Quantitative Proteomic Analysis Reveals Functional Alterations of the Peripheral Immune System in Colorectal Cancer.

Colorectal cancer (CRC) is characterized by high morbidity, high mortality, and limited response to immunotherapies. The peripheral immune system is an important component of tumor immunity, and enhancements of peripheral immunity help to suppress tumor progression. However, the functional alterations of the peripheral immune system in CRC are unclear. Here, we used mass spectrometry-based quantitative proteomics to establish a protein expression atlas for the peripheral immune system in CRC, including plasma and five types of immune cells (CD4+ T cells, CD8+ T cells, monocytes, natural killer cells, and B cells). Synthesizing the results of the multidimensional analysis, we observed an enhanced inflammatory phenotype in CRC, including elevated expression of plasma inflammatory proteins, activation of the inflammatory pathway in monocytes, and increased inflammation-related ligand-receptor interactions. Notably, we observed tumor effects on peripheral T cells, including altered cell subpopulation ratios and suppression of cell function. Suppression of CD4+ T cell function is mainly mediated by high expression levels of protein tyrosine phosphatases. Among them, the expression of protein tyrosine phosphatase receptor type J (PTPRJ) gradually increased with CRC progression; knockdown of PTPRJ in vitro could promote T cell activation, thereby enhancing peripheral immunity. We also found that the combination of leucine-rich α-2 glycoprotein 1 (LRG1) and apolipoprotein A4 (APOA4) had the best predictive ability for colorectal cancer and has the potential to be a biomarker. Overall, this study provides a comprehensive understanding of the peripheral immune system in CRC. It also offers insights regarding the potential clinical utilities of these peripheral immune characteristics as diagnostic indicators and therapeutic targets.

SDS3 regulates microglial inflammation by modulating the expression of the upstream kinase ASK1 in the p38 MAPK signaling pathway.

BACKGROUND: Microglia, the main innate immune cells in the central nervous system, are key drivers of neuroinflammation, which plays a crucial role in the pathogenesis of neurodegenerative diseases. The Sin3/histone deacetylase (HDAC) complex, a highly conserved multiprotein co-repressor complex, primarily performs transcriptional repression via deacetylase activity; however, the function of SDS3, which maintains the integrity of the complex, in microglia remains unclear. METHODS: To uncover the regulatory role of the transcriptional co-repressor SDS3 in microglial inflammation, we used chromatin immunoprecipitation to identify SDS3 target genes and combined with transcriptomics and proteomics analysis to explore expression changes in cells following SDS3 knocking down. Subsequently, we validated our findings through experimental assays. RESULTS: Our analysis revealed that SDS3 modulates the expression of the upstream kinase ASK1 of the p38 MAPK pathway, thus regulating the activation of signaling pathways and ultimately influencing inflammation. CONCLUSIONS: Our findings provide important evidence of the contributions of SDS3 toward microglial inflammation and offer new insights into the regulatory mechanisms of microglial inflammatory responses.

Birinapant Reshapes the Tumor Immunopeptidome and Enhances Antigen Presentation.

Birinapant, an antagonist of the inhibitor of apoptosis proteins, upregulates MHCs in tumor cells and displays a better tumoricidal effect when used in combination with immune checkpoint inhibitors, indicating that Birinapant may affect the antigen presentation pathway; however, the mechanism remains elusive. Based on high-resolution mass spectrometry and in vitro and in vivo models, we adopted integrated genomics, proteomics, and immunopeptidomics strategies to study the mechanism underlying the regulation of tumor immunity by Birinapant from the perspective of antigen presentation. Firstly, in HT29 and MCF7 cells, Birinapant increased the number and abundance of immunopeptides and source proteins. Secondly, a greater number of cancer/testis antigen peptides with increased abundance and more neoantigens were identified following Birinapant treatment. Moreover, we demonstrate the existence and immunogenicity of a neoantigen derived from insertion/deletion mutation. Thirdly, in HT29 cell-derived xenograft models, Birinapant administration also reshaped the immunopeptidome, and the tumor exhibited better immunogenicity. These data suggest that Birinapant can reshape the tumor immunopeptidome with respect to quality and quantity, which improves the presentation of CTA peptides and neoantigens, thus enhancing the immunogenicity of tumor cells. Such changes may be vital to the effectiveness of combination therapy, which can be further transferred to the clinic or aid in the development of new immunotherapeutic strategies to improve the anti-tumor immune response.

A three-dimensional quantitative assessment on bony growth and symmetrical recovery of mandible after decompression for unicystic ameloblastoma.

Unicystic ameloblastoma (UAM) of the jaw can be effectively reduced in volume through decompression, which promotes bone regeneration and restores jaw symmetry. This study quantitatively evaluated changes in mandible volume and symmetry following decompression of mandibular UAM. This study included 17 patients who underwent surgical decompression followed by second-stage curettage for mandibular UAM. Preoperative and postoperative three-dimensional computed tomography (CT) images were collected. Bone volume and the area of cortical perforation were measured to assess bone growth during decompression. Mandibular volumetric symmetry was analyzed by calculating the volumetric ratio of the two sides of the mandible. Twelve pairs of landmarks were identified on the surface of the lesion regions, and their coordinates were used to calculate the mean asymmetry index (AI) of the mandible. Paired t-tests and the Mann-Whitney U test were used for statistical analysis, with p < 0.05 considered indicative of statistical significance. The mean duration of decompression was 9.41 ± 3.28 months. The mean bone volume increased by 8.07 ± 2.41%, and cortical perforation recovery was 71.97 ± 14.99%. The volumetric symmetry of the mandible improved significantly (p < 0.05), and a statistically significant decrease in AI was observed (p < 0.05). In conclusion, UAM decompression enhances bone growth and symmetry recovery of the mandible. The present evaluation technique is clinically useful for quantitatively assessing mandibular asymmetry.

Hydrostability, mechanical resilience, and biodegradability of paper straws fabricated through lignin-based polyurethane and chitosan binary emulsion bonding.

This study focuses on enhancing the strength and water stability of paper straws through a novel approach involving a binary emulsion of lignin-based polyurethane and chitosan. Kraft lignin serves as the raw material for synthesizing a blocked waterborne polyurethane, subsequently combined with carboxylated chitosan to form a stable binary emulsion. The resulting emulsion, exhibiting remarkable stability over at least 6 months, is applied to the base paper. Following emulsion application, the paper undergoes torrefaction at 155 °C. This process deblocks isocyanate groups, enabling their reaction with hydroxyl groups on chitosan and fibers, ultimately forming ester bonds. This reaction significantly improves the mechanical strength and hydrophobicity of paper straws. The composite paper straws demonstrate exceptional mechanical properties, including a tensile strength of 47.21 MPa, Young's modulus of 4.33 GPa, and flexural strength of 32.38 MPa. Notably, its water stability is greatly enhanced, with a wet tensile strength of 40.66 MPa, surpassing commercial paper straws by 8 folds. Furthermore, the composite straw achieves complete biodegradability within 120 days, outperforming conventional paper straws in terms of environmental impact. This innovative solution presents a promising and sustainable alternative to plastic straws, addressing the urgent need for eco-friendly products.

Pickering emulsion stabilization with colloidal lignin is enhanced by salt-induced networking in the aqueous phase.

We study the effect of electrolytes on the stability in aqueous media of spherical lignin particles (LP) and its relevance to Pickering emulsion stabilization. Factors considered included the role of ionic strength on morphology development, LP size distribution, surface charge, interfacial adsorption, colloidal and wetting behaviors. Stable emulsions are formed at salt concentrations as low as 50 mM, with the highest stability observed at a critical concentration (400 mM). We show salt-induced destabilization of LP aqueous dispersions at an ionic strength >400 mM. At this critical concentration LP flocculation takes place and particulate networks are formed. This has a profound consequence on the stability of LP-stabilized Pickering emulsions, affecting rheology and long-term stability. The results along with quartz microgravimetry and confocal microscopy observations suggest a possible mechanism for stabilization that considers the interfacial adsorption of LP at oil/water interfaces. The often-unwanted colloidal LP destabilization in water ensues remarkably stable Pickering emulsions by the effect of network formation.

On rheological properties of disc-shaped cellulose nanocrystals.

The rheological properties of a substance depend greatly on its morphology, and rod-shaped cellulose nanocrystals (RCNCs) and cellulose nanofibrils (CNFs) have been extensively studied for their rheological properties. Nevertheless, the rheological properties of disc-shaped cellulose nanocrystals (DCNCs) with crystalline allomorph II derived from mercerized cellulose remain unknown yet. This work investigated the DCNCs' rheological properties in depth using steady-shear and oscillation measurements. At the same concentration, DCNC's suspension viscosity is lower than that of RCNC; RCNC has an instinct viscosity of 258.2, while DCNC has 187.9. Comparing RCNC suspensions with cellulose nanorods, DCNC has a lower aspect ratio and exhibits a distinct steady shear behavior. Under polarized film, DCNC suspension cannot self-assemble into chiral or liquid crystal phases, and with increasing concentrations, the system transitions from an isotropic phase to a gel phase. Oscillation sweeps demonstrate that the gel transition occurs at 7 %-8 %. Based on thixotropic recovery sweep outcomes, the high-stress oscillations enhance the network structure of DCNC suspensions, which is significantly different from that of RCNC suspensions. Results demonstrate the unique properties of DCNC, highlighting its application as a rheological modifier.

High-substituted hydroxypropyl cellulose prepared by homogeneous method and its clouding and self-assembly behaviors.

Hydroxypropyl cellulose (HPC) is a sustainable cellulose derivative valued for its excellent biocompatibility and solubility and is widely used in various fields. Recent scientific research on high-substituted HPC mainly focused on its efficient preparation and phase transition behavior. Herein, a novel strategy of high-substituted HPC synthesis was demonstrated by employing DMSO/TBAF·3H2O as a cellulose solvent, exhibiting more efficiency than traditional approaches. High-substituted HPC prepared has remarkable thermal stability, exceptional hydrophilicity, and satisfactory solubility. Phase transition behavior of HPC with varying molar degrees of substitution (MS) was delved and a notable negative correlation between MS and cloud point temperature (TCP), was revealed, particularly evident at an MS of 12.3, where the TCP drops to 33 °C. Moreover, a unique self-assembly behavior featuring structural color and responsiveness to force in a solvent-free environment emerged when the MS exceeded 10.4. These insights comprehensively strengthen the understanding and knowledge of high-substituted HPC, simultaneously paving the way for further HPC investigation and exploitation.

Effects of hydrolysis conditions on the morphology of cellulose II nanocrystals (CNC-II) derived from mercerized microcrystalline cellulose.

The properties of cellulose nanocrystals with allomorph II (CNC-II) vary with the sources and the treatments received. In this work, the influences of hydrolysis time, temperature, and the applied acid concentration on the crystal size of CNC-II were investigated by the surface response experimental design. The results showed that temperature was the most significant factor affecting the crystal size of CNC-II during hydrolysis from mercerized cellulose. Then the morphology and colloidal properties of CNC-II were revealed by dynamic laser scattering (DLS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), etc. XRD results indicated that CNC-II had slightly lower crystallinity (80.89 % vs 82.7 %) and larger crystallite size (5.21 vs. 5.13 nm) than CNC-I. TEM and AFM results showed that the morphology of CNC-II were disc-like and rod-like particles, with an average diameter of 14.6 ± 4.7 nm (TEM) and a thickness of 4- 8 nm (AFM). TG and XPS revealed the reduced thermal stability was due to the introduced sulfate groups in CNC-II during hydrolysis. This investigation has addressed the features of CNC-II derived from mercerized cellulose, and it would be promising in fabricating advanced materials.

Preparation of magnetic cationic Schiff base polymeric material for highly selective enrichment of avermectins from surface water and milk samples.

Herein, a magnetic cationic Schiff base polymeric material (Fe3O4@SiO2-Schiff-TAPB-DA) was fabricated simply and rapidly, which was explored as a magnetic adsorbent for magnetic solid-phase extraction (MSPE) for enriching seven avermectins insecticides in surface water and milk matrices combined with ultra-high performance liquid chromatography mass spectrometry (UPLC-MS/MS). Under the optimized pretreatment and instrumental parameters, the analytes showed good linearity in the range of 0.5-200.0 ng·mL-1 with a correlation coefficient (R2) greater than 0.9990 and high precision. The limits of detection for the analytes were 0.004-0.047 µg·L-1 for surface water sample and 0.008-0.250 µg·kg-1 for milk samples. Satisfactory recoveries of spiked target compounds were in the range of 82.25- 100.87 % for surface water sample and 72.73- 119.62 % for milk samples. The results indicated powerfully Fe3O4@SiO2-Schiff-TAPB-DA was of significant potential as an MSPE adsorbent for the detection of avermectin insecticides in surface water and milk, which provides a quick and efficient idea for enriching avermectins insecticides in complicated matrices.

Microenvironment-induced CREPT expression by cancer-derived small extracellular vesicles primes field cancerization.

Rationale: Cancer local recurrence increases the mortality of patients, and might be caused by field cancerization, a pre-malignant alteration of normal epithelial cells. It has been suggested that cancer-derived small extracellular vesicles (CDEs) may contribute to field cancerization, but the underlying mechanisms remain poorly understood. In this study, we aim to identify the key regulatory factors within recipient cells under the instigation of CDEs. Methods: In vitro experiments were performed to demonstrate that CDEs promote the expression of CREPT in normal epithelial cells. TMT-based quantitative mass spectrometry was employed to investigate the proteomic differences between normal cells and tumor cells. Loss-of-function approaches by CRISPR-Cas9 system were used to assess the role of CREPT in CDEs-induced field cancerization. RNA-seq was performed to explore the genes regulated by CREPT during field cancerization. Results: CDEs promote field cancerization by inducing the expression of CREPT in non-malignant epithelial cells through activating the ERK signaling pathway. Intriguingly, CDEs failed to induce field cancerization when CREPT was deleted, highlighting the importance of CREPT. Transcriptomic analyses revealed that CDEs elicited inflammatory responses, primarily through activation of the TNF signaling pathway. CREPT, in turn, regulates the transduction of downstream signals of TNF by modulating the expression of TNFR2 and PI3K, thereby promoting inflammation-to-cancer transition. Conclusion: CREPT not only serves as a biomarker for field cancerization, but also emerges as a target for preventing the cancer local recurrence.

Understanding the promoting effect of non-catalytic protein on enzymatic hydrolysis efficiency of lignocelluloses.

Lignin deposits formed on the surface of pretreated lignocellulosic substrates during acidic pretreatments can non-productively adsorb costly enzymes and thereby influence the enzymatic hydrolysis efficiency of cellulose. In this article, peanut protein (PP), a biocompatible non-catalytic protein, was separated from defatted peanut flour (DPF) as a lignin blocking additive to overcome this adverse effect. With the addition of 2.5 g/L PP in enzymatic hydrolysis medium, the glucose yield of the bamboo substrate pretreated by phenylsulfonic acid (PSA) significantly increased from 38 to 94% at a low cellulase loading of 5 FPU/g glucan while achieving a similar glucose yield required a cellulase loading of 17.5 FPU/g glucan without PP addition. Similar promotion effects were also observed on the n-pentanol-pretreated bamboo and PSA-pretreated eucalyptus substrates. The promoting effect of PP on enzymatic hydrolysis was ascribed to blocking lignin deposits via hydrophobic and/or hydrogen-bonding interactions, which significantly reduced the non-productive adsorption of cellulase onto PSA lignin. Meanwhile, PP extraction also facilitated the utilization of residual DPF as the adhesive for producing plywood as compared to that without protein pre-extraction. This scheme provides a sustainable and viable way to improve the value of woody and agriculture biomass. Peanut protein, a biocompatible non-catalytic protein, can block lignin, improve enzymatic hydrolysis efficiency and thereby facilitate the economics of biorefinery.