Novel wine in an old bottle:Preventive and therapeutic potentials of andrographolide in atherosclerotic cardiovascular diseases

Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound(‘old bottle’)as a novel drug(‘novel wine’)for the prevention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.

DNA Reaction Network Mimicking the Basic Steps of Synaptic Communication

Biological systems use intricate networks of chemical reactions to exchange information. How to simulate complex systems with simple strand-displacement reactions is crucial to broaden the application scenario of the DNA reaction network. Here, we report the artificial DNA reaction network to mimic the operation and function of biological information transfer via strand-displacement reaction. DNA is used as simple artificial analogs to schematize structures and transmit information. Using chemical synapses in neural networks as an example, we show that the proposed network enables core functions of biological systems, such as the long-term potential of synapses, which underpin learning and memory. Also, we performed the simple “silicon mimetic” to link electronic circuits to chemical network-based biological structures. As such, synaptic communication simulated by the DNA reaction network provides a complete demonstration for designing artificial reaction networks based on the essence of information interaction.

Decoupled Two-Phase Framework for Class-Incremental Few-Shot Named Entity Recognition

Class-Incremental Few-Shot Named Entity Recognition(CIFNER)aims to identify entity categories that have appeared with only a few newly added(novel)class examples.However,existing class-incremental methods typically introduce new parameters to adapt to new classes and treat all information equally,resulting in poor generalization.Meanwhile,few-shot methods necessitate samples for all observed classes,making them difficult to transfer into a class-incremental setting.Thus,a decoupled two-phase framework method for the CIFNER task is proposed to address the above issues.The whole task is converted to two separate tasks named Entity Span Detection(ESD)and Entity Class Discrimination(ECD)that leverage parameter-cloning and label-fusion to learn different levels of knowledge separately,such as class-generic knowledge and class-specific knowledge.Moreover,different variants,such as the Conditional Random Field-based(CRF-based),word-pair-based methods in ESD module,and add-based,Natural Language Inference-based(NLI-based)and prompt-based methods in ECD module,are investigated to demonstrate the generalizability of the decoupled framework.Extensive experiments on the three Named Entity Recognition(NER)datasets reveal that our method achieves the state-of-the-art performance in the CIFNER setting.

Probing and modulating the interactions of the DNAzyme with DNA-functionalized nanoparticles

DNA-functionalized gold nanoparticles are one of the most versatile bionanomaterials for biomedical and clinical diagnosis. Herein, we discovered that the performance of DNAzyme cleaving the substrate is highly related to its length. This intriguing phenomenon only appears at the interfaces of DNAfunctionalized gold nanoparticles. We systematically investigated the causes of this phenomenon. We conjectured that the DNAzyme with extended nucleotides that do not match its substrate strand is vulnerable to non-specific adsorption, electrostatic repulsion, and steric hindrance. Based on our improved understanding of this phenomenon, we have successfully developed a highly sensitive and specific amplifiable biosensor to detect human apurinic/apyrimidinic endonuclease 1.

Allosteric DNAzyme-based encoder for molecular information transfer

Dynamic DNA nanotechnology plays a significant role in nanomedicine and information science due to its high programmability based on Watson-Crick base pairing and nanoscale dimensions.Intelligent DNA machines and networks have been widely used in various fields,including molecular imaging,biosensors,drug delivery,information processing,and logic operations.Encoders serve as crucial components for information compilation and transfer,allowing the conversion of information from diverse application scenarios into a format recognized and applied by DNA circuits.However,there are only a few encoder designs with DNA outputs.Moreover,the molecular priority encoder is hardly designed.In this study,we introduce allosteric DNAzyme-based encoders for information transfer.The design of the allosteric domain and the recognition arm allows the input and output to be independent of each other and freely programmable.The pre-packaged mode design achieves uniformity of baseline dynamics and dynamics controllability.We also integrated non-nucleic acid molecules into the encoder through the aptamer design of the allosteric domain.Furthermore,we developed the 2^(n)-n encoder and the EndoⅣ-assisted priority encoder inspired by immunoglobulin's molecular structure and effector patterns.To our knowledge,the proposed encoder is the first enzyme-free DNA encoder with DNA output,and the priority encoder is the first molecular priority encoder in the DNA reaction network.Our encoders avoid complex operations on a single molecule,and their simple structure facilitates their application in complex DNA circuits and biological scenarios.