PEI-Based Nanoparticles for Tumor Immunotherapy via In Situ Antigen-Capture Triggered by Photothermal Therapy

Activating a tumor antigen-specific immune response is key to the success of tumor immunotherapy and the development of personalized antitumor therapy. Nanocarriers can capture, enrich, and protect in situ produced tumor antigens due to immunogenic cell death (ICD), thus enhancing the tumor-specific immune response. Developing multifunctional nanocarriers that combine multiple antigen capturing mechanisms is crucial to the activation of tumor-specific immune responses. In this study, polyethylenimine (PEI) was employed as a main building block to construct a series of multifunctional indocyanine green (ICG)-loaded nanoparticles to capture antigens via multiple mechanisms: electrostatic interactions with PEI, hydrophobic interactions with the thermosensitive segment (POEGMA300), and covalent bonding with the pyridyl disulfide (PDS) groups, respectively. Their capacity of ICD induction, tumor antigen-capture, and antitumor immune responses were evaluated. Both the intrinsic toxicity of PEI and the ICG-mediated photothermal effect were responsible for inducing ICD. The positively charged PEI segment exhibited the best antigen-capturing ability via electrostatic interactions, promoted bone marrow-derived dendritic cell maturation and CD8+ T cell proliferation, and elicited antitumor immune responses in vivo. PDS groups bonded antigens covalently and significantly contributed to the suppression of distant tumor growth. Although the thermosensitive hydrophobic polymer segment did not contribute positively to antigen capture or tumor growth inhibition, NPs containing all of the functional modules prolonged the survival of tumor-bearing mice more than other treatments. This study provides more chemical insights into the design of polymer-based in situ nanovaccines against cancer

Preparation of Protein-like Silver–Cysteine Hybrid Nanowires and Application in Ultrasensitive Immunoassay of Cancer Biomarker

Novel protein-like silver–cysteine hybrid nanowires (<i>p</i>-SCNWs) have been synthesized by a green, simple, nontemplate, seedless, and one-step aqueous-phase approach. AgNO₃ and l-cysteine were dissolved in distilled water, forming Ag–cysteine precipitates and HNO₃. Under vigorous stirring, the pH of the solution was rapidly adjusted to 9.0 by addition of concentrated sodium hydroxide solution, leading to quick dissolution of the Ag-cysteine precipitates and sudden appearance of white precipitates of <i>p</i>-SCNWs. The <i>p</i>-SCNWs are monodispersed nanowires with diameter of 100 nm and length of tens of micrometers, and have abundant carboxyl (−COOH) and amine (−NH₂) groups at their surfaces, large amounts of peptide-linkages and S-bonding silver ions (Ag⁺) inside, making them look and act like Ag-hybrid protein nanostructures. The abundant −COOH and −NH₂ groups at the surfaces of <i>p</i>-SCNWs have been found to facilitate the reactions between the <i>p</i>-SCNWs and proteins including antibodies. Furthermore, the fact that the <i>p</i>-SCNWs contain large amounts of silver ions enables biofunctionalized <i>p</i>-SCNWs to be excellent signal amplifying chemiluminescence labels for ultrasensitive and highly selective detection of important antigens, such as cancer biomarkers. In this work, the immunoassay of carcinoembryonic antigen (CEA) in human serum was taken as an example to demonstrate the immunoassay applications of antibody-functionalized <i>p</i>-SCNWs. By the novel <i>p</i>-SCNW labels, CEA can be detected in the linear range from 5 to 400 fg/mL with a limit of detection (LOD) of 2.2 fg/mL (at signal-to-noise ratio of 3), which is much lower than that obtained by commercially available enzyme-linked immunosorbent assay (ELISA). Therefore, the synthesized <i>p</i>-SCNWs are envisioned to be an excellent carrier for proteins and related immunoassay strategy would have promising applications in ultrasensitive clinical screening of cancer biomarkers for early diagnostics of cancers

A Feasible Post-Treatment of Drying and Rewetting for Preparation of High-Flux Pluronic F127/Polyethersulfone Nanofiltration Membranes

Pluronic F127/polyethersulfone (PES) blend nanofiltration membranes were fabricated by varying polymer weight ratios of WF127/WPES in casting solutions from 0.0 to 100.0 wt %. The initial wet membranes prepared via the phase inversion method were post-treated by drying at room temperature and then immersion into water for rewetting to obtain Pluronic F127/PES nanofiltration membranes. Membrane shrinkage and swelling, cross section and surface morphologies, water uptake, surface hydrophilicity, X-ray diffraction pattern, water flux, and rejection of dyes for Pluronic F127/PES nanofiltration membranes were investigated. The introduction of Pluronic F127 into PES membranes can substantially alleviate the membrane shrinkage during drying treatment. All of the prepared Pluronic F127/PES nanofiltration membranes can completely reject Alcian blue with a molecular weight of 1299. The water permeance of Pluronic F127/PES nanofiltration membrane at WF127/WPES of 80% is as high as 176.2 L/(m2 h MPa). After long-term immersion into sodium hypochlorite solution, Pluronic F127/PES nanofiltration membranes still keep over 95.7% rejection of Alcian blue

Additional file 1 of Bilibili, TikTok, and YouTube as sources of information on gastric cancer: assessment and analysis of the content and quality

Additional file 1: Table S1. The comparison of Bilibili, TikTok, YouTube

DataSheet_1_Dynamic radiomics for predicting the efficacy of antiangiogenic therapy in colorectal liver metastases.pdf

Background and objectiveFor patients with advanced colorectal liver metastases (CRLMs) receiving first-line anti-angiogenic therapy, an accurate, rapid and noninvasive indicator is urgently needed to predict its efficacy. In previous studies, dynamic radiomics predicted more accurately than conventional radiomics. Therefore, it is necessary to establish a dynamic radiomics efficacy prediction model for antiangiogenic therapy to provide more accurate guidance for clinical diagnosis and treatment decisions.MethodsIn this study, we use dynamic radiomics feature extraction method that extracts static features using tomographic images of different sequences of the same patient and then quantifies them into new dynamic features for the prediction of treatmentefficacy. In this retrospective study, we collected 76 patients who were diagnosed with unresectable CRLM between June 2016 and June 2021 in the First Hospital of China Medical University. All patients received standard treatment regimen of bevacizumab combined with chemotherapy in the first-line treatment, and contrast-enhanced abdominal CT (CECT) scans were performed before treatment. Patients with multiple primary lesions as well as missing clinical or imaging information were excluded. Area Under Curve (AUC) and accuracy were used to evaluate model performance. Regions of interest (ROIs) were independently delineated by two radiologists to extract radiomics features. Three machine learning algorithms were used to construct two scores based on the best response and progression-free survival (PFS).ResultsFor the task that predict the best response patients will achieve after treatment, by using ROC curve analysis, it can be seen that the relative change rate (RCR) feature performed best among all features and best in linear discriminantanalysis (AUC: 0.945 and accuracy: 0.855). In terms of predicting PFS, the Kaplan–Meier plots suggested that the score constructed using the RCR features could significantly distinguish patients with good response from those with poor response (Two-sided PConclusionsThis study demonstrates that the application of dynamic radiomics features can better predict the efficacy of CRLM patients receiving antiangiogenic therapy compared with conventional radiomics features. It allows patients to have a more accurate assessment of the effect of medical treatment before receiving treatment, and this assessment method is noninvasive, rapid, and less expensive. Dynamic radiomics model provides stronger guidance for the selection of treatment options and precision medicine.</p

pH-Switched Near-Infrared Fluorescent Strategy for Ratiometric Detection of ONOO^– in Lysosomes and Precise Imaging of Oxidative Stress in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is well-known as a kind of autoimmune disease, which brings unbearable pain to the patients by multiple organ complications besides arthritis. To date, RA can be hardly cured, but early diagnosis and standard treatment can relieve symptoms and pain. Therefore, an effective tool to assist the early diagnosis of RA deserves considerable attention. On account of the overexpressed ONOO– during the early stage of RA, a near-infrared (NIR) receptor, Lyso-Cy, is proposed in this work by linker chemistry to expand the conjugated rhodamine framework by cyanine groups. Contributed by the pH-sensitive spiral ring in rhodamine, receptor Lyso-Cy has been found to be workable in lysosomes specifically, which was confirmed by the pH-dependent spectra with a narrow responding region and a well-calculated pKa value of 5.81. We presented an excellent ratiometric sensing protocol for ONOO– in an acidic environment, which was also available for targeting ONOO– in lysosomes selectively. This innovative dual-targeting responsive design is expected to be promising for assisting RA diagnosis at an early stage with respect to the joint inflammatory model established in this work at the organism level

Image_1_Circulating Metabolomic Signature in Generalized Pustular Psoriasis Blunts Monocyte Hyperinflammation by Triggering Amino Acid Response.tif

Generalized pustular psoriasis (GPP), the most grievous variant of psoriasis, is featured by dysregulated systemic inflammatory response. The cellular and molecular basis of GPP is poorly understood. Blood monocytes are key players of host defense and producers of inflammatory cytokines including IL-1β. How the immune response of monocytes is affected by metabolic internal environment in GPP remains unclear. Here, we performed a metabolomic and functional investigation of GPP serum and monocytes. We demonstrated a significant increase in IL-1β production from GPP monocytes. In GPP circulation, serum amyloid A (SAA), an acute-phase reactant, was dramatically increased, which induced the release of IL-1β from monocytes in a NLRP3-dependent manner. Using metabolomic analysis, we showed that GPP serum exhibited an amino acid starvation signature, with glycine, histidine, asparagine, methionine, threonine, lysine, valine, isoleucine, tryptophan, tyrosine, alanine, proline, taurine and cystathionine being markedly downregulated. In functional assay, under amino acid starvation condition, SAA-stimulated mature IL-1β secretion was suppressed. Mechanistically, at post-transcriptional level, amino acid starvation inhibited the SAA-mediated reactive oxygen species (ROS) formation and NLRP3 inflammasome activation. Moreover, the immune-modulatory effect of amino acid starvation was blocked by silencing general control nonderepressible 2 kinase (GCN2), suggesting the involvement of amino acid response (AAR) pathway. Collectively, our results suggested that decreased serum amino acids in GPP blunted the innate immune response in blood monocytes through AAR pathway, serving as a feedback mechanism preventing excessive inflammation in GPP.</p

Data_Sheet_1_Peptide Tat(48–60) YVEEL protects against necrotizing enterocolitis through inhibition of toll-like receptor 4-mediated signaling in a phosphatidylinositol 3-kinase/AKT dependent manner.pdf

Necrotizing enterocolitis (NEC) is a catastrophic disease largely occurring in preterm infants, and toll-like receptor 4 (TLR4) has been implicated in its pathogenesis. The current therapeutic strategies for NEC are, however, far from optimal. In the present study, a whey-derived antioxidative peptide conjugated with a cell-penetrating TAT [Tat (48–60) YVEEL] was prepared to endow it with enhanced cell uptake capability and bioavailability. The protective effect of Tat (48–60) YVEEL on experimental NEC was evaluated both in vitro and in vivo. Inhibition of TLR4-mediated signaling by Tat (48–60) YVEEL was assessed in FHC and IEC-6 enterocytes, neonatal rat model of NEC, and the mechanism underlying this effect was determined. Tat (48–60) YVEEL significantly inhibited TLR4-mediated expression of pro-inflammatory cytokines, p65 nuclear translocation and restored the impaired enterocyte migration in cultured enterocytes. In addition, Tat (48–60) YVEEL administration strikingly increased the survival rate, and reduced the severity of NEC in rats through inhibition of TLR4-mediated signaling. These protective effects of Tat (48–60) YVEEL occurred in a PI3K/AKT dependent manner, as administration of PI3K activator Ys49 abrogated its protective effects. Combined with liposomes, Tat (48–60) YVEEL demonstrated longer retention in the intestines that better for potential clinical applications. These data demonstrate that Tat (48–60) YVEEL protects against NEC through inhibition of TLR4-mediated signaling in a PI3K/AKT dependent manner, and offer a potential therapeutic approach to this disease.</p

sj-tif-1-dos-10.1177_15593258211064499 – Supplemental Material for Stereotactic Body Radiotherapy and Conventional Radiotherapy Induce Cytoskeleton Extension and Enlargement of Cell Morphology in Non-Small Cell Lung Cancer

Supplemental Material, sj-tif-1-dos-10.1177_15593258211064499 for Stereotactic Body Radiotherapy and Conventional Radiotherapy Induce Cytoskeleton Extension and Enlargement of Cell Morphology in Non-Small Cell Lung Cancer by Xiao Wang, Yanwei Lu, Zhiquan Qin, Haiwei Guo, Wenjuan Chen, Ting Ding, Jianming Tang and Haibo Zhang in Dose-Response</p

sj-tif-2-dos-10.1177_15593258211064499 – Supplemental Material for Stereotactic Body Radiotherapy and Conventional Radiotherapy Induce Cytoskeleton Extension and Enlargement of Cell Morphology in Non-Small Cell Lung Cancer

Supplemental Material, sj-tif-2-dos-10.1177_15593258211064499 for Stereotactic Body Radiotherapy and Conventional Radiotherapy Induce Cytoskeleton Extension and Enlargement of Cell Morphology in Non-Small Cell Lung Cancer by Xiao Wang, Yanwei Lu, Zhiquan Qin, Haiwei Guo, Wenjuan Chen, Ting Ding, Jianming Tang and Haibo Zhang in Dose-Response</p