Cinobufotalin Capsule Combined with Zoledronic Acid in the Treatment of Pain Symptoms and Clinical Efficacy in Prostate Cancer Patients with Bone Metastases: A Retrospective Study.

OBJECTIVE: To retrospectively analyse the effects of cinobufotalin capsule combined with zoledronic acid on pain symptoms and clinical efficacy of prostate cancer patients with bone metastases. METHODS: Patients with prostate cancer with bone metastasis admitted to our hospital from January 2021 to December 2022 were selected as study subjects. They were divided into the control group (treated with zoledronic acid) and the combined group (cinobufotalin capsules were added on the control group basis) according to different recorded treatment methods. The efficacies of the two groups after matching, lumbar L1-4 bone mineral density (BMD), serum calcium, serum phosphorus, visual analogue scale (VAS) score and Karnofsky performance status (KPS) score before and after treatment were compared, and adverse reactions were statistically analysed. RESULTS: A total of 102 patients were included in the study, encompassing 52 patients in the combined group and 50 patients in the control group. After 1:1 preference score matching, 64 patients were included in the two groups. No significant difference in baseline data was found between the two groups (p > 0.05). The total effective rate of the combination group was higher than that of the control group (p < 0.05). No significant differences in L1-4 bone mineral density, serum calcium and phosphorus, VAS score and KPS score were observed between the two groups prior to treatment (p > 0.05). After treatment, the L1-4 bone mineral density (BMD) and KPS score of the combined group decreased to less than those of the control group, the VAS score was lower than that of the control group, and the serum calcium and phosphorus level increased but less than that of the control group (p < 0.05). No significant difference in adverse reactions was found between the two groups (p > 0.05). CONCLUSIONS: Cinobufotalin capsule combined with zoledronic acid had ideal efficacy in the treatment of prostate cancer in patients with bone metastasis. This approach could improve their bone density and quality of life, improve their calcium and phosphorus metabolism, reduce their pain symptoms and provide increased safety. It may have an important guiding role in formulating future clinical treatment plans for patients with prostate cancer and bone metastasis.

Microglia and macrophages alterations in the CNS during acute SIV infection: a single-cell analysis in rhesus macaques.

Human Immunodeficiency Virus (HIV) is widely acknowledged for its profound impact on the immune system. Although HIV primarily affects peripheral CD4 T cells, its influence on the central nervous system (CNS) cannot be overlooked. Within the brain, microglia and CNS-associated macrophages (CAMs) serve as the primary targets for HIV, as well as for the simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects and the establishment of a viral reservoir. Given the gaps in our understanding of how these cells respond in vivo to acute CNS infection, we conducted single-cell RNA sequencing (scRNA-seq) on myeloid cells from the brains of three rhesus macaques 12-days after SIV infection, along with three uninfected controls. Our analysis revealed six distinct microglial clusters including homeostatic microglia, preactivated microglia, and activated microglia expressing high levels of inflammatory and disease-related molecules. In response to acute SIV infection, the population of homeostatic and preactivated microglia decreased, while the activated and disease-related microglia increased. All microglial clusters exhibited upregulation of MHC class I molecules and interferon-related genes, indicating their crucial roles in defending against SIV during the acute phase. All microglia clusters also upregulated genes linked to cellular senescence. Additionally, we identified two distinct CAM populations: CD14lowCD16hi and CD14hiCD16low CAMs. Interestingly, during acute SIV infection, the dominant CAM population changed to one with an inflammatory phenotype. Notably, specific upregulated genes within one microglia and one macrophage cluster were associated with neurodegenerative pathways, suggesting potential links to neurocognitive disorders. This research sheds light on the intricate interactions between viral infection, innate immune responses, and the CNS, providing valuable insights for future investigations.

Spatiotemporal Concurrent PARP Inhibitor Sensitization Based on Radiation-Responsive Nanovesicles for Lung Cancer Chemoradiotherapy.

The implementation of chemoradiation combinations has gained great momentum in clinical practices. However, the full utility of this paradigm is often restricted by the discordant tempos of action of chemotherapy and radiotherapy. Here, a gold nanoparticle-based radiation-responsive nanovesicle system loaded with cisplatin and veliparib, denoted as CV-Au NVs, is developed to augment the concurrent chemoradiation effect in a spatiotemporally controllable manner of drug release. Upon irradiation, the in situ generation of •OH induces the oxidation of polyphenylene sulfide from being hydrophobic to hydrophilic, resulting in the disintegration of the nanovesicles and the rapid release of the entrapped cisplatin and veliparib (the poly ADP-ribose polymerase (PARP) inhibitor). Cisplatin-induced DNA damage and the impairment of the DNA repair mechanism mediated by veliparib synergistically elicit potent pro-apoptotic effects. In vivo studies suggest that one-dose injection of the CV-Au NVs and one-time X-ray irradiation paradigm effectively inhibit tumor growth in the A549 lung cancer model. This study provides new insight into designing nanomedicine platforms in chemoradiation therapy from a vantage point of synergizing both chemotherapy and radiation therapy in a spatiotemporally concurrent manner.

Controlling sodium chloride concentration modulates the supramolecular structure and sol features of wheat starch-acetylated starch binary matrix.

The sol performance of wheat starch (WS) matrix incorporating acetylated starch (AS) is crucial for the processing and quality features of wheat products. From a supramolecular structure view, how regulating salt (sodium chloride) concentration modulates the sol features, e.g., pasting, zero-shear viscosity (ZSV) and thixotropy of WS-AS binary matrix was explored. Compared to the salt-free counterpart, the saline matrices exhibited a delayed pasting profile and a decreased viscoelasticity. Thereinto, the sol at 0.02 M NaCl exhibited the smallest ZSV (23,710 Pa·s) and the greatest in-shear recovery ratio (33.7 %). Such variations could be attributed to the weakened coil-helix, nematic-smectic and isotropy-anisotropy transitions from a side-chain liquid-crystalline perspective. Meanwhile, the correlation length (ξ) and radius of gyration (Rg) obtained from small angle X-ray scattering analysis were increased by 5.2 and 9.6 Å respectively, which disclosed a restrained entanglement and an enhanced chain mobility. These results would provide a reference for the design of fluid/semisolid products with optimized qualities.

Characterization of primary small intestinal lymphoma: a retrospective study based on double balloon endoscopy.

BACKGROUND: The diagnosis of primary small intestinal lymphoma (PSIL) is difficult. This study aimed to evaluate the clinical, radiological and endoscopic characteristics of PSIL and provide clue for diagnosis. METHODS: A total of 30 patients diagnosed with PSIL who underwent double balloon endoscopy (DBE) in the First Affiliated Hospital of Zhejiang University were retrospectively analyzed. Clinical, radiological and endoscopic data were collected. Univariate analysis was used to determine significant indicators for differentiating three main subtypes of PSIL. Cox regression analysis was performed to assess the risk factors for survival. RESULTS: In this study, 10 patients were pathologically diagnosed as diffuse large B-cell lymphoma (DLBCL), 11 were indolent B-cell lymphoma (BCL) and 9 were T-cell lymphoma (TCL). Compared with DLBCL patients, the body mass index (BMI) of TCL patients was significantly lower (p = 0.004). Meanwhile, compared with patients with DLBCL, the patients with indolent BCL had lower levels of C-reactive protein, lactate dehydrogenase (LDH), fibrinogen and D-Dimer (p = 0.004, p = 0.004, p = 0.006, and p = 0.002, respectively), and lower proportion of thicker intestinal wall and aneurysmal dilation in CT scan (p = 0.003 and p = 0.020, respectively). In terms of ulcer morphology, patients with DLBCL had significantly higher proportion of deep ulcers than patients with indolent BCL (p = 0.020, respectively). Cox regression analysis showed that drink (p = 0.034), concomitant colonic ulcers (p = 0.034) and elevated LDH (p = 0.043) are risk factors for mortality in patients with PSIL. CONCLUSIONS: This study provides clinical characteristics of patients with PSIL. Thicker intestinal wall and aneurismal dilation detected on CT scan and deeper ulcer on DBE examination helps to establish a diagnosis of DLBCL.

Nanomaterials modulate tumor-associated macrophages for the treatment of digestive system tumors.

The treatment of digestive system tumors presents challenges, particularly in immunotherapy, owing to the advanced immune tolerance of the digestive system. Nanomaterials have emerged as a promising approach for addressing these challenges. They provide targeted drug delivery, enhanced permeability, high bioavailability, and low toxicity. Additionally, nanomaterials target immunosuppressive cells and reshape the tumor immune microenvironment (TIME). Among the various cells in the TIME, tumor-associated macrophages (TAMs) are the most abundant and play a crucial role in tumor progression. Therefore, investigating the modulation of TAMs by nanomaterials for the treatment of digestive system tumors is of great significance. Here, we present a comprehensive review of the utilization of nanomaterials to modulate TAMs for the treatment of gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer. We also investigated the underlying mechanisms by which nanomaterials modulate TAMs to treat tumors in the digestive system. Furthermore, this review summarizes the role of macrophage-derived nanomaterials in the treatment of digestive system tumors. Overall, this research offers valuable insights into the development of nanomaterials tailored for the treatment of digestive system tumors.

Quality prediction of whole-grain rice noodles using backpropagation artificial neural network.

BACKGROUND: Whole-grain rice noodles are a kind of healthy food with rich nutritional value, and their product quality has a notable impact on consumer acceptability. The quality evaluation model is of great significance to the optimization of product quality. However, there are few methods that can establish a product quality prediction model with multiple preparation conditions as inputs and various quality evaluation indexes as outputs. In this study, an artificial neural network (ANN) model based on a backpropagation (BP) algorithm was used to predict the comprehensive quality changes of whole-grain rice noodles under different preparation conditions, which provided a new way to improve the quality of extrusion rice products. RESULTS: The results showed that the BP-ANN using the Levenberg-Marquardt algorithm and the optimal topology (4-11-8) gave the best performance. The correlation coefficients (R2) for the training, validation, testing, and global data sets of the BP neural network were 0.927, 0.873, 0.817, and 0.903, respectively. In the validation test, the percentage error in the quality prediction of whole-grain rice noodles was within 10%, indicating that the BP-ANN could accurately predict the quality of whole-grain rice noodles prepared under different conditions. CONCLUSION: This study showed that the quality prediction model of whole-grain rice noodles based on the BP-ANN algorithm was effective, and suitable for predicting the quality of whole-grain rice noodles prepared under different conditions. © 2024 Society of Chemical Industry.

Machine learning-enabled high-throughput industry screening of edible oils.

Long-term consumption of mixed fraudulent edible oils increases the risk of developing of chronic diseases which has been a threat to the public health globally. The complicated global supply-chain is making the industry malpractices had often gone undetected. In order to restore the confidence of consumers, traceability (and accountability) of every level in the supply chain is vital. In this work, we shown that machine learning (ML) assisted windowed spectroscopy (e.g., visible-band, infra-red band) produces high-throughput, non-destructive, and label-free authentication of edible oils (e.g., olive oils, sunflower oils), offers the feasibility for rapid analysis of large-scale industrial screening. We report achieving high-level of discriminant (AUC > 0.96) in the large-scale (n ≈ 11,500) of adulteration in olive oils. Notably, high clustering fidelity of 'spectral fingerprints' achieved created opportunity for (hypothesis-free) self-sustaining large database compilation which was never possible without machine learning. (137 words).

Structural characteristics of ß-glucans from various sources and their influences on the short- and long-term starch retrogradation in wheat flour.

Beta-glucans possess the ability of retarding starch retrogradation. However, ß-glucans from different sources might show various influences on retrogradation process and the structure-function relationships of ß-glucans related to the feature still remains unclear. In the study, the ß-glucans from oat (OG), highland barley (HBG), and yeast (YG) were selected. Each ß-glucans formed aggregate as observed by atomic force microscopy. OG and HBG with a lower Mw aggregated more obviously and exhibited higher intrinsic and apparent viscosity. The two ß-glucans showed more restraining effect on the short-term starch retrogradation in the sol-like test system (RVA) and the long-term starch retrogradation in the gel-like test system (DSC). However, YG with a higher Mw exerted a greater retarding effect on the short-term starch retrogradation in gel-like test systems (Mixolab and rheology). LF-NMR indicated that OG and HBG increased the population of less-bound water by wrapping around the starch. In summary, the structural characteristics of ß-glucan (Mw and aggregation state) and experiment condition (solid content) jointly influenced starch retrogradation, because a lower Mw and higher aggregation capacity ß-glucan interacted more readily with starch and inhibited more starch re-association due to the higher diffusion rate in the sol-like system.

The miR6445-NAC029 module regulates drought tolerance by regulating the expression of glutathione S-transferase U23 and reactive oxygen species scavenging in Populus.

MicroRNAs are essential in plant development and stress resistance, but their specific roles in drought stress require further investigation. Here, we have uncovered that a Populus-specific microRNAs (miRNA), miR6445, targeting NAC (NAM, ATAF, and CUC) family genes, is involved in regulating drought tolerance of poplar. The expression level of miR6445 was significantly upregulated under drought stress; concomitantly, seven targeted NAC genes showed significant downregulation. Silencing the expression of miR6445 by short tandem target mimic technology significantly decreased the drought tolerance in poplar. Furthermore, 5' RACE experiments confirmed that miR6445 directly targeted NAC029. The overexpression lines of PtrNAC029 (OE-NAC029) showed increased sensitivity to drought compared with knockout lines (Crispr-NAC029), consistent with the drought-sensitive phenotype observed in miR6445-silenced strains. PtrNAC029 was further verified to directly bind to the promoters of glutathione S-transferase U23 (GSTU23) and inhibit its expression. Both Crispr-NAC029 and PtrGSTU23 overexpressing plants showed higher levels of PtrGSTU23 transcript and GST activity while accumulating less reactive oxygen species (ROS). Moreover, poplars overexpressing GSTU23 demonstrated enhanced drought tolerance. Taken together, our research reveals the crucial role of the miR6445-NAC029-GSTU23 module in enhancing poplar drought tolerance by regulating ROS homeostasis. This finding provides new molecular targets for improving the drought resistance of trees.

Changing the ionic strength can regulate the resistant starch content of binary complex including starch and protein or its hydrolysates.

Ionic strength condition is a crucial parameter for food processing, but it remains unclear how ionic strength alters the structure and digestibility of binary complexes containing starch and protein/protein hydrolysates. Here, the binary complex with varied ionic strength (0-0.40 M) was built by native corn starch (NS) and soy protein isolate (SPI)/hydrolysates (SPIH) through NaCl. The inclusion of SPI and SPIH allowed a compact network structure, especially the SPIH with reduced molecule size, which enriched the resistant starch (RS) of NS-SPIH. Particularly, the higher ionic strength caused the larger nonperiodic structures and induced loosener network structures, largely increasing the possibility of amylase for starch digestion and resulting in a decreased RS content from 19.07 % to 15.52 %. In other words, the SPIH hindered starch digestion while increasing ionic strength had the opposite effect, which should be considered in staple food production.

HIV Infection Drives Foam Cell Formation via NLRP3 Inflammasome Activation.

Persistent immune activation is linked to an increased risk of cardiovascular disease (CVD) in people with HIV (PWH) on antiretroviral therapy (ART). The NLRP3 inflammasome may contribute to elevated CVD risk in PWH. This study utilized peripheral blood mononuclear cells (PBMCs) from 25 PWH and 25 HIV-negative controls, as well as HIV in vitro infections. Transcriptional changes were analyzed using RNAseq and pathway analysis. Our results showed that in vitro HIV infection of macrophages and PBMCs from PWH had increased foam cell formation and expression of the NLRP3 inflammasome components and downstream cytokines (caspase-1, IL-1ß, and IL-18), which was reduced with inhibition of NLRP3 activity using MCC950. Transcriptomic analysis revealed an increased expression of multiple genes involved in lipid metabolism, cholesterol storage, coronary microcirculation disorders, ischemic events, and monocyte/macrophage differentiation and function with HIV infection and oxLDL treatment. HIV infection and NLRP3 activation increased foam cell formation and expression of proinflammatory cytokines, providing insights into the mechanisms underlying HIV-associated atherogenesis. This study suggests that HIV itself may contribute to increased CVD risk in PWH. Understanding the involvement of the inflammasome pathway in HIV atherosclerosis can help identify potential therapeutic targets to mitigate cardiovascular risks in PWH.

Study by means of 1H nuclear magnetic resonance of the oxidation process in high oleic sunflower oil and palm oil during deep-frying of fish cakes.

This study aimed to compare the frying performance of palm oil (PO) and high oleic sunflower oil (HOSO) during frying aquatic products. The quality change and frying performance of HOSO and PO during frying of fish cakes were investigated. The oxidation and hydrolysis products of both oils were explored by the nuclear magnetic resonance technique. The results showed that the color deepening rate of PO was higher than that of HOSO. After 18 h of frying, the total polar compound content of PO and HOSO reached 25.67% and 27.50%, respectively. HOSO had lower degree of oxidation than PO after 24 h of continuous frying. The polyunsaturated fatty acid content in HOSO and PO significantly decreased. The oleic acid content in HOSO remained above 80% during the frying process. The major aldehydes in both oils were (E, E)-2,4-alkadienals and n-alkanals and glycerol diesters (DAGs) were abundant in PO. Furthermore, the addition of fish cakes had slight effect on the quality of the frying oil. Therefore, HOSO is an appropriate candidate for frying owing to its excellent frying stability and nutritional value.

Resistive Memory Devices at the Thinnest Limit: Progress and Challenges.

The Si-based integrated circuits industry has been developing for more than half a century, by focusing on the scaling-down of transistor. However, the miniaturization of transistors will soon reach its physical limits, thereby requiring novel material and device technologies. Resistive memory is a promising candidate for in-memory computing and energy-efficient synaptic devices that can satisfy the computational demands of the future applications. However, poor cycle-to-cycle and device-to-device uniformities hinder its mass production. 2D materials, as a new type of semiconductor, is successfully employed in various micro/nanoelectronic devices and have the potential to drive future innovation in resistive memory technology. This review evaluates the potential of using the thinnest advanced materials, that is, monolayer 2D materials, for memristor or memtransistor applications, including resistive switching behavior and atomic mechanism, high-frequency device performances, and in-memory computing/neuromorphic computing applications. The scaling-down advantages of promising monolayer 2D materials including graphene, transition metal dichalcogenides, and hexagonal boron nitride are presented. Finally, the technical challenges of these atomic devices for practical applications are elaborately discussed. The study of monolayer-2D-material-based resistive memory is expected to play a positive role in the exploration of beyond-Si electronic technologies.

Magnetic Bimetallic Heterointerface Nanomissiles with Enhanced Microwave Absorption for Microwave Thermal/Dynamics Therapy of Breast Cancer.

Microwave thermotherapy (MWT) has shown great potential in cancer treatment due to its deep tissue penetration and minimally invasive nature. However, the poor microwave absorption (MA) properties of the microwave thermal sensitizer in the medical frequency band significantly limit the thermal effect of MWT and then weaken the therapeutic efficacy. In this paper, a Ni-based multilayer heterointerface nanomissile of MOFs-Ni-Ru@COFs (MNRC) with improved MA performance in the desired frequency band via introducing magnetic loss and dielectric loss is developed for MWT-based treatment. The loading of the Ni nanoparticle in MNRC mediates the magnetic loss, introducing the MA in the medical frequency band. The heterointerface formed in the MNRC by nanoengineering induces significant interfacial polarization, increasing the dielectric loss and then enhancing the generated MA performance. Moreover, MNRC with the strong MA performance in the desired frequency range not only enhances the MW thermal effect of MWT but also facilitates the electron and energy transfer, generating reactive oxygen species (ROS) at tumor sites to mediate microwave dynamic therapy (MDT). The strategy of strengthening the MA performance of the sensitizer in the medical frequency band to improve MWT-MDT provides a direction for expanding the clinical application of MWT in tumor treatment.

Tunable Zeolitic Imidazolate Framework-8 Nanoparticles for Biomedical Applications.

Zeolite imidazole framework-8 (ZIF-8) is the most prestigious one among zeolitic imidazolate framework (ZIF) with tunable dimensions and unique morphological features. Utilizing its synthetic adjustability and structural regularity, ZIF-8 exhibits enhanced flexibility, allowing for a wide range of functionalities, such as loading of nanoparticle components while preserving biomolecules activity. Extensive efforts are made from investigating synthesis techniques to develop novel applications over decades. In this review, the development and recent progress of various synthesis approaches are briefly summarized. In addition, its interesting properties such as adjustable porosity, excellent thermal, and chemical stabilities are introduced. Further, five representative biomedical applications are highlighted based on above physicochemical properties. Finally, the remaining challenges and offered insights into the future outlook are also discussed. This review aims to understand the co-relationships between structures and biomedical functionalities, offering the opportunity to construct attractive materials with promising characteristics.

TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/ß-catenin Signaling Pathway.

OBJECTIVE: To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) and celastrol combination treatment (TCCT) in glioblastoma cells. METHODS: Cell counting kit-8 was used to detect the effects of different concentrations of celastrol (0-16 µmol/L) and TRAIL (0-500 ng/mL) on the cell viability of glioblastoma cells. U87 cells were randomly divided into 4 groups, namely control, TRAIL (TRAIL 100 ng/mL), Cel (celastrol 0.5 µmol/L) and TCCT (TRAIL 100 ng/mL+ celastrol 0.5 µmol/L). Cell proliferation, migration, and invasion were detected by colony formation, wound healing, and Transwell assays, respectively. Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition (EMT) markers (zona occludens, N-cadherin, vimentin, zinc finger E-box-binding homeobox, Slug, and ß-catenin). Wnt pathway was activated by lithium chloride (LiCl, 20 mol/L) and the mechanism for action of TCCT was explored. RESULTS: Celastrol and TRAIL synergistically inhibited the proliferation, migration, invasion, and EMT of U87 cells (P<0.01). TCCT up-regulated the expression of GSK-3ß and down-regulated the expression of ß-catenin and its associated proteins (P<0.05 or P<0.01), including c-Myc, Cyclin-D1, and matrix metalloproteinase (MMP)-2. In addition, LiCl, an activator of the Wnt signaling pathway, restored the inhibitory effects of TCCT on the expression of ß-catenin and its downstream genes, as well as the migration and invasion of glioblastoma cells (P<0.05 or P<0.01). CONCLUSIONS: Celastrol and TRAIL can synergistically suppress glioblastoma cell migration, invasion, and EMT, potentially through inhibition of Wnt/ß-catenin pathway. This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

Structural Characterization and Immunomodulatory Activity of a Mannose-Rich Polysaccharide Isolated from Bifidobacterium breve H4-2.

In this study, a novel homogeneous mannose-rich polysaccharide named EPS-1 from the fermentation broth of Bifidobacterium breve H4-2 was isolated and purified by anion exchange column chromatography and gel column chromatography. The primary structure of EPS-1 was analyzed by high-performance liquid chromatography, Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry, and nuclear magnetic resonance. The results indicated that EPS-1 had typical functional groups of polysaccharides. EPS-1 with an average molecular weight of 3.99 × 104 Da was mainly composed of mannose (89.65%) and glucose (5.84%). The backbone of EPS-1 was →2,6)-α-d-Manp-(1→2)-α-d-Manp-(1→2,6)-α-d-Manp-(1→2)-α-d-Manp-(1→2,6)-α-d-Manp-(1→6)-α-d-Glcp-(1→ simultaneously containing two kinds of branched chains (α-d-Manp-(1→3)-α-d-Manp-(1→ and α-d-Manp-(1→). Besides, EPS-1 had a triple-helical conformation and exhibited excellent thermal stability. Moreover, the immunomodulatory activity of EPS-1 was evaluated by RAW 264.7 cells. Results indicated that EPS-1 significantly enhanced the viability of RAW 264.7 cells. EPS-1 could also be recognized by toll-like receptor 4, thereby activating the nuclear factors-κB (NF-κB) signaling pathway, promoting phosphorylation of related nuclear transcription factors, improving cell phagocytic activity, and promoting the secretion of NO, IL-6, IL-1ß, and TNF-α. Thus, EPS-1 could activate the TLR4-NF-κB signaling pathway to emerge immunomodulatory activity on macrophages. The above results indicate that EPS-1 can serve as a potential immune-stimulating polysaccharide.

New Technologies in Cereal Processing and Their Impact on the Physical Properties of Cereal Foods.

Cereal is a general term for cereal plants or food crops, covering a wide range of foods, including rice, wheat, millet, corn and other miscellaneous grains, and representiing the most important component of the human diet [...].

Critical contributions of protein cargos to the functions of macrophage-derived extracellular vesicles.

BACKGROUND: Macrophages are highly plastic innate immune cells that play key roles in host defense, tissue repair, and homeostasis maintenance. In response to divergent stimuli, macrophages rapidly alter their functions and manifest a wide polarization spectrum with two extremes: M1 or classical activation and M2 or alternative activation. Extracellular vesicles (EVs) secreted from differentially activated macrophages have been shown to have diverse functions, which are primarily attributed to their microRNA cargos. The role of protein cargos in these EVs remains largely unexplored. Therefore, in this study, we focused on the protein cargos in macrophage-derived EVs. RESULTS: Naïve murine bone marrow-derived macrophages were treated with lipopolysaccharide or interlukin-4 to induce M1 or M2 macrophages, respectively. The proteins of EVs and their parental macrophages were subjected to quantitative proteomics analyses, followed by bioinformatic analyses. The enriched proteins of M1-EVs were involved in proinflammatory pathways and those of M2-EVs were associated with immunomodulation and tissue remodeling. The signature proteins of EVs shared a limited subset of the proteins of their respective progenitor macrophages, but they covered many of the typical pathways and functions of their parental cells, suggesting their respective M1-like and M2-like phenotypes and functions. Experimental examination validated that protein cargos in M1- or M2-EVs induced M1 or M2 polarization, respectively. More importantly, proteins in M1-EVs promoted viability, proliferation, and activation of T lymphocytes, whereas proteins in M2-EVs potently protected the tight junction structure and barrier integrity of epithelial cells from disruption. Intravenous administration of M2-EVs in colitis mice led to their accumulation in the colon, alleviation of colonic inflammation, promotion of M2 macrophage polarization, and improvement of gut barrier functions. Protein cargos in M2-EVs played a key role in their protective function in colitis. CONCLUSION: This study has yielded a comprehensive unbiased dataset of protein cargos in macrophage-derived EVs, provided a systemic view of their potential functions, and highlighted the important engagement of protein cargos in the pathophysiological functions of these EVs.