Nonlinear optical endomicroscopy for label-free functional histology in vivo

This manuscript reports on the first two-photon,label-free,metabolic imaging of biological tissues in vivo at histological resolution on an extremely compact,fiber-optic endomicroscopy platform.This system provides new opportunities for performing noninvasive and functional histological imaging of internal organs in vivo,in situ and in real time.As a routine clinical procedure,traditional histology has made significant impacts on medicine.However,the procedure is invasive and time consuming,suffers random sampling errors,and cannot provide in vivo functional information.The technology reported here features an extremely compact and flexible fiber-optic probe~2 mm in diameter,enabling direct access to internal organs.Unprecedented two-photon imaging quality comparable to a large bench-top laser scanning microscope was achieved through technological innovations in double-clad fiber optics and miniature objective lenses(among many others).In addition to real-time label-free visualization of biological tissues in situ with subcellular histological detail,we demonstrated for the first time in vivo two-photon endomicroscopic metabolic imaging on a functioning mouse kidney model.Such breakthroughs in nonlinear endoscopic imaging capability present numerous promising opportunities for paradigm-shifting applications in both clinical diagnosis and basic research.

Gut Microbiota Brings a Novel Way to Illuminate Mechanisms of Natural Products in vivo

Poor bioavailability and undefined major/direct targets are two major obstacles for herbal medicines and natural products（NPs） to elucidate their precise mechanisms in vivo. Gut microbiota is an important bridge between eukayotic body and environment, which can interact with a majority of medicines with poor bioavailability and mediate their in vivo pharmacological activities. There are two main modes through which gut microbiota may mediate the pharmacological effects of NPs. First, gut microbiota catabolizes the NPs in herbal medicines into secondary metabolites with higher bioavialability and/or higher activity, facilitating the NPs enter circulation and exert beneficial impact at the pathological spot. Second, herbal medicines and NPs can favorably shift the compositional structure of gut microbiota, thereby performing remote functions to diseased organs/tissues via the systemic impaction of gut microbiota. In this review, the potential pathways were summarized through which gut microbes facilitate the pharmacological functions of herbal medicines and NPs and highlight the significance of gut microbiota in clarifying the in vivo mechanisms of herbal medicines and NPs.