The role of microbiota in health and diseases is being highlighted by numerous studies since its discovery. Depending on the localized regions, microbiota can be classified into gut, oral, respiratory, and skin microbiota. The microbial communities are in symbiosis with the host, contributing to homeostasis and regulating immune function. However, microbiota dysbiosis can lead to dysregulation of bodily functions and diseases including cardiovascular diseases (CVDs), cancers, respiratory diseases, etc. In this review, we discuss the current knowledge of how microbiota links to host health or pathogenesis. We first summarize the research of microbiota in healthy conditions, including the gut-brain axis, colonization resistance and immune modulation. Then, we highlight the pathogenesis of microbiota dysbiosis in disease development and progression, primarily associated with dysregulation of community composition, modulation of host immune response, and induction of chronic inflammation. Finally, we introduce the clinical approaches that utilize microbiota for disease treatment, such as microbiota modulation and fecal microbial transplantation.

Owing to their excellent multiplexing ability, high sensitivity, and large dynamic range, immunoassays using surface-enhanced Raman scattering (SERS) as the readout signal have found prosperous applications in fields such as disease diagnosis, environmental surveillance, and food safety supervision. Various ever-increasing demands have promoted SERS-based immunoassays from the classical sandwich-type ones to those integrated with fascinating automatic platforms (e.g., test strips and microfluidic chips). As recent years have witnessed impressive progress in SERS immunoassays, we try to comprehensively cover SERS-based immunoassays from their basic working principles to specific applications. Focusing on several basic elements in SERS immunoassays, typical structures of SERS nanoprobes, productive optical spectral encoding strategies, and popular immunoassay platforms are highlighted, followed by their representative biological applications in the last 5 years. Moreover, despite the vast advances achieved to date, SERS immunoassays still suffer from some annoying shortcomings. Thus, proposals on how to improve the SERS immunoassay performance are also discussed, as well as future challenges and perspectives, aiming to give brief and valid guidelines for choosing suitable platforms according to particular applications.

There has been tremendous interest in constructing nanostructures by exploiting the unparalleled ability of DNA molecules in self-assembly. We have seen the appearance of many fantastic, "art-like" DNA nanostructures in one, two, or three dimensions during the last two decades. More recently, much attention has been directed to the use of these elegant nanoobjects for applications in a wide range of areas. Among them, diagnosis and therapy (i.e., theranostics) are of particular interest given the biological nature of DNA. One of the major barricades for the biosensor design lies in the restricted target accessibility at the solid-water interface. DNA nanotechnology provides a convenient approach to well control the biomolecule-confined surface to increase the ability of molecular recognition at the biosensing interface. For example, tetrahedral DNA nanostructures with thiol modifications can be self-assembled at the gold surface with high reproducibility. Since DNA tetrahedra are highly rigid and well-defined structures with atomic precision and versatile functionality, they provide scaffolds for anchoring of a variety of biomolecular probes (DNA, aptamers, peptides, and proteins) for biosensing. Significantly, this DNA nanostructure-based biosensing platform greatly increases target accessibility and improves the sensitivity for various types of molecular targets (DNA, RNA, proteins, and small molecules) by several orders of magnitude. In an alternative approach, DNA nanostructures provide a framework for the development of dynamic nanosensors that can function inside the cell. DNA tetrahedra are found to be facilely cell permeable and can sense and image specific molecules in cells. More importantly, these DNA nanostructures can be efficient drug delivery nanocarriers. Since they are DNA molecules by themselves, they have shown excellent cellular biocompatibility with minimal cytotoxicity. As an example, DNA tetrahedra tailored with CpG oligonucleotide drugs have shown greatly improved immunostimulatory effects that makes them a highly promising nanomedicine. By taking them together, we believe these functionalized DNA nanostructures can be a type of intelligent theranostic nanodevice for simultaneous sensing, diagnosis, and therapy inside the cell.

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