Guoguang Chen

Molecular analyses of individual cells with high resolution, specificity, and sensitivity can not only reveal cellular heterogeneity but also provide a better understanding of diseases and accelerate drug discoveries. Single-cell endoscopy is an advanced live-cell technique that relies on a smart endoscope that allows minimally invasive probing of the interiors of individual cells. Compared with other single-cell analysis techniques, single-cell endoscopy has shown great promise in applications such as flexible single-cell manipulation, ultrasensitive sensing, and precise intracellular delivery. In this review, we aim to map out the landscape of recent advances in single-cell endoscopy techniques by focusing on both fundamental considerations and significant progress over the past decade. Specifically, we summarize the predominant live-cell endoscopes, including their fabrication and characterization. Furthermore, a series of valuable intracellular molecular sensing events, such as nucleic acids, proteins, ions, etc., are introduced with a main emphasis on how single-cell endoscopy can solve these issues and what merits single-cell endoscopy can provide. Finally, we briefly outline the remaining challenges and directions for the future development of single-cell endoscopy techniques.

Background: Over the past 40 years since the discovery of regenerating family proteins (Reg proteins), numerous studies have highlighted their biological functions in promoting cell proliferation and resisting cell apoptosis, particularly in the regeneration and repair of pancreatic islets and exocrine glands. Successively, short peptides derived from Reg3δ and Reg3α have been employed in clinical trials, showing favorable therapeutic effects in patients with type I and type II diabetes. However, continued reports have been limited, presumably attributed to the potential side effects. Methods: This review summarizes extensive research on Reg proteins over the past decade, combined with our own related studies, proposing that Reg proteins exhibit dimorphic effects. Results: The activity of Reg proteins is not as simplistic as previously perceived but shows auto-immunogenicity depending on different pathophysiological microenvironments. The immunogenicity of Reg proteins could recruit immune cells leading to an anti-tumor effect. Such functional diversity is correlated with their structural characteristics: the N-terminal region contributes to autoantigenicity, while the C-type lectin fragment near the C-terminal determines the trophic action. It should be noted that B-cell masking antigens might also reside within the C-type lectin domain. Conclusions: Reg proteins have dual functional roles under various physiological and pathological conditions. These theoretical foundations facilitate the subsequent development of diagnostic reagents and therapeutic drugs targeting Reg proteins.

In this research, a variety of novel amphetamine derivatives were synthesized and assessed for their potential as multifaceted antidepressant agents. Among these compounds, compound 11b demonstrated potent inhibitory effects on both serotonin and noradrenaline transporters (SERT/NET) and high affinity for histamine H₃ receptor (H₃R), and displayed low affinity for off-target receptors (H1, α1) and hERG channels, which can reduce the prolongation of the QT interval. Molecular docking studies offered a rational binding model of compound 11b when it forms a complex with SERT, NET, and the histamine H₃ receptor. In vivo behavioral studies, compound 11b dose-dependently reduced the immobility duration in the mouse FST and TST assays without a stimulatory effect on the locomotor activity. Furthermore, compound 11b had a favorable pharmacokinetic profile in rats. Thus, compound 11b has the potential to develop a novel class of drugs for the treatment of depression.

Precisely monitoring the alternations of biomolecules in traditional Chinese medicine-induced cells via a novel Raman fingerprint based analytical strategy.

Purpose: Nanotechnology has been widely used in antitumor research. The complex physiological environment has brought significant challenges to the field of antitumor micelles. The ideal micelles must not only have an invisible surface to extend the circulation time but must also enhance the retention of drugs and cellular internalization at the tumor. Methods: A graded response micelle ([email protected]/DOC) was designed to self-assemble by cRGD-poly(β-amino esters)-polyethylene glycol-ss-distearoyl phosphatidylethanolamine (cRGD-PBAE-PEG-ss-DSPE) loaded with docetaxel (DOC) and IR-780 iodide (IR780). The micelles were designed to allow the PEG shell to prolong the blood circulation time in the body and effectively accumulate in the tumor. Subsequently, the acidic microenvironment of the tumor could transform the PBAE to hydrophilic, thereby increasing the size of micelles and exposing cyclic Arg-Gly-Asp (cRGD) peptides to increase the retention and cellular internalization of micelles in the tumor. After tumor cells had captured micelles, the high expression of glutathione in the cells prompted the release of DOC and IR780. Subsequently, the IR780 was stimulated by an 808-nm laser to generate local heat and reactive oxygen species (ROS) to synergize with DOC to treat the tumor. Results: In vitro and in vivo experimental results suggested that [email protected]/DOC was a potential photochemical effective for the treatment of tumors with non-negligible antitumor activity and good biocompatibility. Conclusion: A dual-response pH/redox delivery system with on-demand RGD exposure was designed to achieve photochemotherapy of tumors with good biosafety and antitumor effects. Graphical Abstract:

Most wound dressings encounter a series of problems when dealing with the bacterial infection of wounds, for example, the antibacterial and antioxidant capacities, comfort, and mechanical properties are not suitable to meet clinical requirements. Here, we synthesized ε-polylysine-grafted nanocellulose (NCF-EPL) and polydopamine (PDA) nanoparticles and embedded them in genipin-cross-linked gelatin to prepare a hydrogel (NCF-EPL/GTP/PDA). In this system, the embedded NCF-EPL and PDA interact with the gelatin matrix to form a hydrogel with excellent physical properties. The hydrogel has broad-spectrum antibacterial abilities and good antioxidant performance, and it can effectively promote cell proliferation. Full-thickness MRSA-infected skin wound healing experiments clearly show that the NCF-EPL/GTP/PDA hydrogel can significantly accelerate the healing of infected wounds via killing bacteria and reducing inflammation, and secondary damage caused by adhesion during dressing use is effectively avoided. In short, the hydrogel provides a new method for overcoming the shortcomings of traditional dressings, and this approach provides further solutions for the selection of clinical dressings for healing wounds.

The simple and functional modification of the nanoparticle’s surface is used to efficiently deliver chemotherapeutic drugs for anti-cancer treatment. Here, we construct a nanocrystalline drug delivery system with doxorubicin wrapped in red blood cell membranes for the treatment of mouse breast cancer models. Compared with traditional free drug treatments, the biodegradable natural red blood cell membrane is combined with pure crystalline drugs. The nanoparticles obtained by the preparation method have superior properties, such as good stability, significantly delaying the release of drugs and enhancing the inhibitory effect on tumor cells. This study shows that the design of RBC as an outsourced drug delivery system provides a promising foundation for the continued development, clinical trials, and nanomedicine research of anti-cancer drug nanocarriers in the future.