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 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 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.

Remote vectorial vibration sensing based on locally stabilized Mach-Zehnder interferometers using multi-core fiber and optical phase-locking.

We report on remote sensing of vectorial vibration based on locally stabilized Mach-Zehnder interferometers (MZIs) using commercial multi-core fiber (MCF). Hexa-MZIs with a shared common reference arm are constructed by a 7-core MCF to acquire remotely vectorial vibration. A set of corresponding local receivers consisting of optical phase-locked loops (OPLLs) for not only eliminating the impact of environmental perturbations but also maintaining the stable operation and relative stability among the MZIs, allows guaranteed stabilized remote sensing. It moreover ensures a linearized phase detection, and thus an improved sensing sensitivity and dynamic range. This way, by exploiting the symmetrically geometric distribution for the cores of 7-core MCF, the proposed all-fiber design can enable highly precise remote extraction of vibration in a vectorial manner with a simplified remote structure. We achieve vectorial remote sensing for vibrations with ∼0.1076° and ∼0.3603 µm precision for the angle and displacement, respectively, over 10 km.

A study of intentional inhibition of food stimuli among female restricted eaters.

Restrictive eating is the propensity to restrict food consumption to control body weight. Most previous studies have focused on reactive inhibition induced by external cessation signals. Individuals usually engage in intentional inhibition, an internal form of inhibitory control that arises spontaneously in the absence of an explicit external inhibitory signal. However, there has been no clear research on intentional inhibition in restricted eaters. Therefore, the Go/No-Go/Choose experimental paradigm was used in this study to investigate the performance of intentional inhibition among restrained and unrestrained eaters under general stimuli, food stimuli, and food context conditions. The findings showed that only when food stimuli were present did the intentional inhibition of restricted and non-restricted eaters differ. In contrast to non-restricted eaters, restricted eaters significantly inhibit high-calorie foods in favor of low-calorie ones. There was no difference in intentional inhibition responses between the two groups in the non-food-related or food-context conditions, indicating that the intentional inhibition process was specific to restricted/non-restricted eaters.

Hypoxia deactivates epigenetic feedbacks via enzyme-derived clicking proteolysis-targeting chimeras.

Epigenetic mediation through bromodomain and extraterminal (BET) proteins have progressively translated protein imbalance into effective cancer treatment. Perturbation of druggable BET proteins through proteolysis-targeting chimeras (PROTACs) has recently contributed to the discovery of effective therapeutics. Unfortunately, precise and microenvironment-activatable BET protein degradation content with promising tumor selectivity and pharmacological suitability remains elusive. Here, we present an enzyme-derived clicking PROTACs (ENCTACs) capable of orthogonally cross-linking two disparate small-molecule warhead ligands that recognize BET bromodomain-containing protein 4 (BRD4) protein and E3 ligase within tumors only upon hypoxia-induced activation of nitroreductase enzyme. This localized formation of heterobifunctional degraders promotes specific down-regulation of BRD4, which subsequently alters expression of epigenetic targets and, therefore, allows precise modulation of hypoxic signaling in live cells, zebrafish, and living mice with solid tumors. Our activation-feedback system demonstrates compelling superiorities and may enable the PROTAC technology with more flexible practicality and druggable potency for precision medicine in the near future.

Remote Michelson interferometric phase sensor based on dual-core fiber transmission and linear phase demodulation.

We present a remote Michelson interferometric phase sensor based on dual-core fiber transmission and linear phase demodulation. The former allows for synchronous transmission of both sensing signal and reference lights, enabling efficient suppression for the environmental disturbances along the transmission link and for the incoherent phase noise between the two lights. The latter is conducted by two optical phase-locked loops, one of which consists of a fiber stretcher that is used to eliminate the residual phase noises, thus stabilizing the operation point while the other relies on a phase modulator that is used to track the remote phase changes, thus achieving a highly linearized phase demodulation. A remote phase sensing over a 20 km fiber link with less than 3% nonlinear phase error over 3π range has been readily realized, corresponding to more than 10 times extension in a linear phase demodulation range. The proposed system shows great potential in the field of remote phase sensing for a variety of physical quantities.

Recomposition and storage of sunlight with intelligent phosphors for enhanced photosynthesis.

This work presents a smart solar energy regulation strategy using photon tunable long persistent phosphors as solar energy harvesting antennas to enhance overall sunlight utilization by photosynthetic organisms in multiple modes.

Comparison of Intentional Inhibition and Reactive Inhibition in Adolescents and Adults: An ERP Study.

In contrast to reactive inhibition, intentional inhibition is the internally generated decision to "stop" without any external signals. Whether adults and adolescents' neural correlates on these two inhibitions have any differences is still unknown. We measured 20 adults and 21 adolescents' ERP-related N2 using a free-choice Go/Nogo task. The results of the adult's group showed that the mean amplitude and peak latency of intentional Nogo-N2 did not differ from the reactive Nogo-N2. In contrast, the mean amplitude and peak latency for reactive Nogo-N2 in the adolescent group was significantly greater than what was observed for the intentional Nogo-N2. Comparison across groups revealed that the mean amplitude and peak latency of reactive Nogo-N2 were significantly greater in adolescents than in adults, while intentional Nogo-N2 did not differ between groups. These findings may indicate that adolescents lack of self-control is more reflected in reactive inhibition, if adolescents decide whether to do, they will be as good as adults.

Sustained Effect of Music Training on the Enhancement of Executive Function in Preschool Children.

Musical training is an enrichment activity involving multiple senses, including auditory, visual, somatosensorial, attention, memory, and executive function (EF), all of which are related to cognition. This study examined whether musical training enhances EF in preschool children who had not undergone previous systematic music learning. This study also explored the after-effects 12 weeks after cessation of musical training. Participants were 61 preschool children from a university-affiliated kindergarten in North China. The experimental group underwent 12 weeks of integrated musical training (i.e., music theory, singing, dancing, and role-playing), while the control group performed typical daily classroom activities. The three components (inhibitory control, working memory, cognitive flexibility) of executive functions were evaluated using the Day/Night Stroop, Dimensional Change Card Sort, Dot Matrix Test, and Backward Digit Span Task. In Experiment 1, EFs were tested twice-before (T1) and after (T2) the music training. The results showed that children's EFs could be promoted by musical training. In addition, EFs were tested again 12 weeks later after the end of the intervention (T3) in Experiment 2. We discovered that integrated musical training demonstrated a sustained promotion effect.