Fabrication of polysaccharide-coated oleanolic acid-curcumin-coassembled nanoparticles (OA/Cur NPs): Enhancement of colloidal stability and water solubility.

Natural terpenoid carriers, such as oleanolic acid (OA), can enhance the water solubility and stability of hydrophobic compounds such as curcumin (Cur). However, improving the colloidal stability of nanoparticle emulsions and resolving the redispersion problem of freeze-dried nanoparticle powders remain significant challenges. In this study, we fabricated coassembled oleanolic acid-curcumin nanoparticles (OA/Cur NPs) and applied a polysaccharide surface coating method to improve their colloidal stability and water solubility. The results showed that the optimal ratio of Cur/OA for preparing OA/Cur NPs was 4:10, resulting in a high encapsulation efficiency (EE) of Cur (75.2%). Additionally, TEM, contact angle tests, Turbiscan TOWER optical stability analysis of the polysaccharide-coated OA/Cur NP emulsions and redispersion tests of their lyophilized powders verified the advantages of carboxymethyl chitosan/ß-cyclodextrin (CMC/ß-CD) coating over other polysaccharides. This study indicated that polysaccharide coating is an effective method for enhancing the colloidal stability, water solubility, and redispersibility of OA/Cur NPs.

Current role of magnetic resonance imaging on assessing and monitoring the efficacy of phototherapy.

Phototherapy, also known as photobiological therapy, is a non-invasive and highly effective physical treatment method. Its broad use in clinics has led to significant therapeutic results. Phototherapy parameters, such as intensity, wavelength, and duration, can be adjusted to create specific therapeutic effects for various medical conditions. Meanwhile, Magnetic Resonance Imaging (MRI), with its diverse imaging sequences and excellent soft-tissue contrast, provides a valuable tool to understand the therapeutic effects and mechanisms of phototherapy. This review explores the clinical applications of commonly used phototherapy techniques, gives a brief overview of how phototherapy impacts different diseases, and examines MRI's role in various phototherapeutic scenarios. We argue that MRI is crucial for precise targeting, treatment monitoring, and prognosis assessment in phototherapy. Future research and applications will focus on personalized diagnosis and monitoring of phototherapy, expanding its applications in treatment and exploring multimodal imaging technology to enhance diagnostic and therapeutic precision and effectiveness.

Chelation-directed interface engineering of in-place self-cleaning membranes.

Water-energy sustainability will depend upon the rapid development of advanced pressure-driven separation membranes. Although energy-efficient, water-treatment membranes are constrained by ubiquitous fouling, which may be alleviated by engineering self-cleaning membrane interfaces. In this study, a metal-polyphenol network was designed to direct the armorization of catalytic nanofilms (ca. 18 nm) on inert polymeric membranes. The chelation-directed mineralized coating exhibits high polarity, superhydrophilicity, and ultralow adhesion to crude oil, enabling cyclable crude oil-in-water emulsion separation. The in-place flux recovery rate exceeded 99.9%, alleviating the need for traditional ex situ cleaning. The chelation-directed nanoarmored membrane exhibited 48-fold and 6.8-fold figures of merit for in-place self-cleaning regeneration compared to the control membrane and simple hydraulic cleaning, respectively. Precursor interaction mechanisms were identified by density functional theory calculations. Chelation-directed armorization offers promise for sustainable applications in catalysis, biomedicine, environmental remediation, and beyond.

Breast Cancer Stem Cells Secrete MIF to Mediate Tumor Metabolic Reprogramming That Drives Immune Evasion.

Reprogramming of energy metabolism exerts pivotal functions in cancer progression and immune surveillance. Identification of the mechanisms mediating metabolic changes in cancer may lead to improved strategies to suppress tumor growth and stimulate antitumor immunity. Here, it was observed that the secretomes of hypoxic breast cancer cells and breast cancer stem cells (BCSC) induced reprogramming of metabolic pathways, particularly glycolysis, in normoxic breast cancer cells. Screening of the BCSC secretome identified MIF as a pivotal factor potentiating glycolysis. Mechanistically, MIF increased c-MYC-mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/ß-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Consequently, targeting MIF improved the therapeutic efficacy of immune checkpoint blockade in triple-negative breast cancer. Collectively, this study proposes MIF as an attractive therapeutic target to circumvent metabolic reprogramming and immunosuppression in breast cancer. SIGNIFICANCE: MIF secreted by breast cancer stem cells induces metabolic reprogramming in bulk tumor cells and engenders an immunosuppressive microenvironment, identifying MIF targeting as a strategy to improve immunotherapy efficacy in breast cancer.

Improving astaxanthin-loaded chitosan/polyvinyl alcohol/graphene oxide nanofiber membranes and their application in periodontitis.

Periodontitis is a chronic inflammatory disease primarily driven by host inflammation and plaque-induced immune responses. Controlling the host inflammatory response and improving the periodontal inflammatory microenvironment are crucial to promoting periodontal tissue regeneration. In this study, the blended nanofiber membranes previously prepared by our research group were improved, and we developed multifunctional chitosan/polyvinyl alcohol/graphene oxide/astaxanthin coaxial nanofiber membranes. Scanning electron microscopy showed that the prepared nanofibers had a smooth surface and a uniform diameter distribution. The mechanical property test results showed that the coaxial nanofiber membranes exhibited higher tensile strength compared to the blended nanofiber membranes, which increased from 4.50 ± 0.32 and 3.70 ± 0.45 MPa to 7.12 ± 0.22 and 5.62 ± 0.79 MPa respectively. Drug release studies indicated that the "shell-core" structure of coaxial nanofibers significantly reduced the initial burst release of astaxanthin (ASTA), with only 13.49 % and 10.71 % release in the first 24 h, and drug release lasted for over a week. Animal experiments confirmed that the coaxial nanofiber membranes loaded with ASTA promoted periodontal bone defect repair while inhibiting periodontal inflammation. In conclusion, the prepared coaxial nanofiber membranes are a promising sustained-release drug system for treating periodontitis.

Acute stress selectively blunts reward anticipation but not consumption: An ERP study.

Stress-induced dysfunction of reward processing is documented to be a critical factor associated with mental illness. Although many studies have attempted to clarify the relationship between stress and reward, few studies have investigated the effect of acute stress on the temporal dynamics of reward processing. The present study applied event-related potentials (ERP) to examine how acute stress differently influences reward anticipation and consumption. In this study, seventy-eight undergraduates completed a two-door reward task following a Trier Social Stress Task (TSST) or a placebo task. The TSST group showed higher cortisol levels, perceived stress, anxiety, and negative affect than the control group. For the control group, a higher magnitude of reward elicited a reduced cue-N2 but increased stimulus-preceding negativity (SPN), suggesting that controls were sensitive to reward magnitude. In contrast, these effects were absent in the stress group, suggesting that acute stress reduces sensitivity to reward magnitude during the anticipatory phase. However, the reward positivity (RewP) and P3 of both groups showed similar patterns, which suggests that acute stress has no impact on reward responsiveness during the consummatory phase. These findings suggest that acute stress selectively blunts sensitivity to reward magnitude during the anticipatory rather than the consummatory phase.

Engineering In Situ Catalytic Cleaning Membrane Via Prebiotic-Chemistry-Inspired Mineralization.

Pressure-driven membrane separation promises a sustainable energy-water nexus but is hindered by ubiquitous fouling. Natural systems evolved from prebiotic chemistry offer a glimpse of creative solutions. Herein, a prebiotic-chemistry-inspired aminomalononitrile (AMN)/Mn2+ -mediated mineralization method is reported for universally engineering a superhydrophilic hierarchical MnO2 nanocoating to endow hydrophobic polymeric membranes with exceptional catalytic cleaning ability. Green hydrogen peroxide catalytically triggered in-situ cleaning of the mineralized membrane and enabled operando flux recovery to reach 99.8%. The mineralized membrane exhibited a 9-fold higher recovery compared to the unmineralized membrane, which is attributed to active catalytic antifouling coupled with passive hydration antifouling. Electron density differences derived from the precursor interaction during mediated mineralization unveiled an electron-rich bell-like structure with an inner electron-deficient Mn core. This work paves the way to construct multifunctional engineered materials for energy-efficient water treatment as well as for diverse promising applications in catalysis, solar steam generation, biomedicine, and beyond.

The Extraction, Characterization and Biological Activity of Natural Products.

The aim of this Special Issue, entitled "The Extraction, Characterization and Biological Activity of Natural Products", is to expand our knowledge and promote a better understanding of the latest scientific advances in the field of the extraction, isolation and characterization of biologically active compounds of natural plants [...].

The role of toll-like receptors in immune tolerance induced by Helicobacter pylori infection.

Helicobacter pylori (H. pylori) is a gram-negative, microaerobic bacterium that colonizes the gastric mucosa in about half of the world's population. H. pylori infection can lead to various diseases. Chronic infection by H. pylori exposes the gastric mucosa to bacterial components such as lipopolysaccharide (LPS), outer membrane vesicles (OMVs), and several toxic proteins. Infected with H. pylori activates the release of pro-inflammatory factors and triggers inflammatory responses that damage the gastric mucosa. As the only microorganism that permanently colonizes the human stomach, H. pylori can suppress host immunity to achieve long-term colonization. Toll-like receptors (TLRs) play a crucial role in T-cell activation, promoting innate immune responses and immune tolerance during H. pylori infection. Among the 10 TLRs found in humans, TLR2, TLR4, TLR5, and TLR9 have been thoroughly investigated in relation to H. pylori-linked immune regulation. In the present review, we provide a comprehensive analysis of the various mechanisms employed by different TLRs in the induction of immune tolerance upon H. pylori infection, which will contribute to the research of pathogenic mechanism of H. pylori.

Biodegradable electrospinning superhydrophilic nanofiber membranes for ultrafast oil-water separation.

Although membrane technology has attracted considerable attention for oily wastewater treatment, the plastic waste generated from discarded membranes presents an immediate challenge for achieving eco-friendly separation. We designed on-demand biodegradable superhydrophilic membranes composed of polylactic acid nanofibers in conjunction with polyethylene oxide hydrogels using electrospinning technology for ultrafast purification of oily water. Our results showed that the use of the polyethylene oxide hydrogels increased the number of hydrogen bonds formed between the membrane surface and water molecules by 357.6%. This converted hydrophobic membranes into superhydrophilic ones, which prevented membrane fouling and accelerated emulsion penetration through the membranes. The oil-in-water emulsion permeance of our newly designed nanofiber membranes increased by 61.9 times (2.1 × 104 liters per square meter per hour per bar) with separation efficiency >99.6%, which was superior to state-of-the-art membranes. Moreover, the formation of hydrogen bonds was found to accelerate polylactic acid biodegradation into lactic acid by over 30%, offering a promising approach for waste membrane treatment.

Comprehensive characterization of tumor microenvironment in colorectal cancer via molecular analysis.

Colorectal cancer (CRC) remains a challenging and deadly disease with high tumor microenvironment (TME) heterogeneity. Using an integrative multi-omics analysis and artificial intelligence-enabled spatial analysis of whole-slide images, we performed a comprehensive characterization of TME in colorectal cancer (CCCRC). CRC samples were classified into four CCCRC subtypes with distinct TME features, namely, C1 as the proliferative subtype with low immunogenicity; C2 as the immunosuppressed subtype with the terminally exhausted immune characteristics; C3 as the immune-excluded subtype with the distinct upregulation of stromal components and a lack of T cell infiltration in the tumor core; and C4 as the immunomodulatory subtype with the remarkable upregulation of anti-tumor immune components. The four CCCRC subtypes had distinct histopathologic and molecular characteristics, therapeutic efficacy, and prognosis. We found that the C1 subtype may be suitable for chemotherapy and cetuximab, the C2 subtype may benefit from a combination of chemotherapy and bevacizumab, the C3 subtype has increased sensitivity to the WNT pathway inhibitor WIKI4, and the C4 subtype is a potential candidate for immune checkpoint blockade treatment. Importantly, we established a simple gene classifier for accurate identification of each CCCRC subtype. Collectively our integrative analysis ultimately established a holistic framework to thoroughly dissect the TME of CRC, and the CCCRC classification system with high biological interpretability may contribute to biomarker discovery and future clinical trial design.

New Biological and Chemical Insights into Optimization of Chamomile Extracts by Using Artificial Neural Network (ANN) Model.

Chamomile is one of the most consumed medicinal plants worldwide. Various chamomile preparations are widely used in various branches of both traditional and modern pharmacy. However, in order to obtain an extract with a high content of the desired components, it is necessary to optimize key extraction parameters. In the present study, optimization of process parameters was performed using the artificial neural networks (ANN) model using a solid-to-solvent ratio, microwave power and time as inputs, while the outputs were the yield of the total phenolic compounds (TPC). Optimized extraction conditions were as follows: a solid-to-solvent ratio of 1:80, microwave power of 400 W, extraction time of 30 min. ANN predicted the content of the total phenolic compounds, which was later experimentally confirmed. The extract obtained under optimal conditions was characterized by rich composition and high biological activity. Additionally, chamomile extract showed promising properties as growth media for probiotics. The study could make a valuable scientific contribution to the application of modern statistical designs and modelling to improve extraction techniques.

Paracrine secretion of IL8 by breast cancer stem cells promotes therapeutic resistance and metastasis of the bulk tumor cells.

BACKGROUND: Breast tumors consist of heterogeneous cellular subpopulations that differ in molecular properties and functional attributes. Cancer stem cells (CSCs) play pivotal roles in cancer therapeutic failure and metastasis. However, it remains indeterminate how CSCs determine the progression of the bulk cancer cell population. METHODS: Co-culture systems in vitro and co-implantation systems in vivo were designed to characterize the interactions between breast cancer stem cells (BCSCs) and bulk cancer cells. RNA sequencing was performed to study the functional and mechanistic implications of the BCSC secretome on bulk cancer cells. A cytokine antibody array was employed to screen the differentially secreted cytokines in the BCSC secretome. Tail vein injection metastatic models and orthotopic xenograft models were applied to study the therapeutic potential of targeting IL8. RESULTS: We identified that the BCSC secretome potentiated estrogen receptor (ER) activity in the bulk cancer cell population. The BCSC secretome rendered the bulk cancer cell population resistant to anti-estrogen and CDK4/6 inhibitor therapy; as well as increased the metastatic burden attributable to bulk cancer cells. Screening of the BCSC secretome identified IL8 as a pivotal factor that potentiated ERα activity, endowed tamoxifen resistance and enhanced metastatic burden by regulation of bulk cancer cell behavior. Pharmacological inhibition of IL8 increased the efficacy of fulvestrant and/or palbociclib by reversing tamoxifen resistance and abrogated metastatic burden. CONCLUSION: Taken together, this study delineates the mechanism by which BCSCs determine the therapeutic response and metastasis of bulk cancer cells; and thereby suggests potential therapeutic strategies to ameliorate breast cancer outcomes. Video Abstract.

Photo-degradable salecan/xanthan gum ionic gel induced by iron (III) coordination for organic dye decontamination.

As dye adsorbents with great potential, polysaccharide-based hydrogels are significantly hampered in practical application owing to intricate preparation methods, low absorption, and bad degradability. Salecan is a water-soluble extracellular polysaccharide with excellent physicochemical and biological properties. Here, salecan and xanthan gum were first used as a dual-precursors system, their mixed solution was crosslinked by Fe3+ to assemble a photo-degradable ionic gel for malachite green (MG) adsorption. Photo-degradation was done using visible light under very mild conditions, which gave rise to gel network dissolution and homogeneous solution formation. Extensive dynamic coordinate interactions between Fe3+ and polysaccharides maintained gel matrix stability and were systematically investigated. The control of water uptake, micro-structure, and rheology can be facilely implemented by tuning salecan/xanthan gum ratios. Furthermore, various parameters such as polysaccharide ratios, pHs, MG concentrations, and contact time affecting adsorption were optimized using batch experiments. Adsorption process accurately adhered to pseudo-second-order kinetic and Langmuir isotherm model, with the maximum adsorption capacity of 463.0 mg/g. Such mechanism implied monolayer chemisorptive characteristics. The gel exhibited satisfactory reusability and was recycled five times without apparent decrease in adsorption capacity. From these results, the photo-degradable Fe3+-induced salecan/xanthan gum ionic gel is an alternative and sustainable absorbent for MG removal.

OsCIP1, a secreted protein, binds to and stabilizes OsCR4 to promote aleurone layer development, seed germination and early seedling growth in rice.

The receptor kinase CRINKLY 4 (CR4) and its orthologs are known for their essential roles in cell differentiation and their shuttling between plasma membrane and cytoplasmic vesicles, a unique feature tied to their extracellular domain. However, the extracellular regulators of CR4 have been little known. Here we identified an OsCR4 Interacting Protein 1 (OsCIP1) (also named as OsLTPL36 in rice) by a yeast two-hybrid screen using the extracellular domain of OsCR4 (OsCR4E) as bait. OsCIP1/OsLTPL36 harbors a signal peptide and is localized to the outer surface of the plasma membrane. It interacted with the TNFR subdomain of OsCR4, causing an increase in OsCR4 recycling to the plasma membrane. oscip1, in which OsCR4 protein was decreased, exhibited thinner aleurone layer, late germination and delayed growth; while OsCIP1-overexpressing plants, in which OsCR4 protein was increased, displayed enhanced growth at the early seedling stage. OsCIP1 was cleaved between W61 and Q62, and the resulting C-terminal half exhibited a greater affinity for OsCR4E than did its precursor. Abolishing this cleavage site compromises OsCIP1's ability to promote seedling growth. Our results provide valuable clues for the regulation of CR4 activity and its functions in aleurone layer cell differentiation by a secreted small protein in rice.

Blunted reward responsiveness prospectively predicts emotional distress when exposed to a naturalistic stressor.

Both stress and blunted reward responsiveness have been identified as core risk factors of depression. Whether blunted reward responsiveness increases psychological vulnerability to real-life stress from a dynamic perspective (from stress reactivity to recovery) has not been investigated. By utilizing a real-world stressful event (i.e. the final examination), this study aimed to explore the role of reward responsiveness in the stress-emotional distress relationship during stress reactivity and recovery phases. We followed 57 undergraduates with three assessments, from six weeks before examination weeks (T1, baseline), one day before the examinations (T2) to two weeks after the examinations (T3), therefore, covering stress reactivity (T1 to T2) and recovery (T2 to T3) phases. At baseline, reward responsiveness was measured as the Reward Positivity (RewP) in the doors task. Stress and emotional distress (anxiety and depression) were reported at T1, T2 and T3 to capture their dynamic changes. Results showed that self-report stress levels significantly increased from T1 to T2 (stress reactivity phase) and decreased from T2 to T3 (stress recovery phase). Furthermore, blunted reward responsiveness at baseline prospectively predicted emotional distress during the stress reactivity phase but not the recovery phase. Specifically, during the stress reactivity phase, higher perceived stress was associated with greater anxiety and depression only in participants with relatively smaller residual RewP amplitudes but not in participants with relatively larger residual RewP amplitudes. Our study demonstrated that a blunted reward responsiveness is a vulnerable factor of depression, especially when exposed to stress. Our findings provide insights into prevention and intervention for stress-related disturbance.

CITEdb: a manually curated database of cell-cell interactions in human.

MOTIVATION: The interactions among various types of cells play critical roles in cell functions and the maintenance of the entire organism. While cell-cell interactions are traditionally revealed from experimental studies, recent developments in single-cell technologies combined with data mining methods have enabled computational prediction of cell-cell interactions, which have broadened our understanding of how cells work together, and have important implications in therapeutic interventions targeting cell-cell interactions for cancers and other diseases. Despite the importance, to our knowledge, there is no database for systematic documentation of high-quality cell-cell interactions at the cell type level, which hinders the development of computational approaches to identify cell-cell interactions. RESULTS: We develop a publicly accessible database, CITEdb (Cell-cell InTEraction database, https://citedb.cn/), which not only facilitates interactive exploration of cell-cell interactions in specific physiological contexts (e.g. a disease or an organ) but also provides a benchmark dataset to interpret and evaluate computationally derived cell-cell interactions from different tools. CITEdb contains 728 pairs of cell-cell interactions in human that are manually curated. Each interaction is equipped with structured annotations including the physiological context, the ligand-receptor pairs that mediate the interaction, etc. Our database provides a web interface to search, visualize and download cell-cell interactions. Users can search for cell-cell interactions by selecting the physiological context of interest or specific cell types involved. CITEdb is the first attempt to catalogue cell-cell interactions at the cell type level, which is beneficial to both experimental, computational and clinical studies of cell-cell interactions. AVAILABILITY AND IMPLEMENTATION: CITEdb is freely available at https://citedb.cn/ and the R package implementing benchmark is available at https://github.com/shanny01/benchmark. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.