Amplifying STING Activation and Alleviating Immunosuppression through a Mn2+-Based Metal-Organic Framework Nanosystem for Synergistic Cancer Therapy.

The field of immunotherapy, particularly immune checkpoint blockade (ICB), holds immense potential in mitigating the progression of cancer. However, the challenges of insufficient tumor antigen production and the immunosuppressive state in the tumor microenvironment substantially impede patients from deriving benefits. In this research, we present a tumor-microenvironment-modulation manganese-based nanosystem, PEG-MnMOF@PTX, aiming to improve the responsiveness of ICB. Under acidic conditions, the released Mn2+ accomplishes multiple objectives. It generates toxic hydroxyl radicals (•OH), together with the released paclitaxel (PTX), inducing immunogenic cell death of tumor cells and normalizing tumor blood vessels. Concurrently, it facilitates the in situ generation of oxygen (O2) from hydrogen peroxide (H2O2), ameliorating the microenvironmental immunosuppression and increasing the efficacy of immunotherapy. In addition, this study demonstrates that PEG-MnMOF@PTX can promote the maturation of dendritic cells and augment the infiltration of cytotoxic T lymphocytes through activation of the cyclic guanosine 5'-monophosphate-adenosine 5'-monophosphate synthase (cGAS) and interferon gene stimulator (STING) pathways, namely cGAS-STING pathways, thereby heightening the sensitivity to ICB immunotherapy. The findings of this study present a novel paradigm for the progress in cancer immunotherapy.

Rapid quality evaluation and geographical origin recognition of ginger powder by portable NIRS in tandem with chemometrics.

Ginger powder is an important spice that is susceptible to improper sales such as adulteration or geographical fraud. In this study, a portable near infrared spectroscopy was used to quantitatively predict the 6-gingerol content, an important quality index of ginger, as well as to identify the gingers from three origins in China. Specifically, the optimal preprocessing method was first investigated by comparing the predictions of models. Then three feature variable selection methods including PCA, CARS, and RFrog, on the quantitative analysis of 6-gingerol were also compared, respectively. After comparison, the PLS model established on the S-G combined with SNV preprocessing outperformed the others. The PLS regression of 6-gingerol with variables selected by RFrog possessed the Rc2 of 0.9463, Rp2 of 0.9497, and the RPD of 4.2257, respectively. Moreover, the results further verified that the LDA model by SPA variables extraction successfully identify gingers from different origins with 100 % accuracy.

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.

Microbubbles-assisted ultrasonication to promote tumor accumulation of therapeutics and modulation of tumor microenvironment for enhanced cancer treatments.

Abnormal tumor vasculature is reported to severely hinder the therapeutic potency of diverse cancer therapeutics by restricting their intratumoral accumulation and/or causing therapeutic resistance. Herein, a microbubble-assisted ultrasonication technology (MAUT) of systemic administration of octafluoropropane-filled microbubbles together with tumor localized ultrasound (US) exposure is developed to generally promote intratumoral accumulation efficacy of three kinds of anti-tumor drugs with varying sizes through the cavitation effect-induced disruption of tumor blood vessels. MAUT was further shown to enable selective tumor hypoxia attenuation by filling microbubbles with high-purity oxygen and thus reducing the production of immunosuppressive lactic acids by suppressing glycolysis in cancer cells. Resultantly, MAUT markedly enhanced the therapeutic outcome of systemically administered anti-programmed death-1 (anti-PD-1) and chemotherapeutic doxorubicin (DOX) with and without using nanoscale liposomes as delivery vehicles. This work highlights that MAUT is a biocompatible yet versatile strategy to effectively reinforce the therapeutic potency of a broad range of cancer therapeutics, promising for future clinical usage.

Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironment.

BACKGROUND: Although programmed cell death protein 1 (PD-1)/ programmed cell death-ligand protein 1 (PD-L1) checkpoint blockade immunotherapy demonstrates great promise in cancer treatment, poor infiltration of T cells resulted from tumor immunosuppressive microenvironment (TIME) and insufficient accumulation of anti-PD-L1 (αPD-L1) in tumor sites diminish the immune response. Herein, we reported a drug-loaded microbubble delivery system to overcome these obstacles and enhance PD-L1 blockade immunotherapy. METHODS: Docetaxel (DTX) and imiquimod (R837)-loaded microbubbles (RD@MBs) were synthesized via a typical rotary evaporation method combined with mechanical oscillation. The targeted release of drugs was achieved by using the directional "bursting" capability of ultrasound-targeted microbubble destruction (UTMD) technology. The antitumor immune response by RD@MBs combining αPD-L1 were evaluated on 4T1 and CT26 tumor models. RESULTS: The dying tumor cells induced by DTX release tumor-associated antigens (TAAs), together with R837, promoted the activation, proliferation and recruitment of T cells. Besides, UTMD technology and DTX enhanced the accumulation of αPD-L1 in tumor sites. Moreover, RD@MBs remolded TIME, including the polarization of M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, and reduction of myeloid-derived suppressor cells (MDSCs). The RD@MBs + αPD-L1 synergistic therapy not only effectively inhibited the growth of primary tumors, but also significantly inhibited the mimic distant tumors as well as lung metastases. CONCLUSION: PD-L1 blockade immunotherapy was enhanced by RD@MBs delivery system.

Oxygen-carrying nanoplatform to reprogram tumor immunosuppressive microenvironment and enhance photothermal-immunotherapy.

Immunotherapy shows great promise on treating tumors. However, insufficient antigen exposure and immunosuppressive tumor microenvironment (TME) caused by hypoxia impose a serial of constraints on the therapeutic efficacy. In this study, we developed an oxygen-carrying nanoplatform loaded with perfluorooctyl bromide (PFOB, a second-generation of perfluorocarbon-based blood substitute), IR780 (a photosensitizer) and imiquimod (R837, an immune adjuvant) to reprogram immunosuppressive TME and reinforce photothermal-immunotherapy. The obtained oxygen-carrying nanoplatforms (abbreviated as IR-R@LIP/PFOB) show highly efficient oxygen release behavior and excellent hyperthermia performance upon laser irradiation, thus achieving the attenuation of the inherent tumor hypoxia and the exposure of tumor associated antigens in situ, and transforming the immunosuppressive TME to an immunosupportive one. We found that the photothermal therapy of IR-R@LIP/PFOB together with anti-programmed cell death protein-1 (anti-PD-1) would elicit a robust antitumor immunity by increasing the tumor-infiltrating frequencies of cytotoxic CD8+ T cells and tumoricidal M1-phenotype macrophages, while reducing immunosuppressive M2-phenotype macrophages and regulatory T cells (Tregs). This study presents these oxygen-carrying IR-R@LIP/PFOB nanoplatforms are potent in removing some negative impacts of immunosuppressive TME caused by hypoxia, and suppressing tumor growth by initiating antitumor immune responses, especially in combination with anti-PD-1 immunotherapy.

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.

Zinc homeostasis and regulation: Zinc transmembrane transport through transporters.

The second abundant micronutrient, zinc, is attracting more and more attention for it performs essential functions in living organisms and bears close relationships with the occurrence of diseases. However, excess zinc is toxic to cells. Ensuring a balanced zinc state for organisms is essential. Zinc transporters, including ZIPs and ZnTs, are pivotal in regulating zinc homeostasis. Benefiting from zinc transporter structures determination and their transporting dynamic revelation, the clarification of detailed mechanisms of zinc trafficking and the maintenance of zinc homeostasis by transporters in the human body are getting more and more evident. The present review gives a detailed description of the structural basis of zinc transport through ZIP and ZnT, through which the molecular mechanism of zinc binding and transport was illustrated. Then the motive force that drives zinc transmembrane transport and finally a generalization for the regulation models of zinc transporters were summarized.

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.

Directed Self-Assembly of Dimeric Building Blocks into Networklike Protein Origami to Construct Hydrogels.

Engineering proteins to construct self-assemblies is of crucial significance not only for understanding the sophisticated living systems but also for fabricating advanced materials with unexplored functions. However, due to the inherent chemical heterogeneity and structural complexity of the protein surface, designing complex protein assemblies in an anisotropic fashion remains challenging. Here, we describe a self-assembly approach to fabricating protein origami with a networklike structure by designing dual noncovalent interactions on the different positions of a single protein building block. With dimeric proteins as building blocks, 1D protein filaments were constructed by the designed metal coordination at key protein interfaces. Subsequently, the network superstructures were created by the cross-linking of the 1D protein filaments at branch point linkages through the second designed π-π stacking interactions. Notably, upon increasing the protein concentration, the formed protein networks convert into hydrogels with reversible, injectable, and self-healing properties, which have the ability to promote bone regeneration. This strategy could be used to fabricate other protein-based materials with unexplored functions.

Embryonic exposure to selenium nanoparticles delays growth and hatching in the freshwater snail Lymnaea stagnalis.

Selenium nanoparticles (SeNPs) have been applied in the biomedical and biocidal domain which may have potential environmental risks for aquatic systems. However, the knowledge of its toxicity and the role of functionalization on aquatic invertebrates are scarce. Thus, the present study aimed to analyze the embryotoxicity of two types of SeNPs coated with Sodium carboxymethyl cellulose (CMC-SeNPs) and Chitosan (CS-SeNPs) to the freshwater snail Lymnaea stagnalis in lake water, focusing on embryonic development. The influence of surface coatings and ions release, on the embryonic development of SeNPs to freshwater snail L. stagnalis was investigated. For this end, the snails were exposed to different concentrations of SeNPs and Se ions (0.05-1 mg L-1) during 7 days and multiple endpoints were analyzed, including developmental stage frequency, morphological alterations, embryos mortality and hatching success. The results showed that both Se forms promoted the developmental delay, mortality, morphological changes, and hatching inhibition in snail embryos in a concentration-dependent manner. CMC-SeNPs are 2.6 times more embryotoxic compared to CS-SeNPs indicating the importance of surface coating on the embryotoxicity. Moreover, the results revealed that although both forms of Se inhibited the embryo development and reduced the hatching of L. stagnalis, the mode of action on the embryogenesis was different. SeNPs had a higher toxicity to snails' embryos compared to their dissolved counterparts. Despite significant dissolution, by comparing the SeNPs with their dissolved fraction, the results suggest SeNPs inhibition effect on the snail development could be caused by both SeNPs and Se4+, and SeNPs might be the major development retardation driver rather than Se ions. The present study evidenced by the first time the toxicity effects of SeNPs on the snail embryogenesis, and highlighted how SeNPs intrinsic properties influence their transformation and toxicity in environmental relevant scenarios.

Bio-based antibacterial food packaging films and coatings containing cinnamaldehyde: A review.

As a typical bioactive compound from the bark and leaves of the trees of the genus Cinnamomum, cinnamaldehyde (CIN) is natural and safe. Its excellent antibacterial activity against various foodborne microorganisms is growingly regarded as a promising additive for improving and enhancing the properties of bio-based packaging films/coatings. This review systematically summarized the bio-based food packaging films/coatings containing CIN developed recently. The effects of CIN incorporation on physical and chemical properties of the antibacterial food packaging films/coatings, including thickness, color index, transparency, water content, water solubility, water contact angle, mechanical performances, water barrier performances, and antibacterial performances, were discussed. Simultaneously, this work also concluded that an explanation of the antibacterial mechanism of CIN and preparation methods of bio-based packaging films/coatings containing CIN/CIN carriers. Notably, the incorporation of CIN into the films/coatings could enhance their antibacterial performance extend the shelf-life of various foods, such as fish, meats, vegetables, fruits, and other perishable food, while improving their physical and chemical properties. Although incorporating CIN into food packaging films/coatings has been extensively studied, long-term follow-up research on the human safety of active food packaging films/coatings containing CIN needs to be carried out.

A short helix regulates conversion of dimeric and 24-meric ferritin architectures.

The inter-subunit interaction at the protein interfaces plays a key role in protein self-assembly, through which enabling protein self-assembly controllable is of great importance for preparing the novel nanoscale protein materials with unexplored properties. Different from normal 24-meric ferritin, archaeal ferritin, Thermotoga maritima ferritin (TmFtn) naturally occurs as a dimer, which can assemble into a 24-mer nanocage induced by salts. However, the regulation mechanism of protein self-assembly underlying this phenomenon remains unclear. Here, a combination of the computational energy simulation and key interface reconstruction revealed that a short helix involved interactions at the C4 interface are mainly responsible for the existence of such dimer. Agreeing with this idea, deletion of such short helix of each subunit triggers it to be a stable dimer, which losses the ability to reassemble into 24-meric ferritin in the presence of salts in solution. Further support for this idea comes from the observation that grafting a small helix from human H ferritin onto archaeal subunit resulted in a stable 24-mer protein nanocage even in the absence of salts. Thus, these findings demonstrate that adjusting the interactions at the protein interfaces appears to be a facile, effective approach to control subunit assembly into different protein architectures.

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.

Stability and surface properties of selenium nanoparticles coated with chitosan and sodium carboxymethyl cellulose.

The effect of polysaccharide coatings on the stability and release characteristics of selenium nanoparticles (SeNPs) was evaluated by comparing the characteristics of chitosan-coated SeNPs (CS-SeNPs) and sodium carboxymethyl cellulose-coated SeNPs (CMC-SeNPs). The release characteristics of SeNPs were investigated in storage conditions, gastrointestinal conditions, and free radical systems. CMC-SeNPs formed dimers or trimers, whereas CS-SeNPs were monodispersed but formed large aggregates in a pH range of 7.4-8.25. Upon 50 days of storage at 30 °C, both CMC-SeNPs and CS-SeNPs were converted to Se4+. SeNPs exhibited a lower release rate in simulated gastrointestinal conditions than in free radical systems. SeNPs release in ABTS and superoxide anion free radical systems followed the first-order and Korsmeyer-Peppas models, respectively, indicating that SeNP release is mainly governed by dissolution mechanisms. Additional studies are needed to examine the potential environmental effects and biological activity of the Se4+ released from SeNPs.

Toxicity of selenium nanoparticles on Poterioochromonas malhamensis algae in Waris-H culture medium and Lake Geneva water: Effect of nanoparticle coating, dissolution, and aggregation.

Understanding the algal toxicity of selenium nanoparticles (SeNPs) in aquatic systems by considering SeNPs physicochemical properties and environmental media characteristics is a concern of high importance for the evaluation and prediction of risk assessment. In this study, chitosan (CS) and sodium carboxymethyl cellulose (CMC) coated SeNPs are considered using Lake Geneva water and a Waris-H cell culture medium to investigate the effect of SeNPs on the toxicity of algae Poterioochromonas malhamensis, a widespread mixotrophic flagellate. The influence of surface coating, z-average diameters, ζ-potentials, aggregation behavior, ions release, and medium properties on the toxicity of SeNPs to algae P. malhamensi was investigated. It is found that SeNPs are 5-10 times more toxic in Lake Geneva water compared to the culture medium, suggesting that the traditional algal tests in Waris-H culture medium currently underestimate the toxicity of NPs in a natural water environment. Despite significant dissolution, it is also found that SeNPs themselves are the toxicity driver, and dissolved ions have only a marginal influence on toxicity. SeNPs diameter is found a minor factor in toxicity. Based on a principal component analysis (PCA) it is found that in Lake Geneva water, the nature of the surface coating (CMC versus CS) is the most influential factor controlling the toxicity of SeNPs. In the culture medium, surface coating, ζ-potential, and aggregation are found to contribute at the same level. These results highlight the importance of considering in details both NPs intrinsic and media properties in the evaluation of NPs biological effects.

Physicochemical stability and functional properties of selenium nanoparticles stabilized by chitosan, carrageenan, and gum Arabic.

To meet the increasing demand for polysaccharide-stabilized selenium nanoparticles (PS-Se°NPs) for industrial applications, in this study, we employed three commonly-used polysaccharides (i.e. chitosan (CS), carrageenan (Cg) and Gum Arabic (GA)) to fabricate Se°NPs, and compared their functional properties and their physicochemical stabilities, under varying conditions (ionic strength, pH, and temperature). The results showed that CS-Se°NPs had higher storage stability but easily aggregated in 500 mM NaCl or at pH > 8 because of their surface cationic groups. This, however, improved their DPPH free radical scavenging and antitumor activities. Compared to CS-Se°NPs, the anionic groups in Cg-Se°NPs increased their resistant to pH variations and reduced cellular toxicity, and the multi-branched structure of GA-Se°NPs increased their thermal stability. Overall, this study shows that the behaviors of PS-Se°NPs depends mainly on ionizable functional groups and the structure of polysaccharides, contributing to the development of PS-Se°NPs with applicability in the food and pharmaceutical industries.

Hippuric Acid Promotes Renal Fibrosis by Disrupting Redox Homeostasis via Facilitation of NRF2-KEAP1-CUL3 Interactions in Chronic Kidney Disease.

Chronic kidney disease (CKD) is characterized by the accumulation of protein-bound uremic toxins (PBUTs), which play a pathophysiological role in renal fibrosis (a common pathological process resulting in CKD progression). Accumulation of the PBUT hippuric acid (HA) is positively correlated with disease progression in CKD patients, suggesting that HA may promote renal fibrosis. Oxidative stress is the most important factor affecting PBUTs nephrotoxicity. Herein, we assessed the ability of HA to promote kidney fibrosis by disrupting redox homeostasis. In HK-2 cells, HA increased fibrosis-related gene expression, extracellular matrix imbalance, and oxidative stress. Additionally, reactive oxygen species (ROS)-mediated TGFß/SMAD signaling contributed to HA-induced fibrotic responses. HA disrupted antioxidant networks by decreasing the levels of nuclear factor erythroid 2-related factor 2 (NRF2), leading to ROS accumulation and fibrotic responses, as evidenced by NRF2 activation and knockdown. Moreover, NRF2 levels were reduced by NRF2 ubiquitination, which was regulated via increased interactions of Kelch-like ECH-associated protein 1 with Cullin 3 and NRF2. Finally, renal fibrosis and redox imbalance promoted by HA were confirmed in rats. Importantly, sulforaphane (NRF2 activator) reversed HA-promoted renal fibrosis. Thus, HA promotes renal fibrosis in CKD by disrupting NRF2-driven antioxidant system, indicating that NRF2 is a potential therapeutic target for CKD.

Physicochemical and functional properties of chitosan-stabilized selenium nanoparticles under different processing treatments.

Selenium nanoparticles (Se0NPs) have been well-characterized; however, whether processing affects their physicochemical and functional properties remains unknown. Here, chitosan (low and high molecular weight; CS(L) and CS(H), respectively) was used to stabilize Se0NPs, and the effects of heating (37 â„ƒ, 70 â„ƒ, and 95 â„ƒ), freeze-drying-rehydration, and freeze-thawing on CS-Se0NPs physicochemical stability, Se release, antioxidant capacity, and antibacterial activity were evaluated. The results demonstrated that all treatments could cause CS-Se0NPs aggregation and Se release to varying degrees. Aggregation of CS-Se0NPs decreased their antibacterial activity, while Se release increased their antioxidant capacity with negligible effects on antibacterial activities. None of the CS-Se0NPs could tolerate freeze-thawing. CS(H)-Se0NPs exhibited better rehydration and heating stability than CS(L)-Se0NPs, although "rod-like" triclinic crystalline Se in CS(H)-Se0NPs, produced by 95℃ heating, decreased both antioxidant and antibacterial activities. Thus, these results provide a theoretical basis for the development and suitable application of CS-Se0NPs.

Effect of molecular weight of chitosan and its oligosaccharides on antitumor activities of chitosan-selenium nanoparticles.

The antitumor activity of zero-valent selenium (Se0) nanoparticles stabilized by chitosan and its oligosaccharides having molecular weights 3 k, 65 k, and 600 k Da, was investigated. The nanoparticles stabilized with high molecular weight chitosan not only released selenium more easily compared with low molecular weight chitosan, but were also taken up by HepG2 cells more easily through electrostatic effect. Moreover, these were more efficient in inhibiting HepG2 cell viability. High ROS levels of cancer cells could easily induce selenium release from these nanoparticles, and oxidize the less toxic Se0 to highly toxic Se4+. The latter could not only consume antioxidant enzymes, but also cause mitochondrial dysfunction and cell apoptosis. Study of antitumor efficacy and side effect on a HepG2 xenograft BALB/c nude mice model exhibited that CS-Se0NPs had a higher selectivity for cancer cells; however, their effect on normal cells, which have relatively lower ROS levels, was limited.