Antibacterial protein hydrogels are receiving increasing attention in the aspect of bacteria-infected-wound healing. However, bacterial drug resistance and biofilm infections lead to hard healing of ...wounds, thus the construction of biological agents that can overcome these issues is essential. Here, a simple and universal method to construct antibiotic-free protein hydrogel with excellent biocompatibility and superior antibacterial activity against drug-resistant bacteria and biofilms was developed. The green industrial microbicide tetrakis (hydroxymethyl) phosphonium sulfate (THPS) as cross-linking agent can be quickly cross-linked with model protein bovine serum albumin (BSA) to form antibacterial hydrogel through simple mixing without any other initiators, subsequently promoting drug-resistance bacteria-infected wound healing. This simple gelatinization strategy allows at least ten different proteins to form hydrogels (e.g. BSA, human serum albumin (HSA), egg albumin, chymotrypsin, trypsin, lysozyme, transferrin, myohemoglobin, hemoglobin, and phycocyanin) under the same conditions, showing prominent universality. Furthermore, drug-resistance bacteria and biofilm could be efficiently destroyed by the representative BSA hydrogel (B-Hydrogel) with antibacterial activity, overcoming biofilm-induced bacterial resistance. The in vivo study demonstrated that the B-Hydrogel as wound dressing can promote reepithelization to accelerate the healing of methicillin-resistant staphylococcus aureus (MRSA)-infected skin wounds without inducing significant side-effect. This readily accessible antibiotic-free protein-based hydrogel not only opens an avenue to provide a facile, feasible and general gelation strategy, but also exhibits promising application in hospital and community MRSA disinfection and treatment.
Display omitted
•A simple and universal method to build antibiotic-free protein hydrogel was explored.•The obtained B-Hydrogel can eradicate drug-resistant bacteria and biofilms.•The B-Hydrogel can promote the healing of MRSA-infected skin wounds.
Selenoprotein plays a crucial role in immune cells and inflammatory regulation. However, as a protein drug that is easily denatured or degraded in the acidic environment of the stomach, efficient ...oral delivery of selenoprotein is a great challenge. Herein, we innovated an oral hydrogel microbeads-based biochemical strategy that can in situ synthesize selenoproteins, therefore bypassing the necessity and harsh conditions for oral protein delivery while effectively generating selenoproteins for therapeutic applications. The hydrogel microbeads were synthesized by coating hyaluronic acid-modified selenium nanoparticles with a protective shell of calcium alginate (SA) hydrogel. We tested this strategy in mice with inflammatory bowel disease (IBD), one of the most representative diseases related to intestinal immunity and microbiota. Our results revealed that hydrogel microbeads-mediated in situ synthesis of selenoproteins could prominently reduce proinflammatory cytokines secretion and mediate immune cells (e.g., reduce neutrophils and monocytes and increase immune regulatory T cells) to effectively relieve colitis-associated symptoms. This strategy was also able to regulate gut microbiota composition (increase probiotics abundance and suppress detrimental communities) to maintain intestinal homeostasis. Considering intestinal immunity and microbiota widely associated with cancers, infections, inflammations, etc., this in situ selenoprotein synthesis strategy might also be possibly applied to broadly tackle various diseases.
Because of the extremely complexed microenvironment of drug-resistant bacterial infection, nanomaterials with both bactericidal and immuno-modulating activities are undoubtedly the ideal modality for ...overcoming drug resistance. Herein, we precisely engineered the surface chemistry of selenium nanoparticles (SeNPs) using neutral (polyvinylpyrrolidone-PVP), anionic (letinan-LET) and cationic (chitosan-CS) surfactants. It was found that surface chemistry greatly influenced the bioactivities of functionalized SeNPs, their interactions with methicillin-resistant Staphylococcus aureus (MRSA), immune cells and metabolisms. LET-functionalized SeNPs with distinct metabolisms exhibited the best inhibitory efficacy compared to other kinds of SeNPs against MRSA through inducing robust ROS generation and damaging bacterial cell wall. Meanwhile, only LET-SeNPs could effectively activate natural kill (NK) cells, and enhance the phagocytic capability of macrophages and its killing activity against bacteria. Furthermore, in vivo studies suggested that LET-SeNPs treatment highly effectively combated MRSA infection and promoted wound healing by triggering much more mouse NK cells, CD8+ and CD4+ T lymphocytes infiltrating into the infected area at the early stage to efficiently eliminate MRSA in the mouse model. This study demonstrates that the novel functionalized SeNP with dual functions could serve as an effective antibacterial agent and could guide the development of next generation antibacterial agents.
X‐ray detectors have broad applications in medicine and industry. Although flexible lead‐free perovskite films are competitive because of their lightweight and low toxicity, they are less efficient ...due to low charge transport. Herein, we report low‐toxicity, flexible X‐ray detectors based on p‐type doped MA3Bi2I9 (MA=methylammonium) perovskite‐filled membranes (PFMs). Strong coordination between dopant 2,3,5,6‐tetrafluoro‐7,7,8,8‐tetracyanoquinodimethane (F4‐TCNQ) and MA3Bi2I9 and the establishment of charge‐transfer complex (CPX) improved the conductivity by four times. The flexible X‐ray detector achieved a high sensitivity of 2065 μC Gyair−1 cm−2 and an ultra‐low detection limit of 2.71 nGyair s−1, which is among the highest values in all environmentally friendly flexible X‐ray detectors. Importantly, the PFMs retained excellent charge transport under mechanical stress. All of those make flexible MA3Bi2I9 membranes more competitive as next‐generation X‐ray detection.
Molecular doping improves the conductivity of flexible lead‐free MA3Bi2I9 perovskite membranes by four times. Flexible X‐ray detector achieves a high sensitivity of 2065 μC Gyair−1 cm−2, an ultra‐low detection limit of 2.71 nGyair s−1, a high mechanical robustness, which demonstrate potential in next‐generation X‐ray detection.
Next-generation wearable electronics requires mechanical robustness. In addition to the previously reported eco-friendliness, low cost, and light weight of molecular perovskites, flexibility is also ...a desired merit for their practical use. Here we design a flexible X-ray detector based on a novel molecular perovskite, DABCO-CsBr3 (DABCO = N-N′-diazabicyclo2.2.2octonium), which is the missing link between metal-free molecular perovskites A(NH4)X3 (A = divalent organic ammoniums) and conventional metal halide based ABX3 (B = divalent metal cations) perovskites. DABCO-CsBr3 inherits its band nature from A(NH4)X3, while it exhibits a stronger stopping power. DABCO-CsBr3 shows potential for high-performance ionizing radiation detectors due to low dark current, low ion migration, and an efficient mobility–lifetime (μτ) product. Finally, a molecular-perovskite-based flexible X-ray detector is demonstrated on the basis of the DABCO-CsBr3/poly(vinylidene fluoride) composite, with a sensitivity of 106.7 μC Gyair –1 cm–2. This work enriches the molecular perovskite family and highlights the promise of molecular perovskites for the next-generation eco-friendly and wearable optoelectronic devices.
A sensitive immunochromatographic assay (ICA) using time-resolved fluorescence microspheres (TRFMs) coupled with an indirect-labeling mode was developed for simultaneously determining 22 kinds of ...β-lactams in milk samples. The TRFMs labeled anti-receptor monoclonal antibodies (mAbs) conjugated to penicillin-binding proteins (PBPs) as ternary TRFMs-mAb-PBPs (TMP) nanoscaffolds provide excellent solubility, brightness, and stability. Thanks to the fact that they not only fully expose the binding sites of PBPs, thereby enhancing the biological affinity of PBPs towards the target, but also generated superb fluorescence signals, the versatile TMP manifested unique possibilities as efficient probes for ICA with remarkable enhancement in sensitivity in β-lactams screening. The results showed that the standard curves of the 22 varying β-lactams displayed linearity in their respective concentration ranges (
R
2
> 0.98), with the cutoff values of 1–100 ng/mL. The constructed TMP-ICA was successfully applied to the analysis of real milk, with consistent results compared with liquid chromatography-tandem mass spectrometry (LC-MS), providing an effective method for sensing β-lactams in food matrices.
Graphical Abstract
To avoid false negative results due to the low cross-reactivity rate (CR) in rapid immunoassay, a group-specific antibody with homogeneous CR toward target compounds is needed for accuracy. In this ...study, tylosin (TYL) and tilmicosin (TM) were selected as model molecules. Firstly, two-dimensional similarity, electrostatic potential energy, spatial conformation and charge distribution of the haptens TYL-CMO, TYL-6-ACA, TYL-4-APA, TYL-CHO and DES-CMO and target compounds of TYL and TM were obtained using Gaussian 09W and Discovery Studio. The optimal hapten was DES-CMO because it is the most similar to TYL and TM. Subsequently, the mAb 14D5 cell line was obtained with IC
50
values of 1.59 and 1.72 ng/mL for TYL and TM, respectively, and a CR of 92.44%. Finally, amorphous carbon nanoparticles (ACNPs) were conjugated with mAb 14D5 to develop an accurate lateral flow immunoassay (LFA) for detection of TYL and TM by the reflectance value under natural light. The recoveries of TYL and TM ranged from 77.18 to 112.04% with coefficient of variation < 13.43%. The cut-off value in milk samples was 8 ng/mL, and the limits of detection were 11.44, 15.96, 22.29 and 25.53 μg/kg for chicken muscle, bovine muscle, porcine muscle and porcine liver samples, respectively, and the results being consistent with HPLC–UV. The results suggest that the developed LFA is accurate and potentially useful for on-site screening of TYL and TM in milk and animal tissue samples.
Graphical abstract
To overcome limitations with respect to the low sensitivity of rapid immunoassay methods due to dilution of the extract in extraction solution, ultra-sensitive antibodies are needed. The ...linker-tethering site between the target and carrier protein, the length of the spacer arm, and the atomic charge of the linker-tethering site between the target and spacer arm in haptens design play a pivotal role in the preparation of ultra-sensitive antibodies. In this study, carbendazim (CBZ), a systemic broad-spectrum fungicidal pesticide, was used as model compound. 2-Aminobenzimidazole was chosen as the common skeletal structure and reacted with different groups, such as alkanes and urine groups, to form haptens H1 (previously reported), H2 (novel), and H3 (novel), respectively. Subsequently, eight monoclonal antibodies (mAbs) were generated using these three haptens, which exhibited notable variation in sensitivity. The half maximal inhibitory concentration (IC50) value of mAb 4B11 based on hapten H3 against CBZ was 0.04 ng/mL, which was seven times better than that of mAb 5B10 (IC50 value of 0.28 ng/mL) prepared using hapten H2 and 129 times better than that of mAb 6D5 (IC50 value of 5.15 ng/mL) prepared using hapten H1. Finally, the optimal antigen–antibody combination was employed to establish a sensitive colloidal gold lateral flow immunoassay (CG-LFA) for CBZ detection in vegetables and fruits with convenient sample pretreatment. The developed CG-LFA shows promising practical utility and prospects for application due to its low limit of detection (0.10–0.18 ng/mL) and high recovery ratios (76.0%–96.1%) in six different samples.
Display omitted
•A novel hapten design strategy focuses on the link site and spacer arm length of the target compound.•An ultra-sensitive monoclonal antibody (mAb) 4B11 against carbendazim was prepared.•A sensitive colloidal gold lateral flow immunoassay in fruits and vegetables was developed.
The remote sensing of water clouds is useful for studying their spatial and temporal variations and constraining physical processes in climate and weather prediction models. However, radar-only ...detection provides inadequate information for the cloud droplet size distribution. Here, we propose a novel lookup-table method, which combines lidar (1064, 532 nm) and radar (8.6 mm) to retrieve profiles of cloud optical (backscatter coefficient and extinction coefficient) and microphysical properties (effective diameter and liquid water content). Through the iteration of the extinction-to-backscatter ratio, more continuous cloud optical characteristics can be obtained. Sensitivity analysis shows that a 10% error of the lidar constant will lead to a retrieval error of up to 30%. The algorithm performed precise capture of the ideal cloud signal at a specific height and at full height and the maximum relative error of the backscatter coefficients at 1064 nm and 532 nm were 6% and 4%, respectively. With the application of the algorithm in the two observation cases on single or multiple cloud layers, the results indicate that the microphysical properties mostly agree with the empirical radar measurements but are slightly different when larger particles cause signal changes of different extents. Consequently, the synergetic algorithm is capable of computing the cloud droplet size distribution. It provides continuous profiles of cloud optical properties and captures cloud microphysical properties well for water cloud studies.
X‐ray detectors have broad applications in medicine and industry. Although flexible lead‐free perovskite films are competitive because of their lightweight and low toxicity, they are less efficient ...due to low charge transport. Herein, we report low‐toxicity, flexible X‐ray detectors based on p‐type doped MA3Bi2I9 (MA=methylammonium) perovskite‐filled membranes (PFMs). Strong coordination between dopant 2,3,5,6‐tetrafluoro‐7,7,8,8‐tetracyanoquinodimethane (F4‐TCNQ) and MA3Bi2I9 and the establishment of charge‐transfer complex (CPX) improved the conductivity by four times. The flexible X‐ray detector achieved a high sensitivity of 2065 μC Gyair−1 cm−2 and an ultra‐low detection limit of 2.71 nGyair s−1, which is among the highest values in all environmentally friendly flexible X‐ray detectors. Importantly, the PFMs retained excellent charge transport under mechanical stress. All of those make flexible MA3Bi2I9 membranes more competitive as next‐generation X‐ray detection.
Molecular doping improves the conductivity of flexible lead‐free MA3Bi2I9 perovskite membranes by four times. Flexible X‐ray detector achieves a high sensitivity of 2065 μC Gyair−1 cm−2, an ultra‐low detection limit of 2.71 nGyair s−1, a high mechanical robustness, which demonstrate potential in next‐generation X‐ray detection.
PDF
