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Pea protein has attracted great attention due to its capability to meet the growing requirements from consumers for desired nutrition and texture from plant protein. Hence, the current study aimed to investigate the effects of different ultrasonic treatment parameters (power and duration) on the gelling characteristics of commercial pea protein isolates (PPIc). The findings demonstrated that by manipulating the ultrasonic power and treatment duration, great enhancement of the solubility, adhesiveness and formation strength of PPIc gel can be realized. The reduction in particle size was positively correlated with higher power and longer treatment durations. Interestingly, no direct correlation between average particle size, solubility, turbidity, and ζ-potential was observed. Additionally, the ultrasound-modified PPIc in this study exhibited comparable characteristics to laboratory-prepared pea protein isolates, in terms of solubility, water-holding capacity, and gel strength. Overall, manipulating ultrasonic parameters presents a feasible method to customize the texture of pea-protein-based substitute. [Display omitted] • Prolonged ultrasound enhances the viscosity of PPIc. • Ultrasound can moderately adjust the gel hardness of PPIc (from 10.8 g to 41.2 g) • PPIc modified by ultrasound displayed similar performance in rheology properties as native PPI. • The effect of ultrasonic on PPIc is related to the total energy applied. • Ultrasound was used to improve the processing characteristics of commercial proteins. [ABSTRACT FROM AUTHOR]

The incorporation of nutrients with immunomodulatory properties into the daily diet has emerged as a pressing health requirement. The aim of this study was to screen apple polyphenols with immunomodulatory activitiy using molecular docking and to investigate the modulatory effects of apple polyphenol-isochlorogenic acid A on the activation of macrophage immune responses and the inhibition of inflammation through the immunoreceptors TLR2 and TLR4. The results showed that isochlorogenic acid A of apple polyphenols had high docking scores with TLR2 and TLR4. The isochlorogenic acid A exhibited favorable ADMET properties and water solubility. Cellular assays results showed that isochlorogenic acid A enhanced the viability of RAW264.7 cells and promoted the expression of NO, TNF-α, IL-1β, TLR2, and TLR4 in cells, and inhibited the expression of NO, TNF-α, IL-6, TLR2, and TLR4 in inflammatory cells. The isochlorogenic acid A bound to residues Phe325, Phe349, Leu350 and Pro352 of TLR2 by hydrogen bonding and hydrophobic interactions, and to residues Val82, Arg90, Ser127, Cys133 and Ser441 of TLR4-MD-2 via π-alkyl and hydrogen bonds. In summary, the immunoreceptors TLR2 and TLR4 play a crucial role as recognition receptors for isochlorogenic acid A of apple polyphenols in the regulation of cellular immune response and inflammation. [Display omitted] • Isochlorogenic acid A from apple had immunomodulatory activity. • Isochlorogenic acid A had high binding affinity to TLR2 and TLR4. • Isochlorogenic acid A bound to TLR2/4 via hydrogen bonding and hydrophobic interactions. • Isochlorogenic acid A could bidirectionally regulate the expression of NO and cytokines. [ABSTRACT FROM AUTHOR]

Peiminine (PMI) is an active alkaloid sourced from Fritillaria thunbergii , which has been shown to suppress the development of a variety of tumors. Whereas, the roles and precise mechanism of PMI in breast cancer (BC) development remain not been clarified. The cytotoxic effect of PMI on MCF-10A and BC cell lines (MCF-7 and BT-549) were assessed by MTT and LDH release assay. Cell proliferation was evaluated by EdU staining. Levels of Malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH) activity and iron assay were measured by Enzyme linked immunosorbent assay (ELISA) kits, respectively. Transmission Electron Microscope was performed to observe mitochondrial morphological structure. Immunofluorescence, immunohistochemistry, and western blot were conducted to examine protein levels, respectively. Xenograft model was used to confirm cellular findings. PMI treatment reduced the viability and enhanced LDH level of MCF-7 and BT-549 cells in a time- and concentration-dependent manner, and further suppressed cell proliferation in vitro and tumor growth in vivo. Subsequently, PMI administration resulted in significant increases of ROS, MDA and iron levels, reduction of GSH activity as well as mitochondrial shrinkage and GPX4 reduction, while all these phenomena could be rescued by ferrostatin-1. Mechanistically, PMI treatment led to promoted Nrf2 expression and its nuclear translocation, as well as it's downstream protein HO-1 and NQO1 expressions. Notably, ML-385, a Nrf2 specific inhibitor, greatly reversed the anti-tumor effects and pro-ferroptosis role of PMI in BC cells. Taking these finding together, PMI could stimulate ferroptosis to inhibit BC tumor growth by activating Nrf2-HO-1 signaling pathway. • Peiminine suppressed the proliferation of breast cancer cells in a time-/concentration dependent manner. • Peiminine led to mitochondrial shrinkage and ferroptosis in breast cancer. • Peiminine triggered ferroptosis to restrain breast cancer growth by suppressing Nrf2 signaling. [ABSTRACT FROM AUTHOR]

To investigate the relationship between maternal serum fatty acid levels and gestational diabetes mellitus (GDM) subtypes across pregnancy. A total of 680 singleton mothers enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included. Clinical information and serum samples were collected at gestational weeks (GWs) 11–14, 22–28, and 32–34. 75 g Oral Glucose Tolerance Test (OGTT) was conducted at GW 24–28 and GDM subtypes divided into three groups using International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines criteria: elevated fasting plasma glucose (FPG group; n = 59); 1-h and/or 2-h post-load glucose (1h/2h-PG group; n = 94); combined group (FPG&1h/2h-PG group; n = 42). Non-GDM pregnancies were included (n = 485) as controls. Twenty fatty acids were quantified in serum using gas chromatography-mass spectrometry (GC–MS) analysis. Overall, most serum fatty acid concentrations increased rapidly from the first to second trimester, followed by a plateauing or reduction in the third trimester (p < 0.001). In cross sectional analysis, fatty acid concentrations were significantly higher in the FPG group at GW 11–14 and decreased in the 1h/2h-PG group at GW 32–34, relative to controls. Moreover, higher α-linolenic acid (ALA; the second tertile: adjusted odds ratio [aOR] = 2.53, 95% CI: 1.17 to 5.47; the third tertile: aOR = 2.60, 95% CI: 1.20 to 5.65) and docosahexaenoic acid (DHA; the second tertile: aOR = 2.34, 95% CI: 1.10 to 4.97; the third tertile: aOR = 2.16, 95% CI: 1.00 to 4.63) were significantly associated with a higher risk of GDM in women with elevated fasting plasma glucose at GW 11–14 (first tertile as reference). Our findings highlight the importance of considering GDM subtypes for the individualised management of GDM in pregnancy. ALA and DHA in early pregnancy are associated with a higher risk of FPG-GDM subtype. This has widespread implications when recommending n-3 PUFAs supplementation for women with GDM. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H 2 S) is an appealing signaling molecule that plays fundamental roles in health and disease. However, H 2 S-mediated selective chemical transformations for the construction of imaging probes are limited, retarding the interrogation of H 2 S-related biological processes. Here, we present an alternative approach for engineering a new generation of efficient probes with a nonchemoselective moiety as a building block. To demonstrate our design concept, we developed a sulfoxide-functionalized BODIPY that exhibited a substantial redshift in its absorption and emission spectra upon reduction with H 2 S. However, such a probe also showed reactivity toward various competing biothiols under aqueous buffer conditions. To achieve high chemoselectivity, we used core-shell silica nanoparticles as an encapsulation matrix to confine the designed molecule probe within their interiors. The inherent molecular-size sieving character of the porous silica shell was capable of impeding competing biothiols from accessing the molecule probe within the core while allowing the specific reaction with the small target H 2 S. Thus, this strategy avoided disturbance from coexisting biothiols and achieved highly chemoselective detection in ratiometric and near-infrared (NIR) turn-on fluorescence modes. In light of these promising features, together with fast responsiveness and favorable cellular uptake, such a silica nanocomposite was successfully used to detect the endogenous production of H 2 S in estrogen-induced cardiomyocytes and living mouse model. To our knowledge, the approach reported here is the first to exploit the usefulness of common thiol-sensitive moieties for building chemoselective probes. [ABSTRACT FROM AUTHOR]

Providing texture-modified food for dysphagia patients has been one of the most effective treatment methods. The current study aimed to evaluate a specially designed commercial pea protein isolate (PPIc) -based texture-modified food by ultrasonic treatment (US, 390 W; 20 min) at different NaCl concentrations by adjusting its texture and structure. The results showed that US can improve the texture properties of PPIc within a certain range of NaCl concentration (0.03–0.6 M). The prepared PPIc samples exhibited good mastication and swallowing characteristics with proper viscosity (33.31–704.2 mPa·s), softness (gel strength <30 g), wetness (good solubility and water holding capacity), etc. While with ultrasonic condition at the low NaCl concentration (0.1 M), the PPIc could achieve an overall superior textural attribute than those with other salt concentrations. Further research showed that US-NaCl combination could facilitate PPIc gel to maintain a more proper dysphagia texture, not only by reducing the number of pores and unfolding structures during processing, but also by enhancing the surface area of protein particles and cross-linking interaction of proteins through more exposure of sulfhydryl groups. It was also found that the β-turns of untreated-PPIc transformed to β-sheets at high salt concentration, whereas inverted transformation was observed at low NaCl concentration (0.03 M). We further unveiled US significantly enhanced the solubility, water holding capacity, and gelling ability of the PPIc. Overall, US-NaCl would be a promising method for the preparation of modified textural PPIc, which provides a new approach to formulate low-salt, high-nutrition, and customizable food for special populations such as the elderly and dysphagia. [Display omitted] • US-NaCl increased PPIc-based dysphagia food viscosity variably. • US-PPIc at 0.1 M NaCl showed superior texture compared to other salt concentrations. • US improved PPIc's solubility, water holding capacity, and gelling ability. • US significantly increased PPIc's surface hydrophobicity and free SH content. • US-NaCl combination effectively formulates texture-modified food. [ABSTRACT FROM AUTHOR]

Cyanidins are considered the most widespread anthocyanin in nature, and the cyanidin-3-O-arabinoside from apple with anti-tumor activity has been screened in our previous study. However, the anti-tumor mechanism of cyanidin-3-O-arabinoside needs to be further researched. In the present study, a UPLC-Q-TOF-MS-based metabomics approach was applied to reveal the metabolite changes and metabolic pathways in Caco-2 cells after cyanidin-3-O-arabinoside treatment. The results showed 10 differential metabolites between cyanidin-3-O-arabinoside treated and untreated Caco-2 cells. Especially, sphingosine, phosphoethanolamine, and taurine were found to be significantly altered in the Caco-2 cell after cyanidin-3-O-arabinoside treatment. A comparison of the Caco-2 cell group treated with cyanidin-3-O-arabinoside versus the control group (simvastatin) revealed seven identical metabolites, including uracil, pantothenate, cytidine, phosphatidylcholine (PC), γ-linolenic acid, dodecanoic acid, and myristic acid. Cyanidin-3-O-arabinoside could exert anti-tumor effects by inducing apoptosis, reducing cell membrane synthesis and energy metabolism, and triggering DNA damage. These results provide new insights into the anti-tumor mechanism of cyanidin-3-O-arabinoside on Caco-2 cells. [Display omitted] • Metabolomic characteristics of Caco-2 cells were revealed by UPLC-Q-TOF-MS. • The metabolic processes in Caco-2 cells were altered by Cyanidin-3-O-arabinoside. • Cyanidin-3-O-arabinoside and simvastatin had the same antitumor biomarker. • Cyanidin-3-O-arabinoside induced apoptosis, DNA and cell membrane damage. [ABSTRACT FROM AUTHOR]

A convenient method for highly diastereoselective synthesis of bexagliflozin 7a and its carbon-13 labeled analogue 7b was developed. The main feature is the stereoselective reduction of 16 catalyzed by BF 3 ·OEt 2 . Furthermore, the cocrystallization skill was firstly used for the purification of bexagliflozin and its analogue. The carbon-13 labeled bexagliflozin 7b was firstly prepared in five steps and in 57% overall chemical yield starting from the commercially available d -gluconolactone-[ 13 C 6 ]. [ABSTRACT FROM AUTHOR]

Aims Prostate cancer (PCa) is one of the most common cancers in men in the world. Advanced PCa, especially castration-resistant PCa (CRPC), is difficult to cure. There is an urgent need to develop novel agents for CPRC. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin and is a well-known antimalarial drug. DHA has been documented to be a potential anticancer agent for PCa. However, the mechanisms underlying the anticancer activity of DHA are still unknown. Main methods Proteomics analysis based on iTRAQ technology was performed to determine the protein profile changes in human prostate cancer PC3 cells treated by DHA, and apoptosis was detected by flow cytometry and transmission electron microscopy. Key findings DHA induced obvious apoptosis in PC3 cells. Using iTRAQ technology, we found 86 differentially expressed proteins linked to the cytotoxicity of DHA in PC3 cells. Gene ontology analysis showed the differentially expressed proteins were mainly associated with the protein synthesis and translation. Protein interaction network analysis and KEGG pathway analysis revealed altered aminoacyl-tRNA biosynthesis and metabolic pathways. Moreover, one candidate protein, heat shock protein HSP70 (HSPA1A), was identified by western blot analysis. Significance Our results indicate that multiple mechanisms involved in the anticancer activity of DHA in PC3 cells. Decreased HSP70 expression may have an important role in DHA-induced apoptosis in PC3 cells. Our data also provide novel insights into the anticancer mechanisms of DHA. [ABSTRACT FROM AUTHOR]

Cp ∗ Co(III)-catalyzed intermolecular C(sp 2 )–C(sp 3 ) assembly of (hetero)arenes with α-diazomalonates using a direct C–H functionalization logic was developed. A series of (hetero)arenes underwent alkylation efficiently under the assistance of pyrazolyl and pyrimidyl directing groups under relatively mild and operationally simple reaction conditions. Good functional group tolerance, satisfactory yields, and excellent regioselectivity were found. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is an infectious disease that poses a serious threat to human health. Rifampin (RIF) is an important first-line anti-TB drug, and rifampin resistance (RIF-R) is a key factor in formulating treatment regimen and evaluating the prognosis of TB. Compared with other drugs resistance, the RIF-R mechanism of Mycobacterium tuberculosis (M. tuberculosis) is one of the clearest, which is mainly caused by RIF resistance-related mutations in the rpoB gene. This provides a convenient condition for developing rapid detection methods, and also an ideal object for studying the general drug resistance mechanisms of M. tuberculosis. This review focuses on the mechanisms that influence the RIF resistance of M. tuberculosis and related detection methods. Besides the mutations in rpoB , M. tuberculosis can decrease the amount of drugs entering the cells, enhance the drugs efflux, and be heterogeneous RIF susceptibility to resist drug pressure. Based on the results of current researches, many genes participate in influencing the susceptibility to RIF, which indicates the phenomenon of M. tuberculosis drug resistance is very complex. [ABSTRACT FROM AUTHOR]

• An analytical model for shell-and-tube phase change thermal rectifier is derived. • The dynamic and static thermal rectification effects are analyzed and optimized. • The analytical solution can quickly and precisely predict the rectification effect. • The dynamic thermal rectification effect is patently higher than the static one. • Optimized dynamic and static rectification can be improved by 203.56 % and 33.56 %. Thermal rectification devices based on solid-liquid phase change material (PCM) can realize efficient and reversible control of forward and reverse heat flux. In this study, an analytical solution for a shell-and-tube phase change thermal rectifier is derived based on Fourier's law of heat conduction. The validity of the analytical model is confirmed by the numerical model verified by the exact solution of the single-phase Stefan problem. The influence of thermophysical properties, structural parameters, and initial temperature on the dynamic and static thermal rectification effects of the shell-and-tube heterojunction composed of polydimethylsiloxane (PDMS) and hexadecane (C16) is investigated and optimized. Results indicate that the proposed analytical model for the shell-and-tube phase change thermal rectifier enables rapid and precise prediction of thermal rectification effects. The presence of solid-liquid phases of C16 under forward and reverse heat transfer modes reduced the thermal resistance difference, resulting in poor initial rectification performance (only about 1.17). The optimized thermal rectification effect is significantly increased to 1.56, which is significantly improved by 33.56 %. Moreover, the dynamic rectification effect of the shell-and-tube thermal rectifier is notably higher than the static rectification effect. The average dynamic thermal rectification ratio within the first 50 s before and after optimization is 2.19 and 7.80, respectively, which is several times higher than the static thermal rectification ratio. This paper further analyzes the impact of initial temperature and finds that an increase in initial temperature can further enhance the dynamic thermal rectification effect. Raising the initial temperature to 5 K above the phase change temperature can increase the improvement of the dynamic rectification effect to 256.36 % in the first 50 s. The significance of this study lies in its potential to advance the understanding and practical application of thermal rectification based on PCM. [ABSTRACT FROM AUTHOR]

Versican, a large extracellular matrix proteoglycan, accumulates both in tumor stroma and cancer cells. It participates in cell adhesion, migration, and angiogenesis, all features of invasion and metastasis. However, the mechanism(s) whereby versican promotes cancer invasion and metastasis is not yet fully understood. A recent study has documented that versican can activate tumor-infiltrating myeloid cells through toll-like receptor (TLR) 2 and its co-receptors TLR6 and CD14 and elicit the production of proinflammatory cytokines including TNF-α that enhance tumor metastasis. As both resident fibroblasts and endothelial cells (ECs) also express functional TLR2 and its co-receptors, we hypothesized that, in addition to myeloid cells, versican may trigger the activation of both fibroblasts and ECs. Of interest, TLR2-mediated activation of EC and fibroblast has been observed to increase the secretion of interleukin-8, a proinflammatory CXC chemokine that potentiates neutrophil infiltration and angiogenesis, as well as metastatic growth. Ligation of TLR2 by versican appears to be directly involved in the activation of multiple types of cells in tumor stroma and the induction of inflammatory cytokine secretion, providing a link between inflammation and cancer metastasis. Accordingly, antagonists of versican and TLR2 restrain the activation of tumor stromal cells, which may offer a novel approach to cancer therapy by targeting tumor microenvironment. [Copyright &y& Elsevier]

Organic nanomaterials have made great progress in photothermal cancer cells therapy. However, it is still a challenge to synthesize self-assembled organic materials with good water dispersity and biocompatibility. Here, we designed near-infrared squaric acid derivatived nanoparticles as a versatile platform for tumor cells ablation. Such self-assembled organic nanaoparticles showed high photothermal conversion and strong PA signals, enabling the successful thermal abaltion of cancer cells. • NIR Asymmetric squaric acid dyes were synthesized and fabricated into nanomaterials by direct self-assemble process. • Strong NIR absorption and high photothermal conversion efficiency as well as strong PA signal could be afforded. • Successful photothermal ablation of cancer cells. [ABSTRACT FROM AUTHOR]