Current respiratory vaccines face two major obstacles: limited breadth of protection and insufficient induction of mucosal immunity. Here, we present a neonatal Fc receptor (FcRn)-targeted mucosal delivery strategy integrating computational antigen design to address both challenges. Using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a model virus, we employed Epigraph to generate T cell epitope-optimized consensus sequences for the receptor-binding domain (RBD) and incorporated them into a modified human IgG1 Fc framework engineered for enhanced FcRn binding, yielding a single fusion antigen. In vitro, this antigen efficiently binds FcRn, facilitating epithelial transcytosis and prolonging mucosal retention. In vivo, it elicits robust cellular, humoral, and mucosal immune responses against SARS-CoV-2 and its major variants in both respiratory and systemic compartments, with evidence of tissue-resident memory responses. Following intranasal administration, the antigen conferred complete cross-protection against lethal challenge with representative SARS-CoV-2 and its variants. Notably, a low antigen dose of 0.2 μg in a two-dose regimen achieved full protection. Immunomics further revealed that this design induces a broader T and B cell repertoire. Collectively, this study establishes a generalizable framework that combines epitope-optimized antigen design with FcRn-mediated mucosal delivery, providing a promising strategy for broad-spectrum vaccine development against rapidly evolving respiratory viruses.

It is an ongoing and imperative need to monitor food colorants, for unsafe food is a terrifying threat to human health and economy. Here new Na-Ca-Cl-doped carbon dots (CDs) was fabricated by hydrothermal treatment of Miswak and m-phenylenediamine (mPD). The CDs were green-emitting with three distinctive emission centers, displaying a high quantum yield of 47%. The CDs were able to assess erythrosine in the triple channels based on their fluorescence quenching by erythrosine because of the inner filter effect, displaying high sensitivity and selectivity. Also, the quantitative measurement of erythrosine utilizing the CDs was realized in food samples and in living cells with admirable fluorescence stability and appealing biocompatibility, representing the first report on exploiting CDs for erythrosine sensing in living cells. Collectively, the CDs provide a simple efficient platform for erythrosine sensing in solutions, food samples, and living cells, broadening the implements of CDs as bio probes for food colorants.

The global health crisis posed by multidrug-resistant fungal infections necessitates the urgent development of innovative therapeutic strategies. This study presents the first successful synthesis of carbon dots (Md-CDs) through a one-step hydrothermal method using fermentation broth from the endophytic fungus Microdiplodia sp. WGHS5. Characterized as blue-emitting nanoparticles with positive charge and an average diameter of 7.3 nm, Md-CDs exhibited exceptional stability. Md-CDs displayed notable efficacy against both fungal pathogens and Gram-positive bacteria, alongside substantial biofilm inhibition capabilities. Crucially, Md-CDs did not induce drug resistance in Candida albicans. Mechanistic investigations revealed that Md-CDs penetrated microbial cells through electrostatic interactions, causing membrane disruption and subsequent protein leakage. Importantly, Md-CDs exhibited intrinsic nucleus-targeting ability in C. albicans, resulting in nucleic acid change and nucleus disassembly. Transcriptomic analysis uncovered that the treatment Candida albicans with Md-CDs led to: (1) systemic interference with protein synthesis through regulation of ribosome, translation, and aminoacyl-tRNA biosynthesis; (2) impairment of membrane integrity via modulation of fatty acid degradation, steroid biosynthesis, and fructose/mannose metabolism. In vivo evaluations demonstrate significant wound healing acceleration and enhanced antifungal activity in murine models with fungal infections, coupled with excellent biocompatibility in both cellular and animal systems. These findings highlight Md-CDs as a promising anti-drug-resistance candidate for an effective fungicide, representing a significant step forward in the development of CDs as a viable therapeutic option for fungal infections.

The development of new microbicidal compounds has become a top priority due to the emergence and spread of drug-resistant pathogenic microbes. In this study, blue-emitting and positively charged carbon dots (CDs), called Du-CDs, were fabricated for the first time utilizing the natural product extract of endophyte Diaporthe unshiuensis YSP3 as raw material through a one-step solvothermal method, which possessed varied functional groups including amino, carboxyl, hydroxyl, and sulfite groups. Interestingly, Du-CDs exhibited notably enhanced antimicrobial activities toward both bacteria and fungi as compared to the natural product extract of YSP3, with low minimum inhibitory concentrations. Moreover, Du-CDs significantly inhibited the formation of biofilms. Du-CDs bound with the microbial cell surface via electronic interaction or hydrophobic interaction entered the microbial cells and were distributed fully inside the cells. Du-CDs caused cell membrane damage and/or cell division cycle interruption, resulting in microbial cell death. Moreover, Du-CDs exhibited an improved antimicrobial effect and accelerated wound healing ability with good biocompatibility in the mouse model. Overall, we demonstrate that the formation of CDs from fungal natural products presents a promising and potential means to develop novel antimicrobial agents with great fluorescence, improved microbiocidal effect and wound healing capacity, and good biosafety for combating microbial infections.

The efficient identification and validation of drug targets are paramount in drug discovery and development. Excessive costs, intricate procedures, and laborious sample handling frequently encumber contemporary methodologies. In this study, we introduce an innovative approach for the expeditious screening of drug targets utilizing solid-state nanopores. These nanopores provide a label-free, ultra-sensitive, and high-resolution platform for the real-time detection of biomolecular interactions. By observing the changes in relative ion currents over time after mixing different peptides with small molecule drugs, and supplementing this with noise analysis, we can pinpoint specific regions of drug action, thereby enhancing both the speed and cost-efficiency of drug development. This research offers novel insights into drug discovery, expands current perspectives, and lays the groundwork for formulating effective therapeutic strategies across a spectrum of diseases.

As a crucial biomolecule of life, protein has diverse three-dimensional structural and functional properties, typically with various $\alpha$-helix and $\beta$-fold ratios. Its structure in living organisms provides important information for the study of normal or pathological physiological processes. And the nanopore technology, as a novel single-molecule sensor, has been used extensively in protein molecular detection and structural identification, because of its advantages such as label-free and easy operation. Here, we use solid-state nanopores to detect two kinds of structural proteins. The results show that since different proteins cause different blocking current signals when passing through solid-state nanopores, so we confirmed that solid-state nanopores enable protein characterization and the $\beta$-fold-rich proteins have more structural possibilities.

Real-time live-cell monitoring of Fe3+ and adenosine triphosphate (ATP) in mitochondria important for cellular functions and related to different diseases is highly desired, yet lack study. Herein, carbon dots, green bean (GB) carbon dots (CDs), were made from GB through easy one-step hydrothermal treatment. GB-CDs were in spherical form with a diameter of 13 +/- 3 nm, negatively charged, and green emissive. GB-CDs contained amino groups, which enabled their binding to Fe3+, resulting in their fluorescence quenching. Based on this, GB-CDs were employed to detect Fe3+ with high selectivity, showing a linear detection range of 10-70 mu M and a detection limit of 3.6 nM. Furthermore, the addition of ATP can recover the fluorescence quenching of GB-CDs by Fe3+. Therefore, the GB-CD + Fe3+ system was deployed to assay ATP with a linear detection range of 50-600 mu M and a detection limit of 60 nM, exhibiting high sensitivity and specificity. GB-CDs and GB-CDs + Fe3+ were individually harnessed to assess Fe3+ in tap water and ATP in fetal bovine serum. More importantly, GB-CDs can enter cells to localize in mitochondria for mitochondrial imaging with high biocompatibility and superior photostability. As a result, GB-CDs and GB-CD + Fe3+ system were implemented to track Fe3+ and ATP in mitochondria of A549, respectively. This study provides a potent tool to monitor Fe3+ and ATP in mitochondria, expanding the application of CDs as biosensors for biological compounds in subcellular organelles.

Developing smart drug delivery systems has become a feasible solution to overcome the challenges in cancer chemotherapeutics. In this work, porous boron carbon nitride (ZBCN) nanomaterials with flower-like structures assembled with BCN nanosheets were synthesized by using ZIF-L as a template. The rich hydroxyl groups on the BCN surfaces make it highly dispersible and stable in aqueous solutions. Additionally, ZBCN exhibits stable photoluminescence properties that can be utilized for cellular uptake and tracking of drug delivery. Furthermore, the flower-like ZBCN structure contributes to a large specific surface area of up to 340 m2 g-1 and a pore volume of 1.03 cm3 g-1; and the presence of rich macropores results in a high drug loading capacity of 116 wt% for paclitaxel. In vitro and in vivo anticancer experiments demonstrated that ZBCN exhibits excellent performance in delivering anticancer drugs, with in vivo tumor inhibition of 58%. This study presents a novel template method for preparing porous BCN nanomaterials, offering a promising platform for high-performance anticancer drug delivery.

Given the significant impact of ions on environment pollution and human health, it is urgently needed to establish effective and convenient ion detection approaches, particularly in living cells. In this paper, we con-structed multicolor N-doped-carbon dots (mPD-CDs) by facile one-step hydrothermal carbonization of m-phe-nylenediamine (mPD). mPD-CDs were successfully deployed for multicolor cellular imaging for animal cells, fungi, and bacteria in a wash-free way with high photostability and satisfactory biocompability. Moreover, mPD-CDs can be used as a fluorescent sensing probe for ultrasensitive detection of both iodide ion (I-) and typical heavy metals such as cadmium (Cd2+), copper (Cu2+), mercury (Hg2+), gadolinium (Gd3+), ferrous ion (Fe2+), Zinc (Zn2+), and ferric ion (Fe3+). This is the first report using CDs as optical sensing probe for the detection of Gd3+, and for detection of Fe3+ with fluorescence "turn on ". More significantly, with these versatile and fasci-nating properties, we applied mPD-CDs for intracellular ion detection in living cells like Hep G2 and S. cerevisiae, and zebra fish. Altogether, mPD-CDs displayed great potential for multicolor cell imaging and the multiple ion detection in vitro and in vivo, presenting a promising strategy for in-situ ultrasensitive sensing of multiple metal ions in the environment and the biological systems.

Electrophysiological studies of the interaction of polymers with bacterial pores provide a stratagem for single molecule detection. Aerolysin (AeL) nanopore is a promising emerging bacterial nanopore that has been extensively used for single nucleotide discrimination of very short oligonucleotides (<10 nt) with labeling. Due to its narrow constriction which is approximate 1.4 nm and highly charged pore lumen, AeL nanopore exhibits a high sensitivity in short peptide and DNA detection. Before forming the bacterial nanopore, aerolysin monomer was usually conversed from proaerolysin by activated with trypsin. The C-terminal peptide (CTP) part of proaerolysin was cleavage and the remaining part is defined as the aerolysin monomer. The CTP peptide is not uniformly charged with electrostatic distribution as positive-negative-neutral in neutral buffer solution. Here we investigated the structure of CTP during translocation through aerolysin nanopore under applied potential. The result based on characteristic blockages showed that the capture and translocation of the peptides are governed by the charged residues in the pore lumen and the potential applied.

In this work, we innovatively synthesized homochiral fluorescence nano molecularly imprinted polymers (D-MIP) with dual affinity (metal ion affinity and homochiral affinity) for the specific separation and detection of L-penicillamine (L-PA), which is a core-shell structure with a SiO2-covered CDs core and an imprinted layer with L-PA cavities. A switch for fluorescence response was built by chelating grafted Cu2+, what's more, the imprinted L-PA was pre immobilized by Cu2+ to form the directional imprinting with predetermined spatial structure. More importantly, the homochiral affinity of D-galactose in homochiral molecularly imprinted polymers (D-MIP) greatly enhanced the selective adsorption of L-PA, and D-MIP showed a high selectivity factor (α) of 3.45, which is 1.9 times that of the non-homochiral molecularly imprinted polymers (MIP). Meanwhile, D-MIP exhibited a high enantiomeric excess (ee) value of 56% for separation of racemic PA. Additionally, a high sensitive and selective method was established for the detection of L-PA.

The determination approaches of Fe (Ⅲ) in biological samples were developed by a novel water-soluble silicon nanoparticles (SiNPs). The SiNPs were synthesized by a facile microwave-assisted method, and simultaneously featured strong blue fluorescence (photoluminescence quantum yield: 25.2%), long lifetime (~13.29 ns) and good photo-stability. The fluorescence intensities of SiNPs were gradually quenched with Fe (Ⅲ) concentration increasing from 2.0 to 50 μmol/L. The detection limit of the established method was 0.56 μmol/L and the precision for eleven replicate detections of 20 μmol/L Fe (Ⅲ) was 3.2% (relative standard deviation, RSD). The spiked recoveries were 99.0%-104.5%. Results of the lifetime decay and cyclic voltammetry (CV) evidenced that the electron transfer was responsible for the fluorescence quenching mechanism of SiNPs and Fe (Ⅲ). Moreover, the SiNPs were successfully applied in the determination of Fe(Ⅲ) in different environmental waters and human serum. Finally, the resulting SiNPs exhibited the green fluorescence in HeLa cells as the optical probe.

Chemodynamic therapy (CDT), the ability to transform H2O2 into a highly toxic hydroxyl radical (˙OH) through a Fenton or Fenton like reaction to kill cancer cells, enables selective tumor therapy. However, the effect is seriously limited by the insufficiency of endogenous H2O2 in cancer cells. Additionally, the specific recognition of epitope imprinting plays an important role in targeting cancer cell markers. In this work, we prepared H2O2 self-supplying degradable epitope molecularly imprinted polymers (MIP) for effective CDT, employing fluorescent calcium peroxide (FCaO2) as an imaging probe and a source of H2O2, the exposed peptide in the CD47 extracellular region as the template, copper acrylate as one of the functional monomers and N,N'-bisacrylylcystamine (BAC) as a cross-linker. MIP with recognition sites can specifically target CD47-positive cancer cells to achieve fluorescence imaging. Under the reduction of glutathione (GSH), the MIP were degraded and the exposed FCaO2 reacted with water to continuously produce H2O2 in the slightly acidic environment in cancer cells. The self-supplied H2O2 produced ˙OH through a Fenton like catalytic reaction mediated by copper ions in the MIP framework, inducing cancer cell apoptosis. Therefore, the MIP nano-platform, which was capable of specific recognition of the cancer cell marker, H2O2 self-supply and controlled treatment, was successfully used for targeted CDT.

Multimodal imaging-guided accurate tumor-targeting and efficient synergistic therapy are of great importance for cancer therapy in vitro and in vivo. In this study, a biocompatible, tumor-targeted, on-demand chemo-/photothermal therapeutic nanoplatform (HIDSiGdNPs@PDA-HA) based on hollow mesoporous organic silica nanoparticles (HMONs) was used for bimodal imaging and multi-factor stepwise response for drug release and treatment. Targeted molecule hyaluronic acid (HA) promoted the endocytosis of HIDSiGdNPs@PDA-HA in HeLa cancer cells. The gatekeeper pH-/light-sensitive PDA coating was stimulated by the endogenous tumor acidic microenvironment and exogenous NIR laser to release doxorubicin (DOX). Thereafter, HMONs containing S-S bonds were reduced and degraded by endogenous glutathione (GSH), and the drug was further released rapidly to kill cancer cells. Importantly, the photothermal reagent indocyanine green (ICG) was always retained in the carrier, improving the effectiveness of photothermal therapy. The loaded Gd-doped silicon nanoparticles (SiGdNPs) combined with DOX and ICG led to multi-color fluorescence imaging in vitro and magnetic resonance imaging in vivo to realize targeted diagnosis and track drug distribution. The treatment results of tumor-bearing mice also proved the excellent synergistic therapy. It is believed that the multifunctional nanomaterials with dual mode imaging capability and targeted and controlled collaborative therapy would provide an alternative for accurate diagnosis and efficient treatment.

Early and accurate detection of breast cancer plays an important role in improving the survival rates of patients. In this work, we designed and synthesized the Gal-NAc-imprinted nanoparticles (GIPs) via boronate-affinity glycan-oriented surface imprinting strategy. Molecularly imprinted polymers (MIPs) were hybridized with fluorescent silicon nanoparticles (SiNPs) to target Tn antigens. However, the single fluorescent imaging mode is not conducive to obtaining accurate diagnosis, due to its poor tissue penetration. To resolve this obstacle, doping gadolinium (Gd) into SiNPs was adopted to emerge an extra significant magnetic resonance (MR) signal, achieving highly sensitive fluorescence imaging and magnetic resonance imaging (MRI) with high spatial resolution. GIPs had uniform particle size around 31.8 nm, and exhibited satisfactory fluorescence stability. The maximum adsorption capacity of GIPs was 1.15 μM/g with a high imprinting factor (IF) of 7.5. Confocal laser scanning microscope imaging revealed that the GIPs had excellent specific recognition ability with a low cytotoxicity. GIPs also showed an outstanding MR performance on cancer cells. Therefore, the synthesized nanoparticles had desirable performance in dual-model imaging to specifically target recognition cancer cells. It may have a tremendous potential in real biological samples.

Targeting is vital for precise positioning and efficient therapy, and integrated platforms for diagnosis and therapy have attracted more and more attention. Herein, we established dual-template molecularly imprinted polymer (MIP) coated fluorescent silicon nanoparticles (Si NPs) by using the linear peptide of the extracellular region of human epidermal growth factor receptor-2 (HER2) and adopting doxorubicin (DOX) as templates for targeted imaging and targeted therapy. Benefiting from the epitope imprinting approach, the imprinted sites generated by peptides on the MIP surface can be employed for recognizing the corresponding protein, which allowed the MIP to specifically and actively target HER2-positive breast cancer cells. Because of its ability to identify breast cancer cells, the MIP was applied for targeted fluorescence imaging by taking advantage of the excellent fluorescence properties of Si NPs, and the DOX-loaded MIP (MIP@DOX) can act as a therapeutic probe to effectively target and kill breast cancer cells. In fluorescence images, the targeting of the MIP promoted more uptake of the nanoparticles by cells than the non-imprinted polymer (NIP), so HER2-positive breast cancer cells incubated with the MIP exhibited stronger fluorescence, and there was no significant difference in fluorescence when HER2-negative cells and normal cells were respectively hatched with the MIP and NIP. Importantly, the cell viability was evaluated to demonstrate targeted accumulation and therapy of MIP@DOX for breast cancer cells. The nanoplatform for diagnosis and therapy combined the high sensitivity of fluorescence with the high selectivity of the molecular imprinting technique, which holds vital potential in targeted imaging and targeted therapy in vitro.