Engineered Ovalbumin Nanoparticles for Cancer Immunotherapy

Ovalbumin (OVA) is a protein antigen that is widely used for eliciting cellular and humoral immune responses in cancer immunotherapy. As an alternative to solute OVA, engineering approach is developed herein towards protein nanoparticles (pNPs) based on reactive electrospraying. The resulting pNPs are comprised of polymerized OVA, where individual OVA molecules are chemically linked via poly(ethylene glycol) (PEG) units. Controlling the PEG/OVA ratio allows for fine‐tuning of critical physical properties, such as particle size, elasticity, and, at the molecular level, mesh size. As the PEG/OVA ratio decreased, OVA pNPs are more effectively processed by dendritic cells, resulting in higher OT‐I CD8+ cells proliferation in vitro. Moreover, pNPs with lower PEG/OVA ratios elicit enhanced lymphatic drainage in vivo and increased uptake by lymph node macrophages, dendritic cells, and B cells, while 500 nm OVA pNPs show poor draining lymph nodes delivery. In addition, pNPs with lower PEG/OVA ratios result in higher anti‐OVA antibody titers in vivo, suggesting improved humoral immune responses. Importantly, OVA pNPs result in significantly increased median survival relative to solute OVA antigen in a mouse model of B16F10‐OVA melanoma. This work demonstrates that precisely engineered OVA pNPs can improve the overall anti‐tumor response compared to solute antigen.As an alternative to solute antigens for cancer immunotherapy, protein nanoparticles (pNPs) comprised of polymerized antigen linked by poly(ethylene glycol) units are developed based on reactive electrospraying. This engineering approach allows fine tuning the physico‐chemical properties of pNPs such as particle size, elasticity, and mesh size. These properties are related to pNPs enhanced antigen‐specific immune responses and improved anti‐tumor efficacy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163384/3/adtp202000100-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163384/2/adtp202000100.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163384/1/adtp202000100_am.pd

Modeling immune-nanomaterial interactions using multiscale organoids

42 pagesUltrasmall nanomaterials have merged as promising delivery vehicles for drugs and vaccine candidates. In the context of immunity, such nanoparticles are capable of transport through lymphatics and enter lymph nodes to interact with specific immune cells. However, the interaction with antibody forming immune cells remain elusive. In my research, I studied the development and characterization of these nanomaterials followed by their evaluation using ex vivo immune technologies. Specifically, I investigated the possibility to model immune-nanomaterial interaction by engineering multiscale hydrogel-based immune organoids, using a combination of microfluidics, biomaterials, and mouse derived primary naïve immune cells.2022-08-2

Rethinking auditory affective descriptors through zero-shot emotion recognition in speech

International audienceZero-shot speech emotion recognition (SER) endows machines with the ability of sensing unseen-emotional states in speech, compared with conventional SER endeavors on supervised cases. On addressing the zero-shot SER task, auditory affective descriptors (AADs) are typically employed to transfer affective knowledge from seen- to unseen-emotional states. However, it remains unknown which types of AADs can well describe emotional states in speech during the transfer. In this regard, we define and research on three types of AADs, namely, per-emotion semantic-embedding, per-emotion manually annotated, and per-sample manually annotated AADs, through zero-shot emotion recognition in speech. This leads to a systematic design including prototype- and annotation-based zero-shot SER modules, relying on the input from per-emotion and per-sample AADs, respectively. We then perform extensive experimental comparisons between human and machines’ AADs on the French emotional speech corpus CINEMO for positive-negative (PN) and within-negative (WN) tasks. The experimental results indicate that semantic-embedding prototypes from pretrained models can outperform manually annotated emotional dimensions in zero-shot SER. The results further demonstrate that it is possible for machines to understand and describe affective information in speech better than human beings, with the help of sufficient pretrained models

A Full Lifecycle Authentication Scheme for Large-scale Smart IoT Applications

Peer reviewe

Unzipped Multiwalled Carbon Nanotube Oxide/Multiwalled Carbon Nanotube Hybrids for Polymer Reinforcement

Multiwalled carbon nanotubes (MWNTs) have been widely used as nanofillers for polymer reinforcement. However, it has been restricted by the limited available interface area of MWNTs in the polymer matrices. Oxidation unzipping of MWNTs is an effective way to solve this problem. The unzipped multiwalled carbon nanotube oxides (UMCNOs) exhibit excellent enhancement effect with low weight fractions, but agglomeration of UMCNOs at a relatively higher loading still hampered the mechanical reinforcement of polymer composites. In this paper, we interestingly found that the dispersion of UMCNOs in polymer matrices can be significantly improved with the combination of pristine MWNTs. The hybrids of MWNTs and UMCNOs (U/Ms) can be easily obtained by adding the pristine MWNTs into the UMCNOs aqueous dispersion, followed by sonication. With a π-stacking interaction, the UMCNOs were attached onto the outwalls of MWNTs. The morphologies and structure of the U/Ms were characterized by several measurements. The mechanical testing of the resultant poly­(vinyl alcohol) (PVA)-based composites demonstrated that the U/Ms can be used as ideal reinforcing fillers. Compared to PVA, the yield strength and Young’s modulus of U/M–PVA composites with a loading of 0.7 wt % of the U/Ms approached ∼145.8 MPa and 6.9 GPa, respectively, which are increases of ∼107.4% and ∼122.5%, respectively. The results of tensile tests demonstrated that the reinforcement effect of U/Ms is superior to the individual UMCNOs and MWNTs, because of the synergistic interaction of UMCNOs and MWNTs

cis-Azo-Promoted Construction of Vinylene-Linked Covalent Organic Frameworks with Exceptional Capability of Stepwise Water Harvesting

sp2-nitrogen atom holds a promising role either in promoting the construction of covalent organic frameworks (COFs) or tailoring their properties and functions. Herein, starting from 3,6-dimethylpyridazine as the linear ditopic monomer embedded with two adjacent sp2-nitrogen atoms, we successfully built up two novel vinylene-linked COFs upon Knoevenagel condensation with triformyl substituted aromatic derivatives. The finely-resolved powder X-ray diffraction (PXRD) patterns demonstrated their high crystalline structures with a hexagonal lattice in AA mode stacking along vertical direction. The resultant one-dimensional channels possess fruitful strong hydrogen-bond accepting sites arising from the decorated cis-azo units with two pair of the fully exposed lone pair electrons. In combination with their finely tailored micro-/nano-pore sizes, high surface areas and stable nonpolar vinylene linkages, as-prepared COFs enable exceptionally stepwise water harvesting from air, as shown by their water sorption isotherms consisting of successive steep water uptake steps even starting from a very low humidity (~10%), and reaching the largest water uptake capacity up to 1.26 g/g at P/PSTA = 0.95 (25 °C), representing the record values among the reported COF materials so far. Dynamic vapor sorption measurements confidently revealed the fast kinetics of such kinds of COFs, even in the cluster formation process. Water uptake and release cycling test manifested their outstanding hydrolytic stability, durability and adsorption-desorption retention ability

Role of breastfeeding on maternal and childhood cancers: An umbrella review of meta-analyses

Background: Multiple studies and meta-analyses have claimed that breastfeeding is inversely correlated with maternal and childhood cancers. These results could either be causal or confounded by shared risk factors. By conducting an umbrella review, we aimed to consolidate the relationship between breastfeeding and maternal and childhood cancers. Methods: We searched PubMed, Embase, Web of Science, Elsevier ScienceDirect, and Cochrane Library databases from inception to December 2022. Two reviewers independently extracted the data and assessed the quality of the studies using standardised forms. We considered two types of breastfeeding comparisons (“ever” vs “never” breastfeeding; and “longest” vs “shortest” duration). We estimated the pooled risk and 95% confidence interval (CI) for each meta-analysis. Results: We included seventeen meta-analyses with 55 comparisons. There was an inverse correlation between breastfeeding and childhood leukaemia (pooled risk = 0.90, 95% CI = 0.81-0.99), neuroblastoma (pooled risk = 0.81, 95% CI = 0.71-0.93), maternal ovarian cancer (pooled risk = 0.76, CI = 0.71-0.81), breast cancer (pooled risk = 0.85, 95% CI = 0.82-0.88), and oesophageal cancer (pooled risk = 0.67, 95% CI = 0.54-0.81) for “ever” vs “never” breastfeeding; and with childhood leukaemia (pooled risk = 0.94, 95% CI = 0.89-0.98), and maternal ovarian cancer (pooled risk = 0.84, 95% CI = 0.78-0.90) and breast cancer (pooled risk = 0.92, 95% CI = 0.89-0.96) for “longest” vs “shortest” breastfeeding duration. Conclusions: We found evidence that breastfeeding may reduce the risk of maternal breast cancer, ovarian cancers, and childhood leukaemia, suggesting positive implications for influencing women’s decision in breastfeeding. Registration: PROSPERO (CRD42021255608).</p

Biophysics-Guided Lead Discovery of HBV Capsid Assembly Modifiers

Hepatitis B virus (HBV) is the leading cause of chronic liver pathologies worldwide. HBV nucleocapsid, a key structural component, is formed through the self-assembly of the capsid protein units. Therefore, interfering with the self-assembly process is a promising approach for the development of novel antiviral agents. Applied to HBV, this approach has led to several classes of capsid assembly modulators (CAMs). Here, we report structurally novel CAMs with moderate activity and low toxicity, discovered through a biophysics-guided approach combining docking, molecular dynamics simulations, and a series of assays with a particular emphasis on biophysical experiments. Several of the identified compounds induce the formation of aberrant capsids and inhibit HBV DNA replication in vitro, suggesting that they possess modest capsid assembly modulation effects. The synergistic computational and experimental approaches provided key insights that facilitated the identification of compounds with promising activities. The discovery of preclinical CAMs presents opportunities for subsequent optimization efforts, thereby opening new avenues for HBV inhibition