A Nitroreductase-activatable Metabolic Reporter for Covalent Labeling of Pathological Hypoxic Cells in Tumorigenesis.

Aberrant hypoxic stress will initiate a cascade of pathological consequence observed prominently in tumorigenesis. Understanding of hypoxia's role in tumorigenesis is  highly essential for developing effective therapeutics, which necessitates reliable tools to specifically distinguish hypoxic tumor cells (or tissues) and correlate their dynamics with the status of disease in complex living settings for precise theranostics. So far, disparate hypoxia-responsive probe molecules and prodrugs were designed via chemical or enzymatic reactions, yet their capability in real-time reporting pathogenesis development is often compromised due to unrestricted diffusion and less selectivity towards the environmental responsiveness. Herein we present an oxygen-insensitive nitroreductase (NTR)-activatable glycan metabolic reporter (pNB-ManNAz) capable of covalently labeling hypoxic tumor cells and tissues. Under pathophysiological hypoxic environments, the caged non-metabolizable precursor pNB-ManNAz exhibited unique responsiveness to cellular NTR, culminating in structural self-immolation and the resultant ManNAz could incorporate onto cell surface glycoproteins, thereby facilitating fluorescence labeling via bioorthogonal chemistry. This NTR-responsive metabolic reporter demonstrated broad applicability for multicellular hypoxia labeling, particularly in the dynamic monitoring of orthotopic tumorigenesis and targeted tumor phototherapy in vivo. We anticipate that this approach holds promise for investigating hypoxia-related pathological progression, offering valuable insights for accurate diagnosis and treatment.

The effects of different types of emotion words on emotion picture processing - evidence from event-related potential.

Emotional information can be seen everywhere in daily life. Research on emotional words often employs lexical decision tasks to judge the veracity of words, involving only superficial processing and not the deep processing of emotional significance. Therefore, the purpose of this study is to explore the effect of types of emotional words on the processing of emotional pictures. Participants were publicly recruited for a button-press experiment to discuss the impact of emotional words on the processing of emotional pictures from both behavioral and physiological mechanisms. The results of experiment 1 show: (a) in terms of reaction time, the processing speed for negative emotional words was slower, with longer reaction times; (b) In terms of accuracy, positive emotional words had a higher correct rate than negative emotional words. The results of experiment 2 found: (a) a significant main effect of emotional word type in the late processing stage; (b) a significant interaction between emotional word type and congruency. Previously presented emotional words affect the processing of subsequently presented emotional pictures, with differences in the processing of the four types of words, indicating a significant role of language in emotional processing.

Bacteria extracellular vesicle as nanopharmaceuticals for versatile biomedical potential.

Bacteria extracellular vesicles (BEVs), characterized as the lipid bilayer membrane-surrounded nanoparticles filled with molecular cargo from parent cells, play fundamental roles in the bacteria growth and pathogenesis, as well as facilitating essential interaction between bacteria and host systems. Notably, benefiting from their unique biological functions, BEVs hold great promise as novel nanopharmaceuticals for diverse biomedical potential, attracting significant interest from both industry and academia. Typically, BEVs are evaluated as promising drug delivery platforms, on account of their intrinsic cell-targeting capability, ease of versatile cargo engineering, and capability to penetrate physiological barriers. Moreover, attributing to considerable intrinsic immunogenicity, BEVs are able to interact with the host immune system to boost immunotherapy as the novel nanovaccine against a wide range of diseases. Towards these significant directions, in this review, we elucidate the nature of BEVs and their role in activating host immune response for a better understanding of BEV-based nanopharmaceuticals' development. Additionally, we also systematically summarize recent advances in BEVs for achieving the target delivery of genetic material, therapeutic agents, and functional materials. Furthermore, vaccination strategies using BEVs are carefully covered, illustrating their flexible therapeutic potential in combating bacterial infections, viral infections, and cancer. Finally, the current hurdles and further outlook of these BEV-based nanopharmaceuticals will also be provided.

Enzymes in Synergy: Bacteria Specific Molecular Probe for Locoregional Imaging of Urinary Tract Infection in vivo.

Uropathogenic Escherichia coli (UPECs) is a leading cause for urinary tract infections (UTI), accounting for 70-90 % of community or hospital-acquired bacterial infections owing to high recurrence, imprecision in diagnosis and management, and increasing prevalence of antibiotic resistance. Current methods for clinical UPECs detection still rely on labor-intensive urine cultures that impede rapid and accurate diagnosis for timely UTI therapeutic management. Herein, we developed a first-in-class near-infrared (NIR) UPECs fluorescent probe (NO-AH) capable of specifically targeting UPECs through its collaborative response to bacterial enzymes, enabling locoregional imaging of UTIs both in vitro and in vivo. Our NO-AH probe incorporates a dual protease activatable moiety, which first reacts with OmpT, an endopeptidase abundantly present on the outer membrane of UPECs, releasing an intermediate amino acid residue conjugated with a NIR hemicyanine fluorophore. Such liberated fragment would be subsequently recognized by aminopeptidase (APN) within the periplasm of UPECs, activating localized fluorescence for precise imaging of UTIs in complex living environments. The peculiar specificity and selectivity of NO-AH, facilitated by the collaborative action of bacterial enzymes, features a timely and accurate identification of UPECs-infected UTIs, which could overcome misdiagnosis in conventional urine tests, thus opening new avenues towards reliable UTI diagnosis and personalized antimicrobial therapy management.

Enzyme-Responsive Fluorescent Labeling Strategy for In Vivo Imaging of Gut Bacteria.

Myrosinase (Myr), as a unique ß-thioglucosidase enzyme capable of converting natural and gut bacterial metabolite glucosinolates into bioactive agents, has recently attracted a great deal of attention because of its essential functions in exerting homeostasis dynamics and promoting human health. Such nutraceutical and biomedical significance demands unique and reliable strategies for specific identification of Myr enzymes of gut bacterial origin in living systems, whereas the dearth of methods for bacterial Myr detection and visualization remains a challenging concern. Herein, we present a series of unique molecular probes for specific identification and imaging of Myr-expressing gut bacterial strains. Typically, an artificial glucosinolate with an azide group in aglycone was synthesized and sequentially linked with the probe moieties of versatile channels through simple click conjugation. Upon gut bacterial enzymatic cleavage, the as-prepared probe molecules could be converted into reactive isothiocyanate forms, which can further act as reactive electrophiles for the covalent labeling of gut bacteria, thus realizing their localized fluorescent imaging within a wide range of wavelength channels in live bacterial strains and animal models. Overall, our proposed method presents a novel technology for selective gut bacterial Myr enzyme labeling in vitro and in vivo. We envision that such a rational probe design would serve as a promising solution for chemoprevention assessment, microflora metabolic mechanistic study, and gut bacterium-mediated physiopathological exploration.