Toward understanding the role of genomic repeat elements in neurodegenerative diseases

Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

Constructing Artificial Nucleobase Compilation to Enable Precise Molecular Medicine

Nucleic acids are the hereditary information storage medium of life. Due to its high programmability and good biocompatibility, the applications of nucleic acids are not limited to their natural function. However, the efficiency of nucleic acids is often hampered by inherent limitations in numerous practical applications, including limited access to complex functional patterns due to only four building blocks, facile degradation by nucleases, rapid renal clearance, poor pharmacokinetic properties, and so on. To end this, the researchers developed unnatural base pairs (UBPs) and numerous artificial analogues of nucleosides and oligonucleotides in recent decades. The developed UBPs and nucleoside base analogues together constitute artificial nucleobase compilation, which promotes the development of biomedical sciences. Here, we describe the development of artificial nucleobase compilation and summarized its applications in precise molecular medicine, including PCR-based diagnostics, aptamer-based diagnostics, nucleobase analogue drugs construction, ASO modification, aptamer-based therapeutics and biomaterials construction. This review provides an overview of current opportunities and challenges of artificial nucleobase-related precise molecular medicine.

Graphene-wrapped MnCO_(3)/Mn_(3)O_(4) nanocomposite as an advanced anode material for lithium-ion batteries: Synergistic effect and electrochemical performances

Developing new electrode materials with a high specific capacity for excellent lithium-ion storage properties is very desirable.The MnCO_(3)/Mn_(3)O_(4)nanoparticles with uniform size(about 50 nm)and shape which are wrapped with graphene have been successfully synthesized via the one-step method for anode material of lithium-ion batteries.The as-prepared graphene-wrapped MnCO_(3)/Mn_(3)O_(4)nanocomposite exhibits remarkable electrochemical performance,including high reversible specific capacity,outstanding cycling stability,and excellent rate capability in comparison with the bare MnCO_(3)and MnCO_(3)/Mn_(3)O_(4)nanocomposite.This is because the synergistic effect of MnCO_(3)and Mn_(3)O_(4)nanoparticles and graphene nanosheets act as both electron conductors and volume buffer layers.From the scanning electron microscopy(SEM)analysis,we confirmed that the morphology and structure of the composite are preserved after 200 cycles.This further confirms that graphene-wrapped MnCO_(3)/Mn_(3)O_(4)nanocomposite acts as a stable template for reversible lithium-ion intercalation/deintercalation.

Engineered nanoparticles circumvent the adaptive treatment tolerance to immune-checkpoint blockade therapy

The fight against cancer has witnessed the rapid develop・ment of various therapeutic methodologies,including chemotherapy,surgery,radiotherapy,phototherapy,and the emerging immunotherapy[1].However,malignancies evolve adaptive tolerance under the threatening conditions upon therapies because of some potential biological or genetic mutations,which may cause serious adverse events,compromised therapeutic efficacy and even treatment failure.For instance,following the standard chemotherapy with paclitaxel,primary breast cancer can release exosomes that facilitate the seeding and growth of metastatic cancer cells in distant organs[2].Therefore,the term"adaptive treatment tolerance"(ATT),rather than"drug resistance",has been employed to better describe the dynamic evolution of this phenomenon during/post cancer therapy.