Michelsenkramer3631

Cowpea mosaic virus (CPMV) is a potent immunogenic adjuvant and epitope display platform for the development of vaccines against cancers and infectious diseases, including coronavirus disease 2019. However, the proteinaceous CPMV nanoparticles are rapidly degraded in vivo. Multiple doses are therefore required to ensure long-lasting immunity, which is not ideal for global mass vaccination campaigns. Therefore, we formulated CPMV nanoparticles in injectable hydrogels to achieve slow particle release and prolonged immunostimulation. Liquid formulations were prepared from chitosan and glycerophosphate (GP) before homogenization with CPMV particles at room temperature. The formulations containing high-molecular-weight chitosan and 0-4.5 mg mL-1 CPMV gelled rapidly at 37 °C (5-8 min) and slowly released cyanine 5-CPMV particles in vitro and in vivo. Kenpaullone molecular weight Importantly, when a hydrogel containing CPMV displaying severe acute respiratory syndrome coronavirus 2 spike protein epitope 826 (amino acid 809-826) was administered to mice as a single subcutaneous injection, it elicited an antibody response that was sustained over 20 weeks, with an associated shift from Th1 to Th2 bias. Antibody titers were improved at later time points (weeks 16 and 20) comparing the hydrogel versus soluble vaccine candidates; furthermore, the soluble vaccine candidates retained Th1 bias. We conclude that CPMV nanoparticles can be formulated effectively in chitosan/GP hydrogels and are released as intact particles for several months with conserved immunotherapeutic efficacy. The injectable hydrogel containing epitope-labeled CPMV offers a promising single-dose vaccine platform for the prevention of future pandemics as well as a strategy to develop long-lasting plant virus-based nanomedicines.Photoactivatable or photoremovable protecting groups (PPGs) have become a powerful material and gained enormous interest in the field of biomedical applications. PPGs have been utilized for noninvasive, on-demand, spatio-temporal controlled release of biological effectors by irradiation with light to induce biochemical function. Over the past few years, o-hydroxycinnamate (oHC)-based PPGs have received considerable attention for the release of molecules of interest by either UV (one-photon) or near-IR (two-photon) irradiation. In this miniperspective, we have summarized the development of oHC PPGs for bioimaging and the controlled release of therapeutics, bioactive volatiles and other payloads with real-time monitoring. In addition, several future perspectives of oHC systems have been highlighted at the end of this miniperspective.Supramolecular polymers, originating from the interplay between polymer science and supramolecular chemistry, have attracted increasing interest in the scientific and industrial communities. To date, most supramolecular polymers are constructed in homogeneous solutions. Supramolecular polymerization normally takes place spontaneously in solutions, thus creating challenges in fabricating supramolecular polymers in a controlled manner. By combining supramolecular polymerization and interfacial polymerization, supramolecular polymerization can be transferred from homogeneous solutions to interfaces, which allows for the controlled production of supramolecular polymers. In this Perspective, we will summarize recent progress and the advantages in supramolecular polymerization at solid-liquid and liquid-liquid interfaces. Meanwhile, current challenges and opportunities in the field of supramolecular polymerization at interfaces are proposed and discussed. It is anticipated that this Perspective will inspire supramolecular polymerization at interfaces and facilitate the construction of supramolecular polymeric materials with diverse architectures and tailor-made functions.Silver nanoparticles (AgNPs) are effective antimicrobial substances that show promise in combatting multidrug resistance. The potential application and release of AgNPs into the environment may neutralize the selective advantage of antibiotic resistance. Systemic knowledge regarding the effect of NPs on the evolution of antibiotic resistance is lacking. Our results showed that bacteria slowly developed adaptive tolerance to ciprofloxacin (CIP) under cyclic CIP and silver ion (Ag+) cotreatment, and no resistance/tolerance was discernible when CIP and AgNP exposure was alternated. In contrast, rapid CIP resistance was induced under continuous selection by treatment with only CIP. To combat the effects of CIP and Ag+, bacteria developed convergent evolutionary strategies with similar adaptive mechanisms, including anaerobic respiration transitioning (to reduce oxidative stress) and stringent response (to survive harsh environments). Alternating AgNP exposure impeded evolutionary resistance by accelerating B12-dependent folate and methionine cycles, which reestablished DNA synthesis and partially offset high oxidative stress levels, in contrast with the effect of CIP-directed evolutionary pressure. Nevertheless, CIP/AgNP treatment was ineffective in attenuating virulence, and CIP/Ag+ exposure even induced the virulence-critical type III secretion system. Our results increase the basic understanding of the impacts of NPs on evolutionary biology and suggest prospective nanotechnology applications for arresting evolutionary antibiotic resistance.The massive accumulation of plastic waste has caused a serious negative impact on the human living environment. Replacing traditional petroleum-based polymers with biobased and biodegradable poly(l-lactic acid) (PLLA) is considered an effective way to solve this problem. However, it is still a great challenge to manufacture PLLA-based composites with high thermal conductivity and excellent mechanical properties via tailoring the microstructures of the blend composites. In the present work, a melt extrusion-stretching method is utilized to fabricate biodegradable PLLA/poly(butylene adipate-co-butylene terephthalate)/carbon nanofiber (PLLA/PBAT/CNF) blend composites. It is found that the incorporation of the extensional flow field induces the formation of multioriented microstructures in the composites, including the oriented PLLA molecular chains, elongated PBAT dispersed phase, and oriented CNFs, which synergistically improve the thermal conductivity and mechanical properties of the blend composites. At a CNFextended-chain lamellae, common "Shish-kebabs," and hybrid Shish-kebabs, which further enhance the thermal conductivity and heat resistance of the samples. This work reveals the effects of the orientation of the matrix molecular chains and crystallites on the thermal conductivity and mechanical properties of composites and provides a new way to prepare high-performance PLLA-based composites with high thermal conductivity, excellent mechanical properties, and high heat resistance.The diverse optical, magnetic, and electronic behaviors of most colloidal semiconductor nanocrystals emerge from materials with limited structural and elemental compositions. Conductive metal-organic frameworks (MOFs) possess rich compositions with complex architectures but remain unexplored as nanocrystals, hindering their incorporation into scalable devices. Here, we report the controllable synthesis of conductive MOF nanoparticles based on Fe(1,2,3-triazolate)2. Sizes can be tuned to as small as 5.5 nm, ensuring indefinite colloidal stability. These solution-processable MOFs can be analyzed by solution-state spectroscopy and electrochemistry and cast into conductive thin films with excellent uniformity. This unprecedented analysis of MOF materials reveals a strong size dependence in optical and electronic behaviors sensitive to the intrinsic porosity and guest-host interactions of MOFs. These results provide a radical departure from typical MOF characterization, enabling insights into physical properties otherwise impossible with bulk analogues while offering a roadmap for the future of MOF nanoparticle synthesis and device fabrication.Claudin 18.2 (CLDN18.2) is a new potential target for cancer therapy, especially for advanced gastric cancer (AGC). A molecular targeting probe is of importance for patient stratification and therapeutic guidance. Here, we explored an antibody-dependent molecular imaging strategy for specific detection and surgery guidance based on a CLDN18.2-specific antibody, 5C9. Two imaging probes, 124I-5C9 and Cy5.5-5C9, were synthesized. The specificity to CLDN18.2 being evidenced in the cellular experiments with control, the diagnostic utility was assessed by immunopositron emission tomography (immuno-PET) and fluorescence imaging using xenograft models. A near-infrared fluorescent II imaging probe FD1080-5C9 was designed to facilitate the comprehensive surgical removal of lesions. 124I-5C9 immuno-PET imaging clearly delineated subcutaneous CLDN18.2-positive tumors, with a peak uptake (maximum standardized uptake value; SUVmax) of 2.25 ± 0.30, whereas the highest values for the 124I-IgG and blocking groups were 0.70 ± 0.13 and 0.66 ± 0.12, respectively. Cy5.5-5C9 fluorescence imaging showed similar results. As proof of the diagnosis and guided surgery (DGS) concept, 124I-5C9 and FD1080-5C9 were simultaneously administered in orthotopic CLDN18.2-positive tumor models, facilitating the comprehensive resection of tumor tissue. Combined, 124I-5C9 and FD1080-5C9 are both promising DGS tools the former reveals CLDN18.2 in lesions as a PET probe, and the latter can guide surgery. These results provide a utility molecular imaging strategy for specific detection and surgery guidance based on a CLDN18.2-specific antibody both in AGC and other cancers.Screening for ″zero tolerance″ β-agonists requires broad-specificity and sensitivity methods. Herein, R-(-)-salbutamol (SAL) is chirally separated and designed as a hapten, and a monoclonal antibody (mAb) was first prepared with an IC50 of 0.27 ng/mL, which can recognize 38 β-agonists simultaneously. The broad-specificity of chiral mAb was explored by molecular simulation technology. Magnetic nanoparticles (MNPs) were then synthesized and applied as a signal tracer to develop a lateral flow immunoassay (LFIA). The limits of detection of MNPs-LFIA for SAL in swine urine and pork were 0.05 and 0.09 μg/kg, which was (2-125)-fold lower than that of the reported LFIAs. The recoveries were between 95.8 and 116.7%, with the coefficient of variation from 2.7 to 15.4%. Parallel analysis of 44 samples by commercial ELISA kits confirmed the reliability. Therefore, our work not only provides a broad-specificity and ultrasensitive method for β-agonists but also suggests that chirality is the new general theory that guided the rational hapten design.The potentially damaging action of dimethyl sulfoxide (DMSO) on phospholipid bilayers remains a matter of controversy. We have conducted a series of long-scale molecular dynamics simulations of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers at various levels of hydration in the presence of variable quantities of DMSO. These simulations provide evidence for a non-destructive dehydrating mechanism of action for DMSO on DOPC bilayers across a wide concentration range and levels of hydration. Specifically, under full- and low-hydration conditions, the bilayer underwent a minor lateral contraction, coinciding with surface dehydration in the presence of dilute DMSO solutions (XDMSO less then 0.3). At higher DMSO concentrations, this bilayer structure was retained despite a progressive deterioration of the hydration structure at the interface. A similar convergence of bilayer structural properties was observed under dehydration conditions for 0.3 less then XDMSO less then 0.7. Destabilization occurred for dehydrated bilayers in the presence of XDMSO ≥ 0.