Insect Cuticle Protein Nanoassemblies without Nonspecific Immune Response for Acute Methicillin-Resistant Staphylococcus aureus Pneumonia Remission.

The emergence and proliferation of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia poses a significant global public health threat. Herein, the significant remission effect against acute MRSA pneumonia was realized through the insect cuticle protein (OfCPH-2) nanoassemblies without nonspecific immune response. The lung repair results could be attributed to the transforming of M1-type to M2-type macrophage polarization and the repression of Th17 cell differentiation in mice spleens through the intervention of OfCPH-2 nanoassemblies. These findings offer a valuable insight into the application of insect protein-based materials as effective antidrug resistant strain agents as well as a powerful strategy for acute MRSA pneumonia.

Longitudinal Multi-omic Immune Profiling Reveals Age-Related Immune Cell Dynamics in Healthy Adults.

The generation and maintenance of protective immunity is a dynamic interplay between host and environment that is impacted by age. Understanding fundamental changes in the healthy immune system that occur over a lifespan is critical in developing interventions for age-related susceptibility to infections and diseases. Here, we use multi-omic profiling (scRNA-seq, proteomics, flow cytometry) to examined human peripheral immunity in over 300 healthy adults, with 96 young and older adults followed over two years with yearly vaccination. The resulting resource includes scRNA-seq datasets of >16 million PBMCs, interrogating 71 immune cell subsets from our new Immune Health Atlas. This study allows unique insights into the composition and transcriptional state of immune cells at homeostasis, with vaccine perturbation, and across age. We find that T cells specifically accumulate age-related transcriptional changes more than other immune cells, independent from inflammation and chronic perturbation. Moreover, impaired memory B cell responses to vaccination are linked to a Th2-like state shift in older adults' memory CD4 T cells, revealing possible mechanisms of immune dysregulation during healthy human aging. This extensive resource is provided with a suite of exploration tools at https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/ to enhance data accessibility and further the understanding of immune health across age.

Synthesis and Characterization of SiO2/nGO/Fe3O4/SeQDs Nanoparticles as Potential Nanocarriers in Drug Delivery Systems.

Herein, we constructed the branch-shaped SiO2/nano GO (nGO)/Fe3O4/selenium quantum dots (QDs) (SeQDs) nanoparticles (SGF/SeQDs) embodying magnetism, fluorescence, and microwave stimulus response properties to enhance the performance of releasing drugs. The SGF/SeQDs composite was characterized by technologies including powder X-ray diffraction, transmission electron microscopy, infrared spectroscopy, etc. In the nanoparticles, the branch-shaped SiO2 provides a large specific surface area, nGO as the dielectric loss-style material promotes microwave-absorbing performance, and the Fe3O4 serves as a magnetic targeting agent and microwave absorber. Integrating nGO and Fe3O4 could further strengthen the microwave absorption of the entire composite; selenium features both fluorescence and anticancer effects. The synthesized nanoparticles as carriers exhibited a branch-like mesoporous sphere of ∼260 nm, a specific surface area of 258.57 m2 g-1, a saturation magnetization of 24.59 emu g-1, and good microwave thermal conversion performance that the temperature was elevated from 25 to 70 °C under microwave irradiation. These physical characteristics, including large pore volume (5.30 nm), high specific surface area, and fibrous morphology, are in favor of loading drugs. Meanwhile, the cumulative etoposide (VP16) loading rate of the nanoparticles reached to 21 wt % after 360 min. The noncovalent interaction between the VP16 and SGF/SeQDs was mainly the hydrogen-bonding effect during the loading process. Furthermore, the drug release rates at 180 min were up to 81.46, 61.92, and 56.84 wt % at pH 4, 5, and 7, respectively. At 25, 37, and 50 °C, the rates of drug release reach 25.40, 56.84, and 65.32 wt %, respectively. After microwave stimulation at pH 7, the rate of releasing drug increased distinctly from 56.84 to 71.74 wt % compared to that of nonmicrowave irradiation. Cytotoxicity tests manifested that the carrier had good biocompatibility. Therefore, the nanoparticles are looking forward to paving one platform for further applications in biomedicine and drug delivery systems.

pH-Modulated 1D Hierarchical Self-Assembly of a Brush-Like Poly-Para-Phenylene Homopolymer.

The controllable self-assembly of conjugated homopolymers, especially homopolymers without other segments (a prerequisite for phase separation), which can afford chances to achieve tunable optical/electronic properties, remains a great challenge due to their poor solubility and has remained rarely documented. Herein, a conjugated homopolymer (DPPP-COOH) is synthesized, which has a unique brush-like structure with a conjugated dendritic poly-para-phenylene (DPPP) backbone and alkyl-carboxyl side chains at both edges of the backbone. The introduction of carboxyl makes the brush-like homopolymer exhibit pH-modulated 1D hierarchical self-assembly behavior in dilute solution, and allows for flexible morphological regulation of the assemblies, forming some uncommon superstructures including ultralong nanowires (at pH 7), superhelices (at pH 10) and "single-wall" nanotubes (at pH 13), respectively. Furthermore, the good aqueous dispersibility and 1D feature endow the superstructures formed in a high-concentration neutral solution with high broad-spectrum antibacterial performance superior to that of many conventional 1D materials.

Identification and validation of a disulfidptosis-related genes prognostic signature in lung adenocarcinoma.

Disulfidptosis, a newly revealed form of cell death, regulated by numerous genes that has been recently identified. The exact role of disulfidptosis in lung adenocarcinoma (LUAD) still uncertain. Objective of this study was to explore potential prognostic markers among disulfidptosis genes in LUAD. By combining transcriptomic information from Gene Expression Omnibus databases and The Cancer Genome Atlas, we identified differentially expressed and prognostic disulfidptosis genes. By conducting least absolute shrinkage and selection operator with multivariate Cox regression, four disulfidptosis genes were selected to create the prognostic signature. The implementation of the signature separated the training and validation cohorts into groups with high- and low-risk. Subsequently, the model was verified by conducting an independent analysis of receiver operating characteristic (ROC) curves. Further comparisons were made between the two risk-divided groups with regards the tumor microenvironment, immune cell infiltration, immunotherapy response, and drug sensitivity. The signature was constructed using four disulfidptosis-related genes: SLC7A11, SLC3A2, NCKAP1, and GYS1. According to ROC curves, the signature was effective for predicting LUAD prognosis. In addition, the prognostic signature correlated with sensitivity to chemotherapeutic agents and the efficacy of immunotherapy in LUAD. Finally, through external validation, we showed that NCKAP1 are correlated with tumor migration, proliferation, and invasion of LUAD cells. GYS1 affects immune cell, especially M2 macrophage infiltration in the tumor microenvironment. The disulfidptosis four-gene model can reliably predict the prognosis of patients diagnosed with LUAD, thereby providing valuable information for clinical applications and immunotherapy.

Stimuli-fluorochromic smart organic materials.

Smart materials based on stimuli-fluorochromic π-conjugated solids (SFCSs) have aroused significant interest due to their versatile and exciting properties, leading to advanced applications. In this review, we highlight the recent developments in SFCS-based smart materials, expanding beyond organometallic compounds and light-responsive organic luminescent materials, with a discussion on the design strategies, exciting properties and stimuli-fluorochromic mechanisms along with their potential applications in the exciting fields of encryption, sensors, data storage, display, green printing, etc. The review comprehensively covers single-component and multi-component SFCSs as well as their stimuli-fluorochromic behaviors under external stimuli. We also provide insights into current achievements, limitations, and major challenges as well as future opportunities, aiming to inspire further investigation in this field in the near future. We expect this review to inspire more innovative research on SFCSs and their advanced applications so as to promote further development of smart materials and devices.

Controllably Self-Assembled Antibacterial Nanofibrils Based on Insect Cuticle Protein for Infectious Wound Healing.

Developing self-assembled biomedical materials based on insect proteins is highly desirable due to their advantages of green, rich, and sustainable characters as well as excellent biocompatibility, which has been rarely explored. Herein, salt-induced controllable self-assembly, antibacterial performance, and infectious wound healing performance of an insect cuticle protein (OfCPH-2) originating from the Ostrinia furnacalis larva head capsule are investigated. Interestingly, the addition of salts could trigger the formation of beaded nanofibrils with uniform diameter, whose length highly depends on the salt concentration. Surprisingly, the OfCPH-2 nanofibrils not only could form functional films with broad-spectrum antibacterial abilities but also could promote infectious wound healing. More importantly, a possible wound healing mechanism was proposed, and it is the strong abilities of OfCPH-2 nanofibrils in promoting vascular formation and antibacterial activity that facilitate the process of infectious wound healing. Our exciting findings put forward instructive thoughts for developing innovative bioinspired materials based on insect proteins for wound healing and related biomedical fields.

Molecular Mechanism of Qingzaojiufei Decoction in the Treatment of Pulmonary Fibrosis based on Network Pharmacology and Molecular Docking.

BACKGROUND: In recent years, pulmonary fibrosis (PF) has increased in incidence and prevalence. Qingzaojiufei decoction (QD) is a herbal formula that is used for the treatment of PF. OBJECTIVE: In this research, network pharmacology and molecular docking methods were used to explore the major chemical components and potential mechanisms of QD in the treatment of PF. METHODS: The principal components and corresponding protein targets of QD were used to screen on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) and high-throughput experiment-and reference-guided database (HERB), Cytoscape 3.7.2 was used to construct the drug-component-target network. PF targets were collected by GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The protein-protein interaction (PPI) network was constructed by importing compound-disease intersection targets into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape3.7.2. We further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersecting targets. In the last, we validated the core targets and active compounds by molecular docking. RESULTS: The key compounds of quercetin, (-)-epigallocatechin-3-gallate, and kaempferol of QD were obtained. The key targets of AKT1, TNF, and IL6 of QD were obtained. The molecular docking results show that quercetin, (-)-epigallocatechin-3-gallate and kaempferol work well with AKT1, TNF and IL6. CONCLUSION: This research shows the multiple active components and molecular mechanism of QD in the treatment of PF and offers resources and suggestions for future studies.

A comprehensive platform for analyzing longitudinal multi-omics data.

Longitudinal bulk and single-cell omics data is increasingly generated for biological and clinical research but is challenging to analyze due to its many intrinsic types of variations. We present PALMO ( https://github.com/aifimmunology/PALMO ), a platform that contains five analytical modules to examine longitudinal bulk and single-cell multi-omics data from multiple perspectives, including decomposition of sources of variations within the data, collection of stable or variable features across timepoints and participants, identification of up- or down-regulated markers across timepoints of individual participants, and investigation on samples of same participants for possible outlier events. We have tested PALMO performance on a complex longitudinal multi-omics dataset of five data modalities on the same samples and six external datasets of diverse background. Both PALMO and our longitudinal multi-omics dataset can be valuable resources to the scientific community.

Pleiotropic effects of a mitochondrion-targeted glutathione reductase inhibitor on restraining tumor cells.

Mitochondria has been identified as a target for tumor therapy. Agents preferentially concentrated in mitochondria may exert more potent antitumor effects by interfering with the normal function of mitochondria. Glutathione reductase (GR) in mitochondria is a crucial antioxidant enzyme to maintain mitochondrial function, and has been recognized as an important target for the development of anticancer drugs. Herein, we present a triphenylphosphonium-modified anticancer agent, MT-1, which can preferentially accumulate in mitochondria and bind to GR by covalent binding manner. As a result, morphology and function of mitochondria were severely damaged, as well as cellular energy supply was severely impeded due to the simultaneously inhibition against mitochondrial respiration and glycolysis. Moreover, MT-1 was found to bind to a completely new site of GR (C278) that has never considered as binding site of inhibitors before. This new binding mode led to the change of GR structure, which affected the stability of the transition state of the catalytic process, and finally led to the inhibition of GR activity. Thus, current study provided a potentially novel tumor therapeutic strategy by targeting novel sites of GR in mitochondrion.

Coassembly of a New Insect Cuticular Protein and Chitosan via Liquid-Liquid Phase Separation.

Insect cuticle is a fiber-reinforced composite material that consists of polysaccharide chitin fibers and a protein matrix. The molecular interactions between insect cuticle proteins and chitin that govern the assembly and evolution of cuticles are still not well understood. Herein, we report that Ostrinia furnacalis cuticular protein hypothetical-1 (OfCPH-1), a newly discovered and most abundant cuticular protein from Asian corn borer O. furnacalis, can form coacervates in the presence of chitosan. The OfCPH-1-chitosan coacervate microdroplets are initially liquid-like but become gel-like with increasing time or salt concentration. The liquid-to-gel transition is driven by hydrogen-bonding interactions, during which an induced ß-sheet structure of OfCPH-1 is observed. Given the abundance of OfCPH-1 in the cuticle of O. furnacalis, this liquid-liquid phase separation process and its aging behavior could play critical roles in the formation of the cuticle.

Research advances in integrated theranostic probes for tumor fluorescence visualization and treatment.

At present, cancer is obviously a major threat to human health worldwide. Accurate diagnosis and treatment are in great demand and have become an effective method to alleviate the development of cancer and improve the survival rate of patients. A large number of theranostic probes that combine diagnosis and treatment methods have been developed as promising tools for tumor precision medicine. Among them, fluorescent theranostic probes have developed rapidly in the frontier research field of precision medicine with their real time, low toxicity, and high-resolution merit. Therefore, this review focuses on recent advances in the development of fluorescent theranostic probes, as well as their applications for cancer diagnosis and treatment. Initially, small-molecule fluorescent theranostic probes mainly including tumor microenvironment-responsive fluorescent prodrugs and phototherapeutic probes were introduced. Subsequently, nanocomposite probes are expounded based on four types of nano-fluorescent particles combining different therapies (chemotherapy, photothermal therapy, photodynamic therapy, gene therapy, etc.). Then, the capsule-type "all in one" probes, which occupy an important position in theranostic probes, are summarized according to the surface carrier type. This review aims to present a comprehensive guide for researchers in the field of tumor-related theranostic probe design and development.

Green Grinding-Coassembly Engineering toward Intrinsically Luminescent Tetracene in Cocrystals.

Developing an effective and green method toward organic functional cocrystals based on the solubility-mismatched coformers is highly desirable and very important. Herein, we applied a green two-step liquid-assisted-grinding coassembly (LAGC) in fabricating tetracene-octafluoronaphthalene (TC-OFN) cocrystals from solubility-mismatched pairs of tetracene (TC, poorly soluble, 0.2 mg mL-1) and octafluoronaphthalene (OFN, highly soluble, 0.2 × 104 mg mL-1). Such cocrystals are extremely difficult to prepare through the common solution-processing strategies. More importantly, this two-step LAGC process could allow us to efficiently prepare TC-OFN cocrystals in gram scale. The as-prepared cocrystals displayed the intrinsic green emission of TC with much higher photoluminescence quantum yield (13.75%) comparing with the pure solid TC with the almost-quenched emission (0.41%, aggregation-caused quenching (ACQ)). The ultrafast spectra study on these cocrystals verifies the successful barrier function of OFN molecules in interrupting the well-known singlet fission (SF) in TC solids. Furthermore, this method can allow us to easily fabricate fluorescent TC-OFN water inks, which can be employed to prepare luminescent paintings or highly emissive ultratransparent/flexible films.

A ZIF-90 nanoplatform loaded with an enzyme-responsive organic small-molecule probe for imaging the hypoxia status of tumor cells.

Hypoxia is one of the most common and important features occurring across a wide variety of malignancies, which can have adverse effects on the therapeutic outcomes of chemotherapy and radiotherapy. Therefore, the characterization of tumor hypoxia is of great importance in clinical tumor treatment. Herein, we firstly develop a new spectroscopic off-on probe with high sensitivity (detection limit: 5.8 ng mL-1) and good selectivity for fluorescence imaging the hypoxic status of tumor cells via its enzymatic reaction with nitroreductase in vitro and in vivo in the presence of dimethyl sulfoxide (DMSO) as a co-solvent. Inspired by the recent investigations on metal-organic frameworks (MOFs), a dual pH and ATP-responsive ZIF-90 nanoplatform was synthesized, and then PEG was post-modified through a Schiff base reaction. This allows the platform to serve as a carrier to load the hypoxia-responsive probe to investigate its response to enzyme in cells and in mice without using dimethyl sulfoxide as a co-solvent. Consequently, the two probes we synthesized here can successfully respond to nitroreductase for turn-on fluorescence imaging at a cellular level and in tumor-bearing mice. This is the first time that an enzyme-responsive organic small-molecule probe has been mounted on one of the MOFs. Our results open up a promising way for the design and application of both enzyme-responsive probes and MOFs.

Tunable low-dimensional self-assembly of H-shaped bichromophoric perylenediimide Gemini in solution.

A material with diverse self-assembled morphologies is extremely important and highly desirable because such samples can provide tunable optical and electronic properties, which are critical in applications such as organic photovoltaics, microelectronics and bio-imaging. Moreover, the synthesis and controllable self-assembly of H-shaped bichromophoric perylenediimides (PDIs) are needed to advance these materials in organic photovoltaics, microelectronics and bio-imaging; however, this has remained a great challenge thus far. Here, we successfully synthesize a novel H-shaped bichromophoric PDI Gemini through the palladium-catalyzed coupling reaction. The as-prepared PDI Gemini exhibited unprecedented tunable self-assembly behavior in solution, yielding diverse low-dimensional superstructures, such as one-dimensional (1D) helices, two-dimensional (2D) rectangular nanocrystals, pyramid-shaped parallelograms, ultralarge micro-sheets, and uniform nanospheres, under different self-assembly conditions. Of particular interest, the 2D hierarchical superstructures along with their formation mechanisms represent the first finding in the self-assembly of PDI-based molecules. This study opens a new avenue for tunable self-assembly of conjugated molecules and affords opportunities for the fabrication of novel self-assembled optical and electronic materials based on PDI molecules.

Perylene Diimide Oligomer Nanoparticles with Ultrahigh Photothermal Conversion Efficiency for Cancer Theranostics.

Developing one agent that has reasonable stability and ultrahigh photothermal conversion efficiency (PTCE) for near-infrared (NIR) photothermal cancer treatment remains a great challenge, but is highly desirable. In this research, we developed a perylene diimide (PDI)-based oligomer (OPDI) through coupling monomeric PDI derivatives together. OPDI exhibited slightly red-shifted absorption at NIR region compared with monomeric PDI. More importantly, the self-assembled OPDI nanoparticles not only exhibited high stability and preferable biocompatibility, but also possessed an ultrahigh PTCE (up to 79.8%, higher than many other photothermal agents reported before). This OPDI photothermal agent has been demonstrated to exhibit excellent therapeutic effects. Our research provides a guide for the exploitation of photothermal agents with ultrahigh PTCE.

Internal standard fluorogenic probe based on vibration-induced emission for visualizing PTP1B in living cells.

Herein, as a proof of concept, we developed the first enzymatic VIE fluorogenic probe for protein tyrosine phosphatase 1B (PTP1B). The detection and imaging of PTP1B using VIE in living cells were both realized. Particularly importantly, the designed probe herein provides a guideline and platform for the development of new VIE-based enzymatic probes.

Reducing aggregation caused quenching effect through co-assembly of PAH chromophores and molecular barriers.

The features of well-conjugated and planar aromatic structures make π-conjugated luminescent materials suffer from aggregation caused quenching (ACQ) effect when used in solid or aggregated states, which greatly impedes their applications in optoelectronic devices and biological applications. Herein, we reduce the ACQ effect by demonstrating a facile and low cost method to co-assemble polycyclic aromatic hydrocarbon (PAH) chromophores and octafluoronaphthalene together. Significantly, the solid photoluminescence quantum yield (PLQYs) for the as-resulted four micro/nanococrystals are enhanced by 254%, 235%, 474 and 582%, respectively. Protection from hydrophilic polymer chains (P123 (PEO20-PPO70-PEO20)) endows the cocrystals with superb dispersibility in water. More importantly, profiting from the above-mentioned highly improved properties, nano-cocrystals present good biocompatibility and considerable cell imaging performance. This research provides a simple method to enhance the emission, biocompatibility and cellular permeability of common chromophores, which may open more avenues for the applications of originally non- or poor fluorescent PAHs.

A novel non-enzymatic hydrolytic probe for dipeptidyl peptidase IV specific recognition and imaging.

A novel non-enzymatic hydrolytic probe for DPP IV is obtained. And this new probe can be used for special DPP IV recognition and imaging in living cells. Importantly, one general strategy for the construction of new non-enzymatic fluorescent probes for many important proteases can be proposed based on the present study.