Deubiquitination of aryl hydrocarbon receptor (AhR) by USP21 negatively regulates Th17 cells differentiation.

Aryl hydrocarbon receptor (AhR) is a key transcription factor that modulates the differentiation of T helper 17 (Th17) cells. How AhR is regulated at the post-translational level in Th17 cells remains largely unclear. Here we identify USP21 as a newly defined deubiquitinase of AhR. We demonstrate that USP21 interacts with and stabilizes AhR by removing the K48-linked polyubiquitin chains from AhR. Interestingly, USP21 inhibits the transcriptional activity of AhR in a deubiquitinating-dependent manner. USP21 deubiquitinates AhR at the K432 residue, and the maintenance of ubiquitination on this site is required for the intact transcriptional activity of AhR. Moreover, the deficiency of USP21 promotes the differentiation of Th17 cells both in vitro and in vivo. Consistently, adoptive transfer of USP21 deficient naïve CD4+ T cells elicits more severe colitis in Rag1-/- recipients. Therefore, our study reveals a novel mechanism in which USP21 deubiquitinates AhR and negatively regulates the differentiation of Th17 cells.

A novel highly dispersed calcium silicate hydrate nanosheets for efficient high-concentration Cu2+ adsorption.

Currently, the low cost and effective purification toward heavy metal ions in wastewater has garnered global attention. Herein, we used hydrothermal method to prepare highly dispersed calcium silicate hydrate in fluorite tailings. And the stacking thickness of calcium silicate hydrate layered morphology was less than 5 nm. For high concentration Cu2+ purification investigation in wastewater, we found that the equilibrium adsorption capacity reached 797.92 mg/g via the CSH with 3:2 Ca/Si molar ratio, be 1.43-21.8 times than that of reported data. Therein, the metal-metal exchange and deposition are the primary pathways for Cu2+ adsorption, and electrostatic attraction is the secondary pathway. And the relative ∼100 % removal rate of high-concentration Ni2+ and Cr3+ ions were confirmed via CSH prepared from different tailings. This method offers a cost-effective way to utilize tailings for preparing highly efficient adsorbents toward HMIs removal in wastewater.

Effects of black bean cell wall pectin by exogenous calcium ions: Insight into the metabolomics, physicochemical properties and anti-digestive capacity.

In this work, the metabolomics, physicochemical and in vitro digestion properties of black beans influenced by different calcium ion solutions (0, 0.5 %, 1 %, and 2 %) were explored. The addition of calcium ions had a significant effect on the metabolic processing of black beans, including 16 differential metabolites and 4 metabolic pathways related to the cell wall. From the results of FT-IR and ICP-OES, it was confirmed that calcium ions can interact with COO- in non-methylated galacturonic acid in pectin to form calcium carboxylate strengthening the middle lamellae of the cell wall. Based on this mechanism, the soaked beans with an intact and dense cell structure were verified by the analyses of SEM and CLSM. Compared with other soaked beans, BB-2 exhibited lower cell permeability with electrical conductivity value decreased to 0.60 µs·cm-1. Additionally, BB-2 demonstrated slower digestion properties with digestion rate coefficient at 0.0020 min-1 and digestion extent only at 30.83 %, which is attributed to its increasingly compact cell wall and densely cellular matrix. This study illustrates the effect of calcium ions on the cellular structure of black beans, providing an effective process method for low glycemic index diets.

Stereotactically intracerebral transplantation of neural stem cells for ischemic stroke attenuated inflammatory responses and promoted neurogenesis: an experimental study with monkeys.

BACKGROUND: Ischemic stroke is a common neurovascular disorder with high morbidity and mortality. However, the underlying mechanism of stereotactically intracerebral transplantation of human neural stem cell (hNSC) is not well elucidated. MATERIALS AND METHODS: Four days after ischemic stroke induced by Rose Bengal photo-thrombosis, 7 cynomolgus monkeys were transplanted with hNSCs or vehicles stereotactically and followed up for 84 days. Behavioral assessments, magnetic resonance imaging, blood tests, and pathological analysis were performed before and after treatment. The proteome profiles of the left and right precentral gyrus and hippocampus were evaluated. Extracellular vesicle micro-RNA (miRNA) from the peripheral blood was extracted and analyzed. RESULTS: hNSC transplantation reduced the remaining infarcted lesion volume of cynomolgus monkeys with ischemic stroke without remarkable side effects. Proteomic analyses indicated that hNSC transplantation promoted GABAergic and glutamatergic neurogenesis, and restored the mitochondrial electron transport chain function in the ischemic infarcted left precentral gyrus or hippocampus. Immunohistochemical staining and qRT-PCT confirmed the promoting effects on neurogenesis and revealed that hNSCs attenuated post-infarct inflammatory responses by suppressing resident glia activation and mediating peripheral immune cell infiltration. Consistently, miRNA-sequencing revealed the miRNAs which were related to these pathways were down-regulated after hNSC transplantation. CONCLUSIONS: This study indicates that hNSCs can be effectively and safely used to treat ischemic stroke by promoting neurogenesis, regulating post-infarct inflammatory responses, and restoring mitochondrial function in both the infarct region and hippocampus.

Protective role of fruits of Rosa odorata var. gigantea against WIRS-induced gastric mucosal injury in rats by modulating pathway related to inflammation, oxidative stress and apoptosis.

Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea (FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress (WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved. Methods: A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin (H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot. Results: Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT) contents; anti-inflammatory cytokines interleukin-10 (IL-10) and prostaglandin E2 (PGE2) levels as well as regulatory factors tumor necrosis factor-α (TGF-α) and somatostatin (SS) contents, while decreasing malondialdehyde (MDA), nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), gastrin (GAS) and endothelin (ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen (PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-κB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival. Conclusion: The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis systems.

Cannabinoid receptor 2 selective agonist alleviates systemic sclerosis by inhibiting Th2 differentiation through JAK/SOCS3 signaling.

Systemic sclerosis (SSc) poses a significant challenge in autoimmunology, characterized by the development of debilitating fibrosis of skin and internal organs. The pivotal role of dysregulated T cells, notably the skewed polarization toward Th2 cells, has been implicated in the vascular damage and progressive fibrosis observed in SSc. In this study, we explored the underlying mechanisms by which cannabinoid receptor 2 (CB2) highly selective agonist HU-308 restores the imbalance of T cells to alleviate SSc. Using a bleomycin-induced SSc (BLM-SSc) mouse model, we demonstrated that HU-308 effectively attenuates skin and lung fibrosis by specifically activating CB2 on CD4+ T cells to inhibit the polarization of Th2 cells in BLM-SSc mice, which was validated by Cnr2-specific-deficient mice. Different from classical signaling downstream of G protein-coupled receptors (GPCRs), HU-308 facilitates the expression of SOCS3 protein and subsequently impedes the IL2/STAT5 signaling pathway during Th2 differentiation. The deficiency of SOCS3 partially mitigated the impact of HU-308. Analysis of a cohort comprising 80 SSc patients and 82 healthy controls revealed an abnormal elevation in the Th2/Th1 ratio in SSc patients. The proportion of Th2 cells showed a significant positive correlation with mRSS score and positivity of anti-Scl-70. Administration of HU-308 to PBMCs and peripheral CD4+ T cells from SSc patients led to the upregulation of SOCS3, which effectively suppressed the aberrantly activated STAT5 signaling pathway and the proportion of CD4+IL4+ T cells. In conclusion, our findings unveil a novel mechanism by which the CB2 agonist HU-308 ameliorates fibrosis in SSc by targeting and reducing Th2 responses. These insights provide a foundation for future therapeutic approaches in SSc by modulating Th2 responses.

FOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity.

Targeting tumor-infiltrating regulatory T cells (Tregs) is an efficient way to evoke an anti-tumor immune response. However, how Tregs maintain their fragility and stability remains largely unknown. IFITM3 and STAT1 are interferon-induced genes that play a positive role in the progression of tumors. Here, we showed that IFITM3-deficient Tregs blunted tumor growth by strengthening the tumor-killing response and displayed the Th1-like Treg phenotype with higher secretion of IFNγ. Mechanistically, depletion of IFITM3 enhances the translation and phosphorylation of STAT1. On the contrary, the decreased IFITM3 expression in STAT1-deficient Tregs indicates that STAT1 conversely regulates the expression of IFITM3 to form a feedback loop. Blocking the inflammatory cytokine IFNγ or directly depleting STAT1-IFITM3 axis phenocopies the restored suppressive function of tumor-infiltrating Tregs in the tumor model. Overall, our study demonstrates that the perturbation of tumor-infiltrating Tregs through the IFNγ-IFITM3-STAT1 feedback loop is essential for anti-tumor immunity and constitutes a targetable vulnerability of cancer immunotherapy.

Lamin A/C mediates microglial activation by modulating cell proliferation and immune response.

Lamin A/C is involved in macrophage activation and premature aging, also known as progeria. As the resident macrophage in brain, overactivation of microglia causes brain inflammation, promoting aging and brain disease. In this study, we investigated the role of Lamin A/C in microglial activation and its impact on progeria using Lmna-/- mice, primary microglia, Lmna knockout (Lmna-KO) and Lmna-knockdown (Lmna-KD) BV2 cell lines. We found that the microglial activation signatures, including cell proliferation, morphology changes, and proinflammatory cytokine secretion (IL-1ß, IL-6, and TNF-α), were significantly suppressed in all Lamin A/C-deficient models when stimulated with LPS. TMT-based quantitative proteomic and bioinformatic analysis were further applied to explore the mechanism of Lamin A/C-regulated microglia activation from the proteome level. The results revealed that immune response and phagocytosis were impaired in Lmna-/- microglia. Stat1 was identified as the hub protein in the mechanism by which Lamin A/C regulates microglial activation. Additionally, DNA replication, chromatin organization, and mRNA processing were also altered by Lamin A/C, with Ki67 fulfilling the main hub function. Lamin A/C is a mechanosensitive protein and, the immune- and proliferation-related biological processes are also regulated by mechanotransduction. We speculate that Lamin A/C-mediated mechanotransduction is required for microglial activation. Our study proposes a novel mechanism for microglial activation mediated by Lamin A/C.

Mindfulness training modifies attentional bias to facial emotion and emotional symptoms.

BACKGROUND: Mindfulness training has been shown to improve emotional symptoms such as anxiety and depressive symptoms. However, its cognitive-behavioral mechanism is still unclear. The present study aimed to investigate the effect of mindfulness training on attention to emotional faces and its role in the improvement in emotional symptoms. METHODS: Eighty participants were recruited and randomly divided into a training group (n = 40) that received eight weeks of mindfulness training and a control group (n = 40) that attended a mindfulness lecture. Before training (T1), immediately after training (T2), and three months after training (T3), all participants were asked to complete the Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS) to assess their emotional symptoms and a modified dot-probe task to measure their attention to emotional faces. RESULTS: Mindfulness training significantly reduced anxiety and depressive symptoms at both T2 and T3. After training, the attentional bias toward happy faces increased, while the attentional bias toward sad faces decreased in the training group compared with the control group. Mediation analysis showed that the improvement in attentional bias toward sad faces partially mediated the effect of mindfulness training on depression at T2. LIMITATIONS: Our participants were not a clinical sample (i.e., were not diagnosed with emotional disorders), and the time course of attention components was difficult to examine in the present study. CONCLUSIONS: Mindfulness training can stably reduce anxious and depressive symptoms. However, it may have a temporary effect on attentional bias toward facial emotions, which plays a limited role in improving emotional symptoms.

Coffee Silverskin Cellulose-Based Composite Film with Natural Pigments for Food Packaging: Physicochemical and Sensory Abilities.

To promote a circular economy, the use of agricultural by-products as food packaging material has steadily increased. However, designing food packaging films that meet consumers' preferences and requirements is still a challenge. In this work, cellulose extracted from coffee silverskin (a by-product of coffee roasting) and chitosan were combined with different natural pigments (curcumin, phycocyanin, and lycopene) to generate a variety of composite films with different colors for food packaging. The physicochemical and sensory properties of the films were evaluated. The cellulose/chitosan film showed favorable mechanical properties and water sensitivity. Addition of natural pigments resulted in different film colors, and significantly affected the optical properties and improved the UV-barrier, swelling degree, and water vapor permeability (WVP), but there were also slight decreases in the mechanical properties. The various colored films can influence the perceived features and evoke different emotions from consumers, resulting in films receiving different attraction and liking scores. This work provides a comprehensive evaluation strategy for coffee silverskin cellulose-based composite films with incorporated pigments, and a new perspective on the consideration of the hedonic ratings of consumers regarding bio-based films when designing food packaging.

Extracellular Vesicles Play a Central Role in Cerebral Venous Disease-Associated Brain Atrophy.

Cerebral venous abnormalities, distinct from traditional arterial diseases, have been linked to brain atrophy in a previous community-based cohort study, specifically in relation to the reduction of deep medullary veins (r-DMVs). To better understand the properties and biological functions of serum extracellular vesicles (EVs) in cerebral venous disease-associated brain atrophy, EVs are extracted from the serum of both participants with r-DMV and normal controls and analyzed their proteomic profiles using Tandem Mass Tag label quantitation analysis. Phenotypic experiments showed that EVs from individuals with r-DMVs are able to disrupt the normal functions of neurons, endothelial cells, and smooth muscle cells, and induce A1 reactive astrocytes. Additionally, this study provided a comprehensive characterization of the proteomic profile of DMV EVs and found that the collagen hydroxyproline is upregulated, while complement C3 is downregulated in the r-DMV group, suggesting that r-DMV may not be a simple pathological phenomenon and highlighting the potential involvement of EVs in the progression of brain atrophy in r-DMVs which has implications for the development of future therapeutic strategies.

Effects of curcumin, phycocyanin, or modified lycopene colorants on the physicochemical and sensory properties of whey protein-cellulose nanocrystal packaging films.

To utilize natural hydrophobic/hydrophilic colorants to manufacture good quality and attractive packaging films, we investigated the effects of natural colorants (curcumin, phycocyanin, modified lycopene, and their mixed colorants) on the physicochemical and sensory properties of whey protein isolate-cellulose nanocrystal packaging film. Owing to the improvement in hydrophobicity and spatial density, moisture content (MC) and water vapor permeability (WVP) of films containing curcumin were reduced by 16.91% and 8.49%, respectively, in contrast to that, MC and WVP increased by 10.75% and 4.09%, respectively, in film containing modified lycopene. Mechanical testing, infrared spectra, and X-ray diffraction revealed the retention of structural properties of protein matrix. Rate-All-That-Apply evaluation indicated that films containing colorants enriched tactile and visual sensory characteristics. The eye tracking testing of packed foods showed that preferential attraction depends on the color of the food itself. Thus, a consumer-oriented multi-colored packaging film with good performance was achieved.

The protective effect of quinoa on the gastric mucosal injury induced by absolute ethanol.

BACKGROUND: Gastric mucosal injury caused by ethanol is a common gastrointestinal disease. Quinoa (Chenopodium quinoa Willd.), as a nutrient-rich grain, plays a significant role in preventing and treating gastric mucosal damage. The present study aimed to explore the protective effect of quinoa on alcohol-induced gastric mucosal damage and its possible mechanism. RESULTS: The ethanol-induced gastric mucosal injury rat model was used for in vivo experiments and H2 O2 -induced GES-1 cells for in vitro experiments to elucidate the protective effect of quinoa. The results show that quinoa water extract can increase the superoxide dismutase level and decrease the malondialdehyde level in vitro and in vivo. Furthermore, quinoa also reduced the bleeding point and bleeding area in rats with ethanol-induced gastric mucosal injury and improved gastric histopathological changes. H2 O2 significantly increased the levels of inflammatory factors in GES-1 cells, which were markedly ameliorated by quinoa water extract. Likewise, quinoa water extract regulated the protein expression levels of Nrf2, Keap1, HO-1, p-IKK, and p-NF-κB through Nrf2 and nuclear factor-κB signaling pathways, reducing the production of oxidative stress and inflammation, thereby repairing the damaged gastric mucosa. CONCLUSION: The findings of this study demonstrated that quinoa shows protective effect against ethanol-induced gastric mucosal injury through its anti-inflammatory and anti-oxidant effects. We propose that our research will provide a reference for quinoa as a functional food. © 2022 Society of Chemical Industry.

Physicochemical and Sensory Properties Colored Whey Protein-Cellulose Nanocrystal Edible Films after Freeze-Thaw Treatment.

Balancing physicochemical properties and sensory properties is one of the key points in expanding edible packaging applications. The work consisted of two parts, one was to investigate the effects of cellulose nanocrystals (CNC) on the packaging-related properties of whey protein isolate films with natural colorants (curcumin, phycocyanin, and lycopene) under freeze-thaw (FT) conditions; the other was to test oral tactility and visual sensory properties of the edible films and their overall acceptability in packed ice cream. FT treatment reduced the mechanical strength and moisture content and increased the water vapor permeability of the films, as water-phase transformation not only disrupted hydrogen bonds but also the film network structure through physical stress. The oral tactility produced by CNC and the visual effect produced by colorants could affect participants' preference for edible films. This study provides a good reference for the consumer-driven product development of packaged low-temperature products.

Chemical constituents and pharmacological activities of medicinal plants from Rosa genus.

The genus Rosa (Rosaceae family) includes about 200 species spread in the world, and this genus shows unique advantages in medicine and food. To date, several scholars concentrated on compounds belonging to flavonoids, triterpenes, tannins, polysaccharide, phenolic acids, fatty acids, organic acids, carotenoids, and vitamins. Pharmacological effects such as antineoplastic and anti-cancer properties, anti-inflammatory, antioxidant, liver protection, regulate blood sugar, antimicrobial activity, antiviral activity, as well as nervous system protection and cardiovascular protection were wildly reported. This article reviews the chemical constituents, pharmacological effects, applications and safety evaluations of Rosa plants, which provides a reference for the comprehensive utilization of medicine and food resources and gives a scientific basis for the development of medicinal plants of the genus Rosa.

Regulatory effect of traditional Chinese medicines on signaling pathways of process from chronic atrophic gastritis to gastric cancer.

Chronic atrophic gastritis (CAG), a common disease of digestive system, is an extremely important cause of gastric cancer (GC). The occurrence and development of CAG involves the abnormality of multiple signaling pathways. Traditional Chinese medicines (TCMs) has the advantages of mild action, multi-target and small adverse reaction, etc., which broadens the way for the treatment of the disease, and TCMs can play a therapeutic role by regulating multiple signaling pathways. In this review, based on the related experiments of TCMs and Chinese herbal compounds in recent years, the related literatures were searched and 10 kinds of signaling pathways involved were summarized, in order to provide a reference for further research on reversing or delaying the progress of CAG and preventing gastric cancer.

Neobavaisoflavone inhibits allergic inflammatory responses by suppressing mast cell activation.

Neobavaisoflavone (NBIF), a monomolecular compound extracted from Psoralea corylifolia (Leguminosae), is commonly used in traditional Chinese medicine for multiple purposes. NBIF is known to exert anti-fungal and anti-tumor effects, and promote bone formation. Whether NBIF exhibits anti-allergic effects by regulating mast cell activation remains unclear. Therefore, we designed this study to investigate the anti-allergic effects of NBIF on IgE/Ag-induced mouse bone marrow-derived mast cells and ovalbumin-induced asthma, and the passive systemic anaphylaxis (PSA) reaction in mice. Our results showed that NBIF suppresses the production of leukotriene C4, prostaglandin D2 and inflammatory cytokines, and decreases the degranulation of BMMCs stimulated by IgE/Ag. A thorough investigation ascertained that NBIF suppresses the phosphorylation of mitogen-activated protein kinases, and represses the nuclear factor-κB-related signaling pathway. In addition, the oral administration of NBIF in mice inhibited the IgE-induced PSA reaction in a dose-dependent manner. Overall, we provide new insights into how NBIF regulates the IgE/Ag-mediated signaling pathways. Moreover, our investigation promotes the potential use of NBIF in treating allergy and asthma.

Non-oxidative pentose phosphate pathway controls regulatory T cell function by integrating metabolism and epigenetics.

Regulatory T (Treg) cells are critical for maintaining immune homeostasis and preventing autoimmunity. Here, we show that the non-oxidative pentose phosphate pathway (PPP) regulates Treg function to prevent autoimmunity. Deletion of transketolase (TKT), an indispensable enzyme of non-oxidative PPP, in Treg cells causes a fatal autoimmune disease in mice, with impaired Treg suppressive capability despite regular Treg numbers and normal Foxp3 expression levels. Mechanistically, reduced glycolysis and enhanced oxidative stress induced by TKT deficiency triggers excessive fatty acid and amino acid catabolism, resulting in uncontrolled oxidative phosphorylation and impaired mitochondrial fitness. Reduced α-KG levels as a result of reductive TCA cycle activity leads to DNA hypermethylation, thereby limiting functional gene expression and suppressive activity of TKT-deficient Treg cells. We also find that TKT levels are frequently downregulated in Treg cells of people with autoimmune disorders. Our study identifies the non-oxidative PPP as an integrator of metabolic and epigenetic processes that control Treg function.

An Automated Room Temperature Flip-Chip Mounting Process for Hybrid Printed Electronics.

Printing technology and mounting technology enable the novel field of hybrid printed electronics. To establish a hybrid printed system, one challenge is that the applied mounting process meets the requirements of functional inks and substrates. One of the most common requirements is low process temperature. Many functional inks and substrates cannot withstand the high temperatures required by traditional mounting processes. In this work, a standardized interconnection and an automated bump-less flip-chip mounting process using a room temperature curing conductive adhesive are realised. With the proposed process, the conductive adhesive selected for the standardized interconnection can be dispensed uniformly, despite its increase of viscosity already during pot time. Electrical and mechanical performance of the interconnection are characterized by four terminal resistance measurement and shear test. The herein proposed automated process allows for fabrication of hybrid printed devices in larger batch sizes than manual assembly processes used beforehand and thus, more comprehensive evaluation of device parameters. This is successfully demonstrated in a first application, a novel hybrid printed security device. The room temperature mounting process eliminates any potentially damaging thermal influence on the performance of the printed circuits that might result from other assembly techniques like soldering.

Comparison of Self-Report Questionnaire and Eye Tracking Method in the Visual Preference Study of a Youth-Beverage Model.

This study compares the characteristics of a self-report questionnaire (SRQ) and eye tracking (ET) based on a simple human-beverage visual cognition model. The young participants were mainly defined by their gender and body mass index (BMI). The beverage samples consisted of milk, coffee, cup, and coaster. SRQs allow the participants to clearly express their overall cognition of the samples in the form of vocabulary, while ET captures their hidden thinking process. The analysis, using a random forest (RF) classifier, found that participant parameters (gender and BMI) played a more important role for SRQ, while ET was related to beverage parameters (color and shape). This work reiterates that these two methods have their advantages and complement each other in food sensory analysis.