Promoting elemental mercury immobilization performance from smelting flue gas over a wide temperature range via cobalt-doped copper sulfide adsorbents.

Copper sulfide (CuS) sorbent exhibits great potential for gaseous elemental mercury (Hg0) decontamination, but it still suffers from a narrow operating temperature. Therefore, designing advanced CuS sorbents that have a high activity level for capturing Hg0 and thermal stability at a high temperature range is challenging. Herein, we propose a metal doping strategy to fabricate a bimetallic sulfide adsorbent. Benefiting the unique structure and composition, a mesoporous structure and an abundance of unsaturated sulfur sites ensure that CuxCo(1-x)Sy provides a desirable level of adsorption for Hg0. The experimental results indicate the optimum Co doping mass concentration of 5 %. The Cu0.95Co0.05Sy not only performs satisfactory Hg0 adsorption at elevated temperatures (Hg0 average adsorption efficiency of over 97.3 %, Hg0 average adsorption rate of over 2.7 µg/g/min), but also presents an exciting regeneration and recycle performance (a Hg0 adsorption efficiency of over 94 % after 10 cycles). The adsorption capacity of Cu0.95Co0.05Sy at the breakthrough threshold of 25 % reaches 5.22 mg/g, surpassing most of metal sulfide sorbents for Hg0 immobilization at 150 °C. As far as Hg0 adsorption is concerned, the composition of typical smelting flue gases has almost no effect. According to further studies, unsaturated coordination short-chain sulfur (S22-) sites are essential for adsorption of Hg0 and are capable of directly forming α-HgS from Hg0. In both the contrast experiment and density functional theory calculations, the cobalt doping strategy enhances the thermal stability of the active S22- ligand and the Hg0 adsorption properties. This study not only provide a prospective adsorbent for Hg0 sequestration at wide temperature range, but also explores a method of utilizing gaseous contaminants for resource utilization.

Interaction of zein/HP-ß-CD nanoparticles with digestive enzymes: Enhancing curcumin bioavailability.

The low bioavailability of polyphenolic compounds due to poor solubility and stability is a major challenge. Encapsulation of polyphenols in zein-based composite nanoparticles can improve the water dispersion, stability, targeted delivery, and controlled release of polyphenols in the gastrointestinal tract. In this study, we investigated the fluorescence properties, bioactivity, and microstructural characteristics of polyphenols during digestion, revealing that zein nanoparticles protect polyphenols from gastric degradation and promote their sustained release in the small intestine. The effects of different ionic species and salt ion concentrations on the digestive properties of polyphenol complex delivery systems have also been explored. In addition, the formation of "protein corona" structures during digestion may affect bioavailability. These findings highlight the potential of nanoparticle formulations to improve polyphenol stability and absorption. The results of this study may provide new insights and references for the study of polyphenol bioavailability enhancement.

Taz/Tead1 Promotes Alternative Macrophage Activation and Kidney Fibrosis via Transcriptional Upregulation of Smad3.

Macrophage alternative activation is involved in kidney fibrosis. Previous researches have documented that the transcriptional regulators Yes-associated protein (Yap)/transcriptional coactivator with PDZ-binding motif (Taz) are linked to organ fibrosis. However, limited knowledge exists regarding the function and mechanisms of their downstream molecules in regulating macrophage activation and kidney fibrosis. In this paper, we observed that the Hippo pathway was suppressed in macrophages derived from fibrotic kidneys in mice. Knockout of Taz or Tead1 in macrophages inhibited the alternative activation of macrophages and reduced kidney fibrosis. Additionally, by using bone marrow-derived macrophages (BMDMs), we investigated that knockout of Taz or Tead1 in macrophages impeded both cell proliferation and migration. Moreover, deletion of Tead1 reduces p-Smad3 and Smad3 abundance in macrophages. And chromatin immunoprecipitation (ChIP) assays showed that Tead1 could directly bind to the promoter region of Smad3. Collectively, these results indicate that Tead1 knockout in macrophages could reduce TGFß1-induced phosphorylation Smad3 via transcriptional downregulation of Smad3, thus suppressing macrophage alternative activation and IRI-induced kidney fibrosis.

Simultaneous binding of carboxyl and amino groups to liquid metal surface for biosensing.

Eutectic gallium indium (EGaIn) nanoparticles can be modified with aniline derivatives to introduce versatile functional groups toward bioapplications beyond materials science. p-Aminobenzoic acid (PABA) modified EGaIn (EGaIn-PABA) demonstrated high wettability due to the presence of carboxyl groups, but the priority of binding of carboxyl and amino groups on the EGaIn surface remains unclear. To study the binding nature of PABA to EGaIn, the anti-mouse IgG antibody labeled with fluorescein isothiocyanate (FITC) (IgG-FITC) was covalently modified to EGaIn-PABA to verify the presence of terminal carboxyl groups on the EGaIn surface. The binding of gold nanoparticles (AuNPs) to EGaIn-PABA nanoparticles suggested the presence of terminal amino groups on the EGaIn surface. Then, taking advantage of the reductive nature of amino groups, the Almar blue fluorescence experiment was designed to determine the co-existence of carboxyl and amino groups on the EGaIn-PABA surface with an approximate ratio of 3 : 7, suggesting that carboxyl groups had a higher probability of binding with the EGaIn surface than that of amino groups. Then, an aptasensor was fabricated on the EGaIn-PABA surface with AuNPs for electrochemical detection of interleukin-6 with a sensitivity of 1 pg mL-1.

Distinguishable Magnetic Reporter Coordination with Buoyancy-Magnetism Separation for Immobilization-Free Dual-Target Electrochemical Immunosensing.

Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.

Impact of Nitrate on the Removal of Pollutants from Water in Reducing Gas-Based Membrane Biofilm Reactors: A Review.

The membrane biofilm reactor (MBfR) is a novel wastewater treatment technology, garnering attention due to its high gas utilization rate and effective pollutant removal capability. This paper outlines the working mechanism, advantages, and disadvantages of MBfR, and the denitrification pathways, assessing the efficacy of MBfR in removing oxidized pollutants (sulfate (SO4-), perchlorate (ClO4-)), heavy metal ions (chromates (Cr(VI)), selenates (Se(VI))), and organic pollutants (tetracycline (TC), p-chloronitrobenzene (p-CNB)), and delves into the role of related microorganisms. Specifically, through the addition of nitrates (NO3-), this paper analyzes its impact on the removal efficiency of other pollutants and explores the changes in microbial communities. The results of the study show that NO3- inhibits the removal of other pollutants (oxidizing pollutants, heavy metal ions and organic pollutants), etc., in the simultaneous removal of multiple pollutants by MBfR.

Development of a Large Animal Model of Ischemia-free Liver Transplantation in Pigs.

Background: In organ transplantation, ischemia, and reperfusion injury (IRI) is considered as an inevitable event and the major contributor to graft failure. Ischemia-free liver transplantation (IFLT) is a novel transplant procedure that can prevent IRI and provide better transplant outcomes. However, a large animal model of IFLT has not been reported. Therefore, we develop a new, reproducible, and stable model of IFLT in pigs for investigating mechanisms of IFLT in IRI. Methods: Ten pigs were subjected to IFLT or conventional liver transplantation (CLT). Donor livers in IFLT underwent 6-h continuous normothermic machine perfusion (NMP) throughout graft procurement, preservation, and implantation, whereas livers in CLT were subjected to 6-h cold storage before implantation. The early reperfusion injury was compared between the 2 groups. Results: Continuous bile production, low lactate, and liver enzyme levels were observed during NMP in IFLT. All animals survived after liver transplantation. The posttransplant graft function was improved with IFLT when compared with CLT. Minimal histologic changes, fewer apoptotic hepatocytes, less sinusoidal endothelial cell injury, and proinflammatory cytokine (interleukin [IL]-1ß, IL-6, and tumor necrosis factor-α) release after graft revascularization were documented in the IFLT group versus the CLT group. Conclusions: We report that the concept of IFLT is achievable in pigs. This innovation provides a potential strategy to investigate the mechanisms of IRI and provide better transplant outcomes for clinical practice.

Potential role of lipophagy impairment for anticancer effects of glycolysis-suppressed pancreatic ductal adenocarcinoma cells.

Although increased aerobic glycolysis is common in various cancers, pancreatic ductal adenocarcinoma (PDAC) cells can survive a state of glycolysis suppression. We aimed to identify potential therapeutic targets in glycolysis-suppressed PDAC cells. By screening anticancer metabolic compounds, we identified SP-2509, an inhibitor of lysine-specific histone demethylase 1A (LSD1), which dramatically decreased the growth of PDAC PANC-1 cells and showed an anti-tumoral effect in tumor-bearing mice. The growth of glycolysis-suppressed PANC-1 cells was also inhibited by another LSD1 inhibitor, OG-L002. Similarly, the other two PDAC cells (PK-1 and KLM-1) with suppressed glycolysis exhibited anticancer effects against SP-2509. However, the anticancer effects on PDAC cells were unrelated to LSD1. To investigate how PDAC cells survive in a glycolysis-suppressed condition, we conducted proteomic analyses. These results combined with our previous findings suggested that glucose-starvation causes PDAC cells to enhance mitochondrial oxidative phosphorylation. In particular, mitochondrial fatty acid metabolism was identified as a key factor contributing to the survival of PDAC cells under glycolysis suppression. We further demonstrated that SP-2509 and OG-L002 disturbed fatty acid metabolism and induced lipid droplet accumulation through the impairment of lipophagy, but not bulk autophagy. These findings indicate a significant potential association of lipophagy and anticancer effects in glycolysis-suppressed PDAC cells, offering ideas for new therapeutic strategies for PDAC by dual inhibition of glycolysis and fatty acids metabolism.

NDRG1 overcomes resistance to immunotherapy of pancreatic ductal adenocarcinoma through inhibiting ATG9A-dependent degradation of MHC-1.

AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is resistant to immune checkpoint blockade (ICB) therapies. Emerging evidence suggests that NDRG1 may be an important target for the development of new therapies for PDAC. Herein, we investigated the novel roles of NDRG1 and Combretastatin A-4 (CA-4) in the treatment of PDAC ICB resistance. METHODS: Enrichment of MHC class I was detected by RNA sequence and verified by RT-qPCR and immunoblotting in NDRG1-knockdown human pancreatic cancer cell lines. The protein degradation mode was found by stimulation with various inhibitors, and the autophagy degradation pathway was found by immunoprecipitation and immunolocalization. The roles of NDRG1 and MHC-I in immunotherapy were investigated by orthotopic solid tumors, histology, immunohistochemistry, multiplex immunofluorescence staining and flow cytometry. RESULTS: Here, we identified a previously undescribed role of NDRG1 in activating major histocompatibility complex class 1 (MHC-1) expression in pancreatic ductal adenocarcinoma (PDAC) cells through lysosomal-autophagy-dependent degradation. In mouse models of PDAC, either tumor cell overexpression or pharmacologic activation of NDRG1 leads to MHC-1 upregulation in tumor cells, which in turn promotes the infiltration and activity of CD8 + T cells, enhances anti-tumor immunity, and overcomes resistance to ICB therapy. Moreover, combination therapy of CA-4 and ICB overcomes the drug resistance of pancreatic cancer to ICB therapy. In PDAC patients, NDRG1 expression correlates with high MHC-1 expression and better survival. CONCLUSION: Our results reveal NDRG1 in PDAC cancer cells as a tumor suppressor and suggest that pharmaceutically targeting NDRG1 is a promising way to overcome pancreatic cancer resistance to immunotherapy and provides a potential therapeutic strategy for the treatment of pancreatic cancer patients.

Research on farmers' adoption of additional technology combinations: Practice from Chongqing, China.

Tobacco farmers often adopt additional multiple agricultural technologies (AMATs) in addition to implementing the standardized technical system in China. Based on the cross-sectional micro data of 346 households of Chongqing, China, this paper assesses the determinants and impacts of the adoption of AMATs on income by using a multinomial endogenous treatment effects model to correct for selection bias and endogeneity caused by observed and unobserved heterogeneity. The results show that (1) the adoption of combinations of AMATs is determined by the household head's education level, experience in tobacco growing, the shortest distance to nearby town, the amount of technical training, the ratio of land available for mechanical cultivation to tobacco land, the distance to extension station, and the ratio of leased land. (2) The adoption of combinations of AMATs has heterogeneous effects on farmers' income through yield and quality improvement. (3) The comprehensive combination of AMATs is not necessarily the best option for farmers. Due to the interaction between technologies such as complementary, substitute or supplementary effects, the moderate implementation of fertilizers and soil improvement is the most effective combination. The results of this research provide a scientific basis for improving the adoption efficiency of AMATs in China.

Recent advances in natural gums as additives to help the construction and application of edible biopolymer gels: the example of hydrogels and oleogels.

Novel, innovative approaches like edible gels (hydrogels and oleogels) are important food materials with great scientific interest due to their positive impacts on structural and functional foods and other unique properties. Biopolymers (protein, starch and other polysaccharides) can be excellent and cost-effective materials for the formed edible gels. Recently, natural gums, although also as biopolymers, are preferred as additives to further improve the textural and functional properties of edible gels, which have received extensive attention. However, these studies have not been outlined in previous reviews. In this review, we highlighted the advantages of gums as additives to construct edible gels. Moreover, the various roles (including electrostatic or covalent interactions) for natural gums in regulation of food gel properties (solvent-holding and rheological properties) are highlighted. Finally, the use of natural gums as additives to improve the stability and targeted delivery of phytochemicals in food gels and their application in food systems are summarized. The information covered in this article may be useful for the design of functional foods that can better meet personalized needs of people.

Zinc Foliar Application Mitigates Cadmium-Induced Growth Inhibition and Enhances Wheat Growth, Chlorophyll Contents, and Yield.

Cadmium (Cd) is a toxic heavy metal that significantly threatens plants and the environment. Its toxicity in plants can result in various adverse effects, including reduced growth, altered metabolism, and cell damage. Cadmium can also interfere with nutrient uptake, particularly zinc (Zn), leading to Zn deficiency and further exacerbating Cd toxicity. On the other hand, foliar application of zinc might be a useful strategy to mitigate cadmium (Cd) toxicity in plants. Hence, a pot experiment was conducted with three replications. The wheat plants were treated with various concentrations of Zn as a foliar spray (control, 0.1, 0.2, 0.4, and 0.5%) in Cd-spiked soil in pots. The results showed that foliar use of Zn at 0.4 or 0.5% resulted in higher plant height, grain yield, and dry matter yield than the control group. Using Zn as foliar spray enriched shoot and grain Zn content while reducing Cd content in the shoot and grain. The leaf's electrolyte leakage (EL) decreased by 15.4, 29.8, 40.7, and 45.9% in the Zn 0.1%, Zn 0.2%, Zn 0.4%, and Zn 0.5% treatments, respectively, compared to the control treatment. Regarding superoxide dismutase (SOD) activity, Zn 0.5% treatment showed a decrease of 42.9% over control. Specifically, the Zn 0.1% showed a 27.2%, Zn 0.2% showed a 56.8%, Zn 0.4% showed a 91.1%, and Zn 0.5% showed a 133.7% increase in total chlorophyll content than control. Based on the results, it is recommended that 0.4% Zn solution may be used for foliar application for enhancing crop productivity and Zn concentration in plants under high Cd stress. Additionally, continued research on the mechanisms of cadmium uptake, transport, and detoxification in plants may lead to the identification of new targets for intervention.

Co-encapsulation of curcumin and quercetin with zein/HP-ß-CD conjugates to enhance environmental resistance and antioxidant activity.

In this study, composite nanoparticles consisting of zein and hydroxypropyl beta-cyclodextrin were prepared using a combined antisolvent co-precipitation/electrostatic interaction method. The effects of calcium ion concentration on the stability of the composite nanoparticles containing both curcumin and quercetin were investigated. Moreover, the stability and bioactivity of the quercetin and curcumin were characterized before and after encapsulation. Fluorescence spectroscopy, Fourier Transform infrared spectroscopy, and X-ray diffraction analyses indicated that electrostatic interactions, hydrogen bonding, and hydrophobic interactions were the main driving forces for the formation of the composite nanoparticles. The addition of calcium ions promoted crosslinking of the proteins and affected the stability of the protein-cyclodextrin composite particles through electrostatic screening and binding effects. The addition of calcium ions to the composite particles improved the encapsulation efficiency, antioxidant activity, and stability of the curcumin and quercetin. However, there was an optimum calcium ion concentration (2.0 mM) that provided the best encapsulation and protective effects on the nutraceuticals. The calcium crosslinked composite particles were shown to maintain good stability under different pH and simulated gastrointestinal digestion conditions. These results suggest that zein-cyclodextrin composite nanoparticles may be useful plant-based colloidal delivery systems for hydrophobic bio-active agents.

Fascinating Immobilization-Free Electrochemical Immunosensing Strategy Based on the Cooperation of Buoyancy and Magnetism.

Rapid and accurate detection of biomolecules is of vital importance for the diagnosis of disease and for performing timely treatments. The point-of-care analysis of cancer biomarkers in the blood with low cost and easy processing is still challenging. Herein, an advanced and robust strategy, which integrates the buoyant recognition probe with the magnetic reporter probe in one solution, was first proposed for immobilization-free electrochemical immunosensing. The tumor marker of alpha fetoprotein (AFP) can be captured immune-buoyantly, and then a multifunctional magnetic reporter probe in pseudo-homogeneous solution was further captured to fulfill a sandwich-type immunoreaction. The residual magnetic reporter probe can be firmly and efficiently attracted on a magnetic glassy carbon electrode to fulfill the conversion of the target AFP amount into the residual magnetic electrochemical signal indicator. As a result, the electrochemical signal of methylene blue can accurately reflect the original level of target antigen AFP concentration. By integrating buoyancy-driven quasi-homogenous biorecognition with magnetism-mediated amplification and signal output, the proposed immobilization-free electrochemical immunosensing strategy displayed a wide range of linear response (100 fg mL-1 to 10 ng mL-1), low detection limit (14.52 fg mL-1), and good reproducibility, selectivity, and stability. The designed strategy manifests remarkable advantages including assay simplicity, rapidness, and high sensitivity owing to the in-solution instead of on-electrode biorecognition that could accelerate and improve the biorecognition efficiency. To the best of our knowledge, this is the first cooperation of buoyancy-driven biorecognition with magnetism-mediated signal output in bioanalysis, which would be attractive for rapid clinic biomedical application. Thus, this work provides a fresh perspective for convenient and favorable immobilization-free electrochemical biosensing of universal biomolecules.

Metabolomics Differences of the Donor Livers Between In Situ and Ex Situ Conditions During Ischemia-free Liver Transplantation.

BACKGROUND: Ischemia-free liver transplantation (IFLT) has been innovated to avoid graft ischemia during organ procurement, preservation, and implantation. However, the metabolism activity of the donor livers between in the in situ and ex situ normothermic machine perfusion (NMP) conditions, and between standard criteria donor and extend criteria donor remains unknown. METHODS: During IFLT, plasma samples were collected both at the portal vein and hepatic vein of the donor livers in situ during procurement and ex situ during NMP. An ultra-high performance liquid chromatography-mass spectrometry was conducted to investigate the common and distinct intraliver metabolite exchange. RESULTS: Profound cysteine and methionine metabolism, and aminoacyl-tRNA biosynthesis were found in both in situ and ex situ conditions. However, obvious D-arginine and D-ornithine metabolism, arginine and proline metabolism were only found in the in situ condition. The suppressed activities of the urea cycle pathway during ex situ condition were confirmed in an RNA expression level. In addition, compared with extend criteria donor group, standard criteria donor group had more active intraliver metabolite exchange in metabonomics level. Furthermore, we found that the relative concentration of p-cresol, allocystathionine, L-prolyl-L-proline in the ex situ group was strongly correlated with peak alanine aminotransferase and aspartate aminotransferase at postoperative days 1-7. CONCLUSIONS: In the current study, we show the common and distinct metabolism activities during IFLT. These findings might provide insights on how to modify the design of NMP device, improve the perfusate components, and redefine the criteria of graft viability.

Physicochemical stability, antioxidant activity, and antimicrobial activity of quercetin-loaded zein nanoparticles coated with dextrin-modified anionic polysaccharides.

Core-shell biopolymer nanoparticles are assembled from a hydrophobic protein (zein) core and a hydrophilic polysaccharide (carboxymethyl dextrin) shell. The nanoparticles were shown to have good stability and the ability to protect quercetin from chemical degradation under long-term storage, pasteurization, and UV irradiation. Spectroscopy analysis shows that electrostatic, hydrogen bonding, and hydrophobic interactions are the main driving forces for the formation of composite nanoparticles. Quercetin coated with nanoparticles significantly enhanced its antioxidant and antibacterial activities and showed good stability and slow release in vitro during simulated gastrointestinal digestion. Furthermore, the encapsulation efficiency of carboxymethyl dextrin-coated zein nanoparticles (81.2%) for quercetin was significantly improved compared with that of zein nanoparticles alone (58.4%). These results indicate that carboxymethyl dextrin-coated zein nanoparticles can significantly improve the bioavailability of hydrophobic nutrient molecules such as quercetin and provide a valuable reference for their application in the field of biological delivery of energy drinks and food.

The Liver Tumor Segmentation Benchmark (LiTS).

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in http://medicaldecathlon.com/. In addition, both data and online evaluation are accessible via https://competitions.codalab.org/competitions/17094.

PINK1-dependent and Parkin-independent mitophagy is involved in reprogramming of glycometabolism in pancreatic cancer cells.

Cancer cells rely on glycolysis to generate ATP for survival. However, inhibiting glycolysis is insufficient for the eradication of cancer cells because glycolysis-suppressed cells undergo metabolic reprogramming toward mitochondrial oxidative phosphorylation. We previously described that upon glycolytic suppression in pancreatic cancer cells, intracellular glycometabolism is shifted toward mitochondrial oxidative phosphorylation in an autophagy-dependent manner for cellular survival. Here, we hypothesized that mitophagy, which selectively degrades mitochondria via autophagy, is involved in mitochondrial activation under metabolic reprogramming. We revealed that glycolytic suppression notably increased mitochondrial membrane potential and mitophagy in a pancreatic cancer cell model (PANC-1). PTEN-induced kinase 1 (PINK1), a ubiquitin kinase that regulates mitophagy in healthy cells, regulated mitochondrial activation through mitophagy by glycolytic suppression. However, Parkin, a ubiquitin ligase regulated by PINK1 in healthy cells to induce mitophagy, was not involved in the PINK1-dependent mitophagy of the cancer glycometabolism. These results imply that cancer cells and healthy cells have different regulatory pieces of machinery for mitophagy, and inhibition of cancer-specific mechanisms may be a potential strategy for cancer therapy targeting metabolic reprogramming.

Activation of adenosine A3 receptor attenuates progression of osteoarthritis through inhibiting the NLRP3/caspase-1/GSDMD induced signalling.

The specific adenosine A3 receptor (A3AR) agonist (CF101) has potential for inflammation and pain in various disease, such as arthritis, cancer and neuropathic pain, while the role of A3AR in post-traumatic OA and the underlying mechanism is largely unknown. CF101 was orally administrated in OA rats induced by anterior cruciate ligament transection (ACLT) surgery, and the rat primary chondrocytes were stimulated by hydrogen peroxide (H2 O2 , 300 µM). Histologic grading system was performed for detecting cartilage degeneration and immunohistochemistry for determining pyroptosis. The moleculars associated with cartilage homeostasis and inflammatory cytokines were analysed; moreover, the activation of NLRP3 inflammasome was determined. CF101 treatment significantly attenuated OA cartilage damage, OA-related pain and cartilage pyroptosis. Chondrocytes stimulated by H2 O2 evoked ROS release, thereby promoting the activation of NLRP3 inflammasome and facilitating the cleavage of GSDMD, which ultimately resulted in the mass release of pro-inflammatory cytokines including IL-1ß and IL-18, and production of matrix hydrolase. The pre-treatment with CF101 powerfully inhibited the above process both in vivo and in vitro. Our findings demonstrated that activation of A3AR attenuates OA progression and relieves pain perception through suppression of cartilage degradation and inhibition of ROS/NLRP3/GSDMD signalling, indicating pyroptosis is a potential candidate for OA treatment.

Polyphenols as Plant-Based Nutraceuticals: Health Effects, Encapsulation, Nano-Delivery, and Application.

Plant polyphenols have attracted considerable attention because of their key roles in preventing many diseases, including high blood sugar, high cholesterol, and cancer. A variety of functional foods have been designed and developed with plant polyphenols as the main active ingredients. Polyphenols mainly come from vegetables and fruits and can generally be divided according to their structure into flavonoids, astragalus, phenolic acids, and lignans. Polyphenols are a group of plant-derived functional food ingredients with different molecular structures and various biological activities including antioxidant, anti-inflammatory, and anticancer properties. However, many polyphenolic compounds have low oral bioavailability, which limits the application of polyphenols in nutraceuticals. Fortunately, green bio-based nanocarriers are well suited for encapsulating, protecting, and delivering polyphenols, thereby improving their bioavailability. In this paper, the health benefits of plant polyphenols in the prevention of various diseases are summarized, with a review of the research progress into bio-based nanocarriers for the improvement of the oral bioavailability of polyphenols. Polyphenols have great potential for application as key formulations in health and nutrition products. In the future, the development of food-grade delivery carriers for the encapsulation and delivery of polyphenolic compounds could well solve the limitations of poor water solubility and low bioavailability of polyphenols for practical applications.