Molecular Engineering of Bright NIR-I/NIR-II Nanofluorophores for High-Resolution Bioimaging and Tumor Detection in Vivo.

A comprehensive approach for the construction of NIR-I/NIR-II nanofluorophores with exceptional brightness and excellent chemo- and photostability has been developed. This study first confirmed that the amphiphilic molecules with stronger hydrophobic moieties and weaker hydrophilic moieties are superior candidates for constructing brighter nanofluorophores, which are attributed to its higher efficiency in suppressing the intramolecular charge transfer/aggregation-caused fluorescence quenching of donor-acceptor-donor type fluorophores. The prepared nanofluorophore demonstrates a fluorescence quantum yield exceeding 4.5% in aqueous solution and exhibits a strong NIR-II tail emission up to 1300 nm. The superior performance of the nanofluorophore enabled the achievement of high-resolution whole-body vessel imaging and brain vessel imaging, as well as high-contrast fluorescence imaging of the lymphatic system in vivo. Furthermore, their potential for highly sensitive fluorescence detection of tiny tumors in vivo has been successfully confirmed, thus supporting their future applications in precise fluorescence imaging-guided surgery in the early stages of cancer.

A portable CRISPR-Cas12a triggered photothermal biosensor for sensitive and visual detection of Staphylococcus aureus and Listeria monocytogenes.

The detection of foodborne pathogens is crucial for ensuring the maintenance of food safety. In the present study, a portable CRISPR-Cas12a triggered photothermal biosensor integrating branch hybrid chain reaction (bHCR) and DNA metallization strategy for sensitive and visual detection of foodborne pathogens was proposed. The sheared probes were utilized to block the locker probes, which enabled preventing the assembly of bHCR in the absence of target bacteria, while target bacteria can activate the cleavage of sheared probes through CRISPR-Cas12a. Therefore, the locker probes functioned as initiating chains, triggering the formation of the branching double-stranded DNA consisting of H1, H2, and H3. The silver particles, which were in situ deposited on the DNA structure, functioned as a signal factor for conducting photothermal detection. Staphylococcus aureus and Listeria monocytogenes were selected as the foodborne pathogens to verify the analytical performance of this CRISPR-Cas12a triggered photothermal sensor platform. The sensor exhibited a sensitive detection with a low detection limit of 1 CFU/mL, while the concentration ranged from 100 to 108 CFU/mL. Furthermore, this method could efficiently detect target bacteria in multiple food samples. The findings demonstrate that this strategy can serve as a valuable reference for the development of a portable platform enabling quantitative analysis, visualization, and highly sensitive detection of foodborne bacteria.

Strategies and materials for the prevention and treatment of biofilms.

Biofilms are aggregates of organized microbial growth that function as barriers and create a stable internal environment for cell survival. The bacteria in the biofilms exhibit characteristics that are quite different from the planktonic bacteria, such as strong resistance to antibiotics and other bactericides, getting out of host immunity, and developing in harsh environments, which all contribute to the persistent and intractable treatment. Hence, there is an urgent need to develop novel materials and strategies to combat biofilms. However, most of the reviews on anti-biofilms published in recent years are based on specific fields or materials. Microorganisms are ubiquitous, except in the context of medical and health issues; however, biofilms exert detrimental effects on the advancement and progress of various fields. Therefore, this review aims to provide a comprehensive summary of effective strategies and methodologies applicable across all industries. Firstly, the process of biofilms formation was introduced to enhance our comprehension of the "enemy". Secondly, strategies to intervene in the important links of biofilms formation were discussed, taking timely action during the early weak stages of the "enemy". Thirdly, treatment strategies for mature biofilms were summarized to deal with biofilms that break through the defense line. Finally, several substances with antibacterial properties were presented. The review concludes with the standpoint of the author about potential developments of anti-biofilms strategies. This review may help researchers quickly understand the research progress and challenges in the field of anti-biofilms to design more efficient methods and strategies to combat biofilms.

Functionalized graphene-based electrochemical array sensors for the identification of distinct conformational states of Amyloid Beta in Alzheimer's disease.

Aß oligomers have been widely accepted as significant biomarkers for Alzheimer's disease (AD) detection, monitoring, and therapy since they are highly correlated with AD development. In this work, an electrochemical array-based sensing platform was successfully built using a group of functionalized graphene with different physicochemical features. Since the electro-insulated Aß peptide species severely interfered with the electron transport on the electrode surface, the presence of Aß led to a significant change in the electrochemical impedance signal. The resulting variety of the impedance was then classified and processed by linear discriminant analysis. The constructed sensing platform can discriminate different Aß forms, the mixture of various Aß forms, and different ratios of Aß42 to Aß40 with 100% accuracy by only the combination of dual probes. Furthermore, it also exhibited excellent performance for screening Aß inhibitors and metal chelators. The strategy utilizes the infinitesimal general discrepancy instead of specific biomarker recognition, exhibiting the advantage of no requirement to know the exact information about the specific ligand and receptor in advance, which is promising to be widened for the other biosensing detection fields.

Target Recognition- and HCR Amplification-Induced In Situ Electrochemical Signal Probe Synthesis Strategy for Trace ctDNA Analysis.

An electrochemical-DNA (E-DNA) sensor was constructed by using DNA metallization to produce an electrochemical signal reporter in situ and hybridization chain reaction (HCR) as signal amplification strategy. The cyclic voltammetry (CV) technique was used to characterize the electrochemical solid-state Ag/AgCl process. Moreover, the enzyme cleavage technique was introduced to reduce background signals and further improve recognition accuracy. On the basis of these techniques, the as-prepared E-DNA sensor exhibited superior sensing performance for trace ctDNA analysis with a detection range of 0.5 fM to 10 pM and a detection limit of 7 aM. The proposed E-DNA sensor also displayed excellent selectivity, satisfied repeatability and stability, and had good recovery, all of which supports its potential applications for future clinical sample analysis.

Precisely controlled and deeply penetrated micro-nano hybrid multifunctional motors with enhanced antibacterial activity against refractory biofilm infections.

The biofilm resistance of microorganisms has severe economic and environmental implications, especially the contamination of facilities associated with human life, including medical implants, air-conditioning systems, water supply systems, and food-processing equipment, resulting in the prevalence of infectious diseases. Once bacteria form biofilms, their antibiotic resistance can increase by 10-1,000-fold, posing a great challenge to the treatment of related diseases. In order to overcome the contamination of bacterial biofilm, destroying the biofilm's matrix so as to solve the penetration depth dilemma of antibacterial agents is the most effective way. Here, a magnetically controlled multifunctional micromotor was developed by using H2O2 as the fuel and MnO2 as the catalyst to treat bacterial biofilm infection. In the presence of H2O2, the as-prepared motors could be self-propelled by the generated oxygen microbubbles. Thereby, the remotely controlled motors could drill into the EPS of biofilm and disrupt them completely with the help of bubbles. Finally, the generated highly toxic •OH could efficiently kill the unprotected bacteria. This strategy combined the mechanical damage, highly toxic •OH, and precise magnetic guidance in one system, which could effectively eliminate biologically infectious fouling in microchannels within 10 min, possessing a wide range of practical application prospects especially in large scale and complex infection sites.

A DNase-mimetic artificial enzyme for the eradication of drug-resistant bacterial biofilm infections.

The construction of multifunctional nano-enzymes is a feasible strategy for fighting multi-drug resistant (MDR) bacterial biofilm-associated infections. Extracellular DNA (eDNA) is an important functional part of biofilm formation, including the initial adherence of bacteria to subsequent development and eventual maturation. A nano-enzyme platform of graphene oxide-based nitrilotriacetic acid-cerium(IV) composite (GO-NTA-Ce) against bacterial biofilm infection has been developed. When located at the site of bacteria-associated infection, GO-NTA-Ce could inhibit the biofilm formation and effectively disperse the formed biofilm by degrading the eDNA. In addition to Ce-mediated deoxyribonuclease (DNase)-like activity, near-infrared laser irradiation of GO-NTA-Ce could produce local hyperthermia to kill the bacteria that lost the protection by the biofilm matrix. In addition, graphene is also a new green broad-spectrum antimicrobial material that can exert its antimicrobial effects through physical damage and chemical damage. In short, our GO-NTA-Ce nano-enzyme platform is capable of effectively eradicating drug-resistant bacterial biofilm infections through the triple action of DNase-like enzyme properties, photothermal therapy, and graphene-based antimicrobial activity, and the nano-composite has excellent potential for the treatment of MDR bacterial biofilm infections.

Ultrabright AIEdots with tunable narrow emission for multiplexed fluorescence imaging.

AIEgen doped fluorescent nanodots (AIEdots) have attracted lots of attention, due to their superior characteristics as fluorescent probes, such as excellent photostability, large Stokes shift, high brightness and tunable emission. Unfortunately, most of the currently available AIEdots exhibit broad emission bandwidth, which limits their applications in multiplexed fluorescence imaging and detection. In this work, the strategy of designing and fabricating narrow emissive AIEdots (NE-AIEdots) with tunable wavelengths was presented by constructing a light-harvesting system with high energy transfer efficiency. Efficient intra-particle energy transfer from highly doped AIEgens, serving as the light-harvesting antenna, to the lightly doped narrow emissive fluorophore, resulted in high brightness and narrow emission. The emission band of NE-AIEdots with the full-width-at-half-maximum varied from 18 to 36 nm was 3-6.3 times narrower than that of traditional AIEdots. The single-particle brightness of NE-AIEdots was over 5-times that of commercial quantum dots under the same excitation and collection conditions. Taking advantage of the superior performance of these NE-AIEdots, multiplexed fluorescence imaging of lymph nodes in living mice was realized, which supported the future applications of NE-AIEdots for in vivo multiplexed labeling and clinical surgery.

Characterization of the early pathology of cochlear stereocilia in four inbred mouse strains with progressive hearing loss.

OBJECTIVE: Inbred strains of mice offer promising models for understanding the genetic basis of age-related hearing loss (AHL). NOD/LtJ, A/J, DBA/2J and C57BL/6J mice are classical models of age-related hearing loss and exhibit early onset of pathology of AHL. This study was carried out to characterize the early pathology of cochlear stereocilia in the four mouse strains with age-related hearing loss. METHODS: The structural features of stereocilia in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice were observed by scanning electron microscopy (SEM) at age 2, 4, 6 or 8, and 10 or 12 weeks. Meanwhile, auditory-evoked brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) amplitudes of the mice were measured at various intervals (3, 4, 6, 8, 10 and 12 weeks of age). RESULTS: The ABR thresholds in NOD/LtJ, A/J and DBA/2J mice increased with age from 3 to 12 weeks. DPOAE amplitudes in NOD/LtJ, A/J, DBA/2J mice were very low at 4 weeks and became negative at 8 weeks at f2 frequency of 17 672 Hz. In addition to the progressive hearing loss, the four mouse strains displayed early onset (at 2 weeks of age) and progressive degeneration of stereocilia in hair cells. CONCLUSION: Early degeneration of stereocilia contributes to the functional impairment of hair cells and hearing loss in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice.