we present a facile and universal two-step strategy based on solvent evaporation and oxidation of imine bond for the controllable synthesis of HCOFs. The strategy enables to prepare HCOFs in a greatly shortened reaction time and seven kinds of HCOFs are fabricated by the oxidation of imine bond via hydroxyl radicals (•OH) generated from Fenton reaction. Importantly, a fascinating library of HCOFs with diverse nanostructures, including bowl-like, yolk-shell, capsule-like and flower-like morphologies, has been ingeniously constructed. Owing to the large cavities, the obtained HCOFs are ideal candidates for drug delivery, which are employed to load five small molecule drugs, achieving the enhanced sonodynamic cancer therapy in vivo.

Construction of Multiform Hollow-Structured Covalent Organic Frameworks via a Facile and Universal Strategy for Enhanced Sonodynamic Cancer Therapy.

Next-generation biosensing tools based on CRISPR/Cas have revolutionized the molecular detection. A number of CRISPR/Cas-based biosensors have been reported for the detection of nucleic acid targets. The establishment of efficient methods for non-nucleic acid target detection would further broaden the scope of this technique, but up to now, the concerning research is limited. In the current study, we reported a versatile biosensing platform for non-nucleic acid small-molecule detection called SMART-Cas12a (small-molecule aptamer regulated test using CRISPR/Cas12a). Simply, hybridization chain reaction cascade signal amplification was first trigged by functional nucleic acid (aptamer) through target binding. Then, the CRISPR/Cas system was integrated to recognize the amplified products followed by activation of the trans-cleavage. As such, the target can be ingeniously converted to nucleic acid signals and then fluorescent signals that can be readily visualized and analyzed by a customized 3D-printed visualizer with the help of a home-made App-enabled smartphone. Adenosine triphosphate was selected as a model target, and under the optimized conditions, we achieved fine analytical performance with a linear range from 0.1 to 750 μM and a detection limit of 1.0 nM. The satisfactory selectivity and recoveries that we have obtained further demonstrated this method to be suitable for a complex sample environment. The sample-to-answer time was less than 100 min. Our work not only expanded the reach of the CRISPR-Cas system in biosensing but also provided a prototype method that can be generalized for detecting a wider range of analytes with desirable adaptability, sensitivity, specificity, and on-site capability.

Sensitive Small Molecule Aptasensing based on Hybridization Chain Reaction and CRISPR/Cas12a Using a Portable 3D-Printed Visualizer.

http://manuscript.elsevier.com/S0956566322002792/pdf/S0956566322002792.pdf

Hollow covalent organic framework-sheltering CRISPR/Cas12a as an in-vivo nanosensor for ATP imaging.

Block-STM is a parallel execution engine for smart contracts, built around the principles of Software Transactional Memory. Transactions are grouped in blocks, and every execution of the block must yield the same deterministic outcome. Block-STM further enforces that the outcome is consistent with executing transactions according to a preset order, leveraging this order to dynamically detect dependencies and avoid conflicts during speculative transaction execution. At the core of Block-STM is a novel, low-overhead collaborative scheduler of execution and validation tasks. Block-STM is implemented on the main branch of the Diem Blockchain code-base and runs in production at Aptos. Our evaluation demonstrates that Block-STM is adaptive to workloads with different conflict rates and utilizes the inherent parallelism therein. Block-STM achieves up to 110k tps in the Diem benchmarks and up to 170k tps in the Aptos Benchmarks, which is a 20x and 17x improvement over the sequential baseline with 32 threads, respectively. The throughput on a contended workload is up to 50k tps and 80k tps in Diem and Aptos benchmarks, respectively.

pdf/block-stm-scaling-blockchain-execution-by-turning-ordering-2912xl90.pdf

Block-STM: Scaling Blockchain Execution by Turning Ordering Curse to a Performance Blessing

The Narwhal system is a state-of-the-art Byzantine fault-tolerant scalable architecture that involves constructing a directed acyclic graph (DAG) of messages among a set of validators in a Blockchain network. Bullshark is a zero-overhead consensus protocol on top of the Narwhal's DAG that can order over 100k transactions per second. Unfortunately, the high throughput of Bullshark comes with a latency price due to the DAG construction, increasing the latency compared to the state-of-the-art leader-based BFT consensus protocols. We introduce Shoal, a protocol-agnostic framework for enhancing Narwhal-based consensus. By incorporating leader reputation and pipelining support for the first time, Shoal significantly reduces latency. Moreover, the combination of properties of the DAG construction and the leader reputation mechanism enables the elimination of timeouts in all but extremely uncommon scenarios in practice, a property we name Prevalent Responsiveness"(it strictly subsumes the established and often desired Optimistic Responsiveness property for BFT protocols). We integrated Shoal instantiated with Bullshark, the fastest existing Narwhal-based consensus protocol, in an open-source Blockchain project and provide experimental evaluations demonstrating up to 40% latency reduction in the failure-free executions, and up-to 80% reduction in executions with failures against the vanilla Bullshark implementation.

pdf/shoal-improving-dag-bft-latency-and-robustness-375xldss.pdf

Shoal: Improving DAG-BFT Latency And Robustness

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Hollow covalent organic framework-sheltering CRISPR/Cas12a as an in-vivo nanosensor for ATP imaging.

Block-STM: Scaling Blockchain Execution by Turning Ordering Curse to a Performance Blessing

Shoal: Improving DAG-BFT Latency And Robustness