Feasibility of Tenebrio molitor larvae protein to partially replace lean meat in the processing of hybrid frankfurters: Perspectives on quality profiles and in vitro digestibility.

The aim of this study was to investigate the effect of replacing different amounts (5 %, 10 %, 15 %, 20 % and 25 %) of lean meat with Tenebrio molitor larvae protein (TMLP) on the quality profiles of hybrid frankfurters. The results showed that there were no obvious differences in moisture, protein or fat content of all the hybrid frankfurters (P > 0.05), only a higher substitution rate (from 10 % to 25 %) resulted in a higher ash content than the control group (P < 0.05). With the increasing replacement rate (5 %, 10 % and 15 %), the cooking loss of the hybrid frankfurters showed the similar effects as the control group (P > 0.05), whereas the higher replacement rates of 20 % and 25 % obviously decreased the emulsion stability of the hybrid frankfurters. Moreover, with lower substitution rate (5 %, 10 % and 15 %) there were no significant differences in cooking loss between the hybrid frankfurters and the control group (P > 0.05), whereas the higher substitution rates (20 % and 25 %) obviously increased the cooking loss of the hybrid frankfurters (P < 0.05). Meanwhile, as the level of substitution increased, the hybrid frankfurters had higher digestibility, poorer texture than the standard frankfurters, as well as the rheological behaviour of hybrid meat batters (P < 0.05). The results showed that a moderate level (15 %) of TMLP was used to replace lean pork could be potentially and successfully be used to produce hybrid frankfurters.

Controllable synthesis of a Na-enriched Na4V2(PO4)3 cathode for high-energy sodium-ion batteries: a redox-potential-matched chemical sodiation approach.

Exploring a sodium-enriched cathode (i.e. Na4V2(PO4)3, which differs from its traditional stoichiometric counterpart Na3V2(PO4)3 that can provide extra endogenous sodium reserves to mitigate the irreversible capacity loss of the anode material (i.e. hard carbon), is an intriguing presodiation method for the development of high energy sodium-ion batteries. To meet this challenge, herein, we first propose a redox-potential-matched chemical sodiation approach, utilizing phenazine-sodium (PNZ-Na) as the optimal reagent to sodiate the Na3V2(PO4)3 precursor into Na-enriched Na4V2(PO4)3. The spontaneous sodiation reaction enables a fast reduction of one-half V ions from V3+ to V2+, followed by the insertion of one Na+ ion into the NASICON framework, which only takes 90 s to obtain the phase-pure Na4V2(PO4)3 product. When paired with a hard carbon anode, the resulting Na4VP‖HC full cell exhibits a high energy density of 251 W h kg-1, which is 58% higher than that of 159 W h kg-1 for the Na3VP‖HC control cell. Our chemical sodiation methodology provides an innovative approach for designing sodium-rich cathode materials and could serve as an impetus to the development of advanced sodium-ion batteries.

Ultrasound-assisted alkaline extraction of protein from Tenebrio molitor larvae: Extraction kinetics, physiochemical, and functional traits.

Currently, as a promising alternative protein source, the interest of edible insect protein has been continuously increased. However, the extraction processing had distinct effects on the physicochemical properties and functionalities of this novel and sustainable protein. In this study, Tenebrio molitor larvae protein (TMLP) was extracted via ultrasound (US)-assisted alkaline extraction. The changes of extraction kinetics, physicochemical characteristics, and functional properties of TMLP as a function of US time (10, 20, 30, 40, 50 min) were investigated. The results showed that 30 min US treatment rendered the maximum protein yield (60.04 %) (P < 0.05). Meanwhile, Peleg's model was considered a suitable model to represent the extraction kinetics of TMLP, with a correlation coefficient of 0.9942. Moreover, the protein secondary structure, particle size, and amino acid profiles of TMLP were changed under the US-assisted alkaline extraction process. Additionally, a significant improvement of the functional properties of TMLP extracted with this method was observed compared to traditional alkaline extraction. In conclusion, the present work suggests that US-assisted alkaline extraction could be considered as a potential method to improve the protein yield, quality profiles, and functional properties of TMLP.

Mechanisms underlying the effects of ultrasound-assisted alkaline extraction on the structural properties and in vitro digestibility of Tenebrio molitor larvae protein.

Edible insects have been considered as a sustainable and novel protein source to replace animal-derived proteins. The present study aimed to extract Tenebrio molitor larvae proteins (TMP) using ultrasound-assisted alkaline extraction (UAE). Effects of different UAE times (10, 20, 30, 40, and 50 min) on the structural properties and in vitro digestibility of TMP were comparatively investigated with the traditional alkaline extraction method. The results revealed that ultrasonication could effectively alter the secondary/tertiary structures and thermal stability of TMP during UAE. The molecular unfolding and subsequent aggregation of TMP during UAE were mainly attributed to the formation of disulfide bonds and hydrophobic interactions. Moreover, TMP extracted by UAE had higher in vitro digestibility and digestion kinetics than those extracted without ultrasound, and the intermediate UAE time (30 min) was the optimal ultrasound parameter. However, longer UAE times (40 and 50 min) lowered the digestibility of TMP due to severe protein aggregation. The present work provides a potential strategy for the extraction of TMP with higher nutritional values.

Application of seaweed dietary fiber as a potential alternative to phosphates in frankfurters with healthier profiles.

This study was designed to investigate the utilization of seaweed dietary fiber (SDF) as a potential alternative to phosphates on the quality profiles of phosphate-free frankfurters. The results showed that the incorporation of SDF obviously promote the textural parameters of phosphate-free frankfurters, which was effectively verified by scanning electron microscopy. Meanwhile, SDF effectively retarded lipid oxidation of phosphate-free frankfurters during storage (P < 0.05). Moreover, 1.00% SDF was proven to show the best optimal phosphates replacing effect, as well as overcome the quality defects of phosphate-free frankfurters to the maximum extent. In addition, hydrogen bonding and hydrophobic interactions were the primary molecular force in SDF-added phosphate-free frankfurters. Therefore, our results implied that SDF can be considered as a feasible alternative for the processing of phosphate-free frankfurters with improved quality profile and superior health benefits which consistent with the demand of healthier meat products.

Nigakinone alleviates DSS-induced experimental colitis via regulating bile acid profile and FXR/NLRP3 signaling pathways.

The correlation of bile acid (BA) metabolism disorder with the pathogenesis of ulcerative colitis (UC) is realized nowadays. Farnesoid X receptor (FXR), a controller for BA homeostasis and inflammation, is a promising target for UC therapy. Nigakinone has potential therapeutic effects on colitis. Herein, we investigated the anti-UC effects and mechanism of nigakinone in colitic animals induced by dextran sulfate sodium (DSS). The related targets involved in the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) signaling pathway were measured. BA-targeted metabolomics was employed to reveal the regulatory effects of nigakinone on BA profile in colitis, while expressions of FXR and its mediated targets referring to BA enterohepatic circulation were determined. The critical role of FXR in the treatment of nigakinone for colitis was studied via molecule-docking, dual-luciferase reporter® (DLR™) assays, FXR silencing cells, and FXR knockout mice. Results showed nigakinone attenuated DSS-induced colitis symptoms, including excessive inflammatory response by NLRP3 activation, and injury of the intestinal mucosal barrier. Nigakinone regulated BA disorders by controlling cholesterol hydroxylase and transporters mediated by FXR, then decreased BA accumulation in colon. Molecular-docking and DLR™ assays indicated FXR might be a target of nigakinone. In vitro, nigakinone restrained BA-induced inflammation and cell damage via FXR activation and inhibition of inflammatory cytokines. However, ameliorating effects of nigakinone on colitis were suppressed by FXR knockout or silencing in vivo or in vitro. Taken together, nigakinone ameliorated experimental colitis via regulating BA profile and FXR/NLRP3 signaling pathway.

Paclitaxel-loaded ginsenoside Rg3 liposomes for drug-resistant cancer therapy by dual targeting of the tumor microenvironment and cancer cells.

INTRODUCTION: Inherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various targeted drug-delivery systems, including nanoparticles and liposomes, are effective for MDR cancer treatment, their efficacy is restricted by immunosuppressive tumor microenvironment (TME). METHODS: Ginsenosides Rg3 was used to formulate unique Rg3-based liposomes loaded with PTX to establish Rg3-PTX-LPs, which were prepared by the thin-film hydration method. The stability of the Rg3-PTX-LPs was evaluated by particle size analysis through dynamic light scattering. The active targeting effect of Rg3-based liposomes was examined in an MCF-7/T xenograft model by an in a vivo imaging system. To evaluate the antitumor activity and mechanism of Rg3-PTX-LP, MTT, apoptosis assays, TAM regulation, and TME remodeling were performed in MCF-7/T cells in vitro and in vivo. RESULTS: Rg3-PTX-LPs could specifically distribute to MCF7/T cancer cells and TME simultaneously, mainly through the recognition of GLUT-1. The drug resistance reversing capability and in vivo antitumor effect of Rg3-PTX-LPs were significantly improved compared with conventional cholesterol liposomes. The TME remodeling mechanisms of Rg3-PTX-LPs included inhibiting IL-6/STAT3/p-STAT3 pathway activation to repolarize protumor M2 macrophages to antitumor M1 phenotype, suppressing myeloid-derived suppressor cells (MDSCs), decreasing tumor-associated fibroblasts (TAFs) and collagen fibers in TME, and promoting apoptosis of tumor cells. Hence, through the dual effects of targeting tumor cells and TME remodeling, Rg3-PTX-LPs achieved a high tumor inhibition rate of 90.3%. CONCLUSION: Our multifunctional Rg3-based liposome developed in the present study offered a promising strategy for rescuing the drug resistance tumor treatment.

Additive Effects of L-Arginine with Potassium Carbonate on the Quality Profile Promotion of Phosphate-Free Frankfurters.

The present study investigated the additive effects of L-Arginine (L-Arg) with potassium carbonate (PC) on the quality characteristics of phosphate-free frankfurters. The results showed that L-Arg combined with PC could act as a viable phosphate replacer by decreasing cooking loss and improving the textural properties of phosphate-free frankfurters (p < 0.05), mainly because of its pH-raising ability. Moreover, L-Arg could assist PC in effectively retarding lipid oxidation in phosphate-free frankfurters during storage (p < 0.05). Furthermore, 0.1% L-Arg combined with 0.15% PC was found to exhibit the best optimal phosphate-replacing effect. This combination could also overcome quality defects and promote the sensory attributes of phosphate-free frankfurters to the maximum extent. Therefore, our results suggest that L-Arg combined with PC can be considered a feasible alternative for the processing of phosphate-free frankfurters with an improved quality profile and superior health benefits.

Comparative study of two types of pre-extraction treatment (drying or non-drying) on physicochemical, structural and functional properties of extracted insect proteins from Tenebrio molitor larvae.

Microwave drying (MD) or freeze drying (FD) was commonly used as a drying treatment prior to the extraction of edible insect proteins. However, some quality defects (e.g., lipid oxidation or protein denaturation) were probably occurred via the drying step. To this end, the effect of drying or non-drying treatments (ND) after slaughtering by liquid nitrogen freezing on the physicochemical characteristics, structural and functional properties of Tenebrio molitor larvae protein (TMP) was investigated. The results indicate that TMP extracted from the ND group showed higher essential/total amino acid content, total/free sulfhydryl content, surface hydrophobicity, solubility, water/oil holding capacities, and emulsifying/foaming properties than those extracted from the MD or FD groups (P < 0.05). Moreover, the ND group had minimal impact on the structural changes of TMP which was associated with protein denaturation. Therefore, it can be concluded that a non-drying strategy prior to TMP extraction can improve functional properties and retard protein denaturation, while also conserving energy.

Erythropoietin mediates re-programming of endotoxin-tolerant macrophages through PI3K/AKT signaling and protects mice against secondary infection.

Initial lipopolysaccharide (LPS) exposure leads to a hypo-responsive state by macrophages to a secondary stimulation of LPS, known as endotoxin tolerance. However, recent findings show that functions of endotoxin-tolerant macrophages are not completely suppressed, whereas they undergo a functional re-programming process with upregulation of a panel of molecules leading to enhanced protective functions including antimicrobial and tissue-remodeling activities. However, the underlying molecular mechanisms are still elusive. Erythropoietin (EPO), a glycoprotein regulated by hypoxia-inducible factor 1α (HIF-1α), exerts anti-inflammatory and tissue-protective activities. Nevertheless, the potential effects of EPO on functional re-programming of endotoxin-tolerant macrophages have not been investigated yet. Here, we found that initial LPS exposure led to upregulation of HIF-1α/EPO in macrophages and that EPO enhanced tolerance in tolerized macrophages and mice as demonstrated by suppressed proinflammatory genes such as Il1b, Il6, and Tnfa after secondary LPS stimulation. Moreover, we showed that EPO improved host protective genes in endotoxin-tolerant macrophages and mice, such as the anti-bacterial genes coding for cathelicidin-related antimicrobial peptide (Cnlp) and macrophage receptor with collagenous structure (Marco), and the tissue-repairing gene vascular endothelial growth factor C (Vegfc). Therefore, our findings indicate that EPO mediates the functional re-programming of endotoxin-tolerant macrophages. Mechanistically, we found that PI3K/AKT signaling contributed to EPO-mediated re-programming through upregulation of Irak3 and Wdr5 expression. Specifically, IL-1 receptor-associated kinase 3 (IRAK3) was responsible for inhibiting proinflammatory genes Il1b, Il6, and Tnfa in tolerized macrophages after LPS rechallenge, whereas WDR5 contributed to the upregulation of host beneficial genes including Cnlp, Marco, and Vegfc. In a septic model of mice, EPO pretreatment significantly promoted endotoxin-tolerant re-programming, alleviated lung injury, enhanced bacterial clearance, and decreased mortality in LPS-tolerized mice after secondary infection of Escherichia coli. Collectively, our results reveal a novel role for EPO in mediating functional re-programming of endotoxin-tolerant macrophages; thus, targeting EPO appears to be a new therapeutic option in sepsis and other inflammatory disorders.

Inhibition of NLRP3-mediated crosstalk between hepatocytes and liver macrophages by geniposidic acid alleviates cholestatic liver inflammatory injury.

The excessive accumulation of bile acids (BA) in hepatocytes can trigger inflammatory response and recruit macrophages, thereby accelerating cholestatic liver injury. The crosstalk between hepatocytes and macrophages has been recently implicated in the pathogenesis of cholestasis; however, the underlying mechanisms remain unclear. Here, we demonstrated that BA initiate NLRP3 inflammasome activation in hepatocytes to release proinflammatory cytokines and promote the communication between hepatocytes and macrophages, thus enhancing liver inflammation in an NLRP3-dependent manner. NLRP3-inhibition by geniposidic acid (GPA), a novel NLRP3-specific covalent inhibitor that directly interacts with NLRP3, in hepatocytes and macrophages abated BA-induced inflammation. Moreover, NLRP3-deletion or its inhibition mitigated ANIT-induced cholestatic inflammation, whereas disrupting the crosstalk between hepatic macrophages and hepatocytes attenuated the hepatoprotective effect of GPA against ANIT-induced cholestatic inflammation. Therefore, blocking this crosstalk by suppressing NLRP3 inflammasome activation may represent a novel therapeutic strategy for cholestasis.

Ultralow-Loading and High-Performing Ionic Liquid-Immobilizing Rhodium Single-Atom Catalysts for Hydroformylation.

We have developed a Keggin polyoxometalate (POM)-based ionic-liquid (IL)-immobilizing rhodium single-atom Rh catalyst (MTOA)5 [SiW11 O39 Rh] (MOTA=methyltrioctylammonium cation) that can afford exceptionally high catalytic activity for the hydroformylation of alkenes to produce aldehydes at an ultralow loading of Rh (ca. 3 ppm). For styrene hydroformylation, both the conversion and the yield of the aldehyde can reach almost 99 %, and a TOF as high as 9000 h-1 was obtained without using any phosphine ligand in the reaction process. Further characterization by FTIR, ICP and ESI-MS analysis revealed that the single Rh atom was incorporated in the lacunary POM anions. In particular, the bulky IL cation can play an additional role in stabilizing Rh species and thus prevent aggregation and leaching of Rh species. The IL catalyst was miscible with n-hexane at temperatures; this contributed to exceptionally high activity for hydroformylation even at ultra-low loading of IL catalyst.

Corrigendum: Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/ß-Catenin/ABCG2 Axis.

[This corrects the article DOI: 10.3389/fphar.2021.659297.].

Pre-dried mealworm larvae flour could partially replace lean meat in frankfurters: Effect of pre-drying methods and replacement ratios.

This study aimed to investigate the effect of replacing different amounts (5%, 10%, and 15%) of lean meat with yellow mealworm larvae (Tenebrio molitor L.) flour (YMLF) obtained via two different pre-drying methods on the quality profiles of hybrid frankfurters. With the increasing replacement ratio, the cooking loss of the freeze-dried YMLF (FD-YMLF) groups gradually increased, whereas those of the microwave drying YMLF (MD-YMLF) groups were always better than those of the control group (P < 0.05). Moreover, the MD-YMLF group showed superior textural properties than FD-YMLF group under the same replacement ratio (P < 0.05), especially for MD-YMLF-10% group. Additionly, with the increasing replacement ratio, the hybrid frankfurters had lower sensorial scores than standard frankfurters (P < 0.05), whereas the MD-YMLF group was always better than the FD-YMLF group for the same replacement ratio (P < 0.05). Our results indicated that MD-YMLF could be used as a potential lean meat replacement to process emulsified meat products.

Optimal sensor placement method for wastewater treatment plants based on discrete multi-objective state transition algorithm.

Parameters monitoring is essential to maintain the stability and efficiency of the wastewater treatment process, which has spurred ubiquitous installation of sensors in wastewater treatment plants (WWTPs). As the rich process data of WWTPs is not effectively transformed into actionable knowledge for system optimization due to improper sensor installation, the sensor placement scheme needs to be optimized. In this paper, a weighted sensor placement optimization model based on sensor cost, information richness and reliability is established to transform the sensor optimization problem to a nonlinear mathematical programming problem. Then a discrete multi-objective state transition algorithm is proposed to find the Pareto optimal solutions. Finally, an evaluation strategy is designed to select the most suitable solution for industrial application. The results of simulation experiments on three different WWTPs demonstrate the validity and superiority of the proposed method, increasing the degree of variable observability and measurement redundancy while keeping the sensor cost at a low level.

Optimal setting strategy of electrocoagulation process in heavy metal wastewater treatment plant.

With the increasingly stringent environmental protection policies of various countries, the contradiction between the treatment cost and the purification degree of environmental pollutants has become increasingly significant, which has become a major factor restricting the efficient operation of wastewater treatment plants. Hence, keeping the ion concentration at the outlet as low as possible while reducing the cost are the main objectives of treating heavy metal wastewater by electrocoagulation (EC) process. However, due to the complicated mechanism and uncertain production conditions, it is difficult to achieve those goals by manually setting the current through operators' experience. In this paper, we develop a dynamic multi-objective optimization strategy for EC process to balance these two conflicting production targets. First, we define the removal efficiency (RE) to measure the effectiveness of the EC process. Due to the anodic passivation and cathodic polarization in the EC process, the current reversing period (CRP) is proposed and optimized to ensure the stable performance of the electrodes. Then the current setting problem is formulated as a constrained multi-objective optimization problem with competing objectives of RE and cost. An interval-adjustable control parameterization (CP) approach is developed to reduce the complexity of this optimization problem. To compute this optimization problem, a heuristic method named multi-objective state transition algorithm (MOSTA) with evaluation value is investigated. The effectiveness of our model and optimization strategy is demonstrated by a successful implementation in an EC process of a wastewater treatment plant in Chenzhou, China.

Ras inhibitor farnesylthiosalicylic acid conjugated with IR783 dye exhibits improved tumor-targeting and altered anti-breast cancer mechanisms in mice.

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy.