Search

Monochloropropanol esters (MCPDE) might pose a risk to human health are often present in thermally processed foods. The effect of 20 amino acids on the formation of MCPDE was examined in a palm oil model reaction. The findings indicated that glutamic and aminoadipic acids markedly enhance formation of MCPDE. Diacylglycerol was the primary precursor for MCPDE formation. Glutamic and aminoadipic acids could form five- or six-membered heterocycle compounds with diacylglycerol. The structures of these intermediates were identified using FT-IR spectra and LC-MS/MS. It is proposed that glutamic or aminoadipic acids reacts with glycerol diesters to form intermediates that promote formation of MCPDE. Our results provide a theoretical basis for the formation of MCPDE in thermal processing, which implies formation can be reduced by preventing contact between glutamate and glycerol esters. • Acidity or alkalinity of amino acids influenced the formation of MCPDE. • Glutamate and aminocaproic acid strongly promoted formation of MCPDE. • Five- or six-membered heterocycles were identified by FT-IR and LC-MS/TOF. [ABSTRACT FROM AUTHOR]

• Four new arylbenzofurans (1 - 4) were isolated from Veratrum nigrum. • Nine known compounds (5 - 13) were isolated and the structures were identified. • Compounds 1 - 3 , 5 , 7 - 9 and 11 - 13 showed anti-inflammatory activities. • Compound 5 and 6 showed anti-tumor activities on five tested cell lines. Four new arylbenzofurans, 2-(3′,5′-dimethoxy) phenyl-6-hydroxy-7-methoxy benzofuran (1, Neoveratrol A), 2-(3′-O- β -D-glucosyl-5′-hydroxy) phenyl-4,6-dimethoxy benzofuran (2 , Neoveratrol B), 2-(3′,5′-dimethoxy) phenyl-4-O- β -D-glucosyl-6-hyroxy benzofuran (3 , Neoveratrol C), 2-(3′,5′-dimethoxy) phenyl-6-hydroxy-7-O- β -D-glucosyl benzofuran (4 , Neoveratrol D), together with nine known ones (5-13) were isolated from the dried root and rhizome of a Traditional Mongolian medicinal herb Veratrum nigrum. The structures were elucidated by various spectroscopic methods including UV, IR, NMR and HR-MS. Among these compounds, 1 - 3 , 5 , 7 - 9 and 11 - 13 showed significant inhibitory effects on lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cells at the concentration ranging from 50.0–200.0 μ M. Compound 1 exhibited moderate activity against HepG2 and HCT-15. In addition, compound 5 and 6 showed inhibitory activities against human tumor cell lines HepG2, HCT-15, A549, MDA-MB-231 and SH-SY5Y with IC 50 range of 40–100 μ M. [ABSTRACT FROM AUTHOR]

Lactate serves not merely as an energy substrate for skeletal muscle but also regulates myogenic differentiation, leading to an elevation of reactive oxygen species (ROS) levels. The present study was focused on exploring the effects of lactate and ROS/p38 MAPK in promoting C2C12 myoblasts differentiation. Our results demonstrated that lactate increased C2C12 myoblasts differentiation at a range of physiological concentrations, accompanied by enhanced ROS contents. We used n-acetylcysteine (NAC, a ROS scavenger) pretreatment and found that it delayed lactate-induced C2C12 myoblast differentiation by upregulating Myf5 expression on days 5 and 7 and lowering MyoD and MyoG expression. The finding implies that lactate accompanies ROS-dependent manner to promote C2C12 myoblast differentiation. Additionally, lactate significantly increased p38 MAPK phosphorylation to promote C2C12 cell differentiation, but pretreatment with SB203580 (p38 MAPK inhibitor) reduced lactate-induced C2C12 myoblasts differentiation. whereas lactate pretreatment with NAC inhibited p38 MAPK phosphorylation in C2C12 cells, demonstrating that lactate mediated ROS and regulated the p38 MAPK signalling pathway to promote C2C12 cell differentiation. In conclusion, our results suggest that the promotion of C2C12 myoblasts differentiation by lactate is dependent on ROS and the p38 MAPK signalling pathway. These observations reveal a beneficial role for lactate in increasing myogenesis through ROS-sensitive mechanisms as well as providing new ideas regarding the positive impact of ROS in improving the function of skeletal muscle. [Display omitted] • Lactate promotes the differentiation of C2C12 cells. • Lactate promotes C2C12 cell differentiation in a ROS-dependent manner. • Lactate regulates C2C12 differentiation through the p38 MAPK signalling pathway. • ROS mediates the regulation of lactate on C2C12 cell differentiation through the p38 MAPK signalling pathway. [ABSTRACT FROM AUTHOR]

Functional fatigue—changes to the material response during cyclic loading—is a major barrier to the cycle lifetime demands of shape memory alloy technologies. Functional fatigue is caused by permanent changes to the microstructure such as the generation of dislocations during the forward and reverse martensitic phase transformation. In this work, far-field and near-field high-energy diffraction microscopy (ff- and nf-HEDM) are used to characterize the local accumulation of geometrically necessary dislocation (GND) density in the austenite phase in situ and in 3D across a bulk Ni 49.9 Ti 50.1 polycrystalline shape memory alloy during load-biased thermal cycling. A custom nf-HEDM data analysis procedure is used to reconstruct spatially-resolved intragranular misorientation maps that are then converted to spatially-resolved GND density maps. In this way, GND density is tracked in individual grains across cycles. We find that neither Schmid factor nor the maximum transformation work correlates strongly with GND density evolution during load-biased thermal cycling. The results show that the spatially-resolved GND density is distributed heterogeneously, but GND density increases faster near grain boundaries, in grains at the sample surface, and in grains with large volumes, indicating that these regions/types of grains will undergo different functional fatigue behaviors. Finally, the effect of grain neighborhood and grain boundaries on GND evolution are investigated, highlighting the role played by grain boundaries and the grain neighborhood in the evolution of GND density. This work demonstrates the utility of nf-HEDM for understanding the evolution of subgrain-scale plastic deformation, including materials that undergo a martensitic phase transformation. [Display omitted] [ABSTRACT FROM AUTHOR]

As an efficient lignocellulose fractionation process, peracetic acid and maleic acid (PAM) pretreatment is integrated into a multi-product platform for the simultaneous manufacture of cellulose, lignin, and xylose. Employing such strategy, 100 g corn stover (dry basis) yielded 39.63 g cellulose-rich solids along with 11.88 g xylose and 12.00 g lignin recovered from the pretreatment liquor. The recovery of xylose and lignin was assessed with various organic solvents, of which 2-methyltetrahydrofuran (2-MeTHF) showed superior performance, giving high lignin yield (75.23%) and xylose yield (67.32%). The recovered lignin (2-MeTHF-L) was characterized by high purity, relatively low molecular weight, and large numbers of carboxyl group. Besides, 2D-HSQC NMR analysis revealed that the 2-MeTHF-L was esterified with maleic acid during PAM pretreatment, partly responsible for its enhanced antioxidant ability. This strategy maximizes feedstock utilization and improves the processability in downstream valorization, offering a prospect for sustainable and efficient biorefineries. [Display omitted] • A multi-product strategy was evaluated for the fractionation of corn stover. • High lignin yield (75.23%) and xylose yield (67.32%) were attained with 2-MeTHF. • Recovered lignin possessed desirable properties such as low molecular weight. • Esterification of recovered lignin partly enhanced the antioxidant activity. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) play a key role in the presentation of tumor antigens to initiate innate and adaptive immune responses. While the tumor microenvironment (TME) contains a network of immunosuppressive factors that inhibit the differentiation and maturation of DCs. Immunoadjuvants have been focusing on modulating DCs function to improve cancer immunotherapy. Herein, a phenolic nanoadjuvant was developed by self-assembly of the sonosensitizer polymer (PEG-b-IR), GSH inhibitor (sabutoclax), Mn2+ and TME acidic sensitive phenolic polymer (PEG-b-Pho) via metal–phenolic coordination. The combinational action of SDT-mediated ICD effect and Mn2+ promoted the activation of the cGAS-STING pathway significantly enhanced DCs maturation. Furthermore, this phenolic nanoadjuvant greatly sensitizes tumors to PD-L1 checkpoint blockade immunotherapy, resulting in efficiently inhibiting the growth of distant tumors and restraining lung metastasis. Therefore, our work provides the potential to remedy the therapeutic limitation of insufficient antitumor immunity for enhanced cancer immunotherapy. The phenolic nanoadjuvant (PIMS NPs) promotes significant maturation of dendritic cells thereby sensitizes tumors to PD-L1 checkpoint blockade immunotherapy. After systemic injection of PIMS NPs, the low-intensity ultrasound applied on the primary tumor site is capable of eliciting ICD to release the TAAs and DAMPs. Meanwhile, the Mn2+ can be released in situ for enhancing the activation of the cGAS-STING pathway. The combinational action of SDT-mediated ICD and activation of the cGAS-STING pathway can significantly enhance the maturation of DCs. Furthermore, the activation of antitumor T cell immune responses can realize the potential of PD-L1 checkpoint blockade immunotherapy, which efficiently inhibits the growth of distant tumors and restrains lung metastasis. [Display omitted] • Sonodynamic therapy is a promising treatment that can elicit antitumor immunity by effectively killing tumor cells. • Mn2+ can promote the activation of the cGAS-STING pathway which significantly boosts the antitumor immunotherapy. • A phenolic nanoadjuvant is developed for stimulating the maturation of dendritic cells to induce the activation of T cells. • The enhanced DCs maturation can sensitize tumors to PD-L1 checkpoint blockade immunotherapy in an effective manner. [ABSTRACT FROM AUTHOR]

In this work, three indium tin oxide (ITO) films with distinct resistance values were realized by optimizing the deposition process, and X-ray photoelectron spectroscopy was performed to confirm the origin of resistance variation in the different ITO films. Three ITO/HfO x /TiN (IHT) devices were correspondingly constructed by capping the distinct ITO films applied as a top electrode. A series of reliability measures indicated that the IHT stack capping ITO films with high resistance value (R TE , ~600 Ω) demonstrated better performance. For example, endurance of up to 105 sweep cycles, compared with other stacks capping ITO films with low R TE (~300 Ω or 50 Ω). Furthermore, the Schottky emission mechanism was confirmed through fitting of I-V-curves in the HRS, and the carrier conduction was determined primarily by an Ohmic mechanism in the LRS. [ABSTRACT FROM AUTHOR]

Proteotoxic stress, caused by the accumulation of abnormal unfolded or misfolded cellular proteins, can efficiently activate inflammatory innate immune response. Initiating the mitochondrial proteotoxic stress might go forward to enable the cytosolic release of intramitochondrial DNA (mtDNA) for the immune-related mtDNA–cGAS–STING activation, which however is easily eliminated by a cell self-protection, i.e., mitophagy. In light of this, a nanoinducer (PCM) is reported to trigger mitophagy-inhibited cuproptotic proteotoxicity. Through a simple metal-phenolic coordination, PCMs reduce the original Cu2+ with the phenolic group of PEG-polyphenol-chlorin e6 (Ce6) into Cu+. Cu+ thereby performs its high binding affinity to dihydrolipoamide S-acetyltransferase (DLAT) and aggregates DLAT for cuproptotic proteotoxic stress and mitochondrial respiratory inhibition. Meanwhile, intracellular oxygen saved from the respiratory failure can be utilized by PCM-conjugated Ce6 to boost the proteotoxic stress. Next, PCM-loaded mitophagy inhibitor (Mdivi-1) protects proteotoxic products from being mitophagy-eliminated, which allows more mtDNA to be released in the cytosol and successfully stimulate the cGAS–STING signaling. In vitro and in vivo studies reveal that PCMs can upregulate the tumor-infiltrated NK cells by 24% and enhance the cytotoxic killing of effector T cells. This study proposes an anti-tumor immunotherapy through mitochondrial proteotoxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

Lactobacillus contribute to maintain the human healthy and use for nutritional additives as probiotics. In this study, a cholesterol-lowering bacterium, Lactobacillus gasseri TF08–1, was isolated from the feces of a healthy adolescent, and its probiotic potentials were evaluated through genomic mining and in vitro test. The assembled draft genome comprised of 1,974,590 bp and was predicted total of 1,940 CDSs. The annotation of the genome revealed that L. gasseri TF08–1 harbored abundant categories of functional genes in metabolic and information processing. Moreover, strain TF08–1 has capacity to utilize D -Glucose, Sucrose, D -Maltose, Salicin, D -Xylose, D -Cellobiose, D -Mannose, and D -Trehalose, as the carbon source. The safety assessment showed strain TF08–1 contained few antibiotic resistance genes and virulence factors and was only resistant to 2 antibiotics detected by antimicrobial susceptibility test. A high bile salt hydrolase activity was found and a cholesterol-reducing effect was determined in vitro , which the result showed a remarkable cholesterol removal capability of L. gasseri TF08–1 with an efficiency of 84.40 %. This study demonstrated that the strain showed great capability of exopolysaccharide production, and tolerance to acid and bile salt. Therefore, these results indicate that L. gasseri TF08–1 can be considered as a safe candidate for probiotic, especially its potential in biotherapeutic for metabolic diseases. • Analysis of metabolic end products revealed TF08-1 produced acetic acid, lactic acid, and succinic acid. • TF08-1 contained few antibiotic resistance genes and virulence factors. • Helveticin J, a bacteriocin gene cluster was detected in the genome of TF08-1. • TF08-1 was found to be high tolerant to acid and bile salt concentrations. • High bile salt hydrolase activity and cholesterol-lowering activity were determined by gene prediction and in vitro test. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a common and multiple endocrine metabolic disease. When pancreatic β cell in case of dysfunction, the synthesis and secretion of insulin are reduced. This study is to explore the effect of cordycepin (the molecular formula C 10 H 13 N 5 O 3), a natural adenosine isolated from Cordyceps militaris , on high glucose/lipid-induced glucotoxicity and lipotoxicity in INS-1 cells. Our results showed that cordycepin improved cell viability, improved cell energy metabolism and promoted insulin synthesis and secretion. The mechanism may be related to that cordycepin reduces intracellular reactive oxygen species (ROS), increases ATP content in cells, causes membrane depolarization and balances the steady state of Ca2+ concentration, cordycepin inhibits cell apoptosis, which may be related to the downregulation of proteins level of c-Jun N-terminal kinases (JNK) phosphorylation, cytochrome c (Cyt-c), Cleaved Capase-3, the mRNA level of JNK, Cyt-c, Capase-3 and upregulation of proteins/mRNA level of pancreatic and duodenal homeobox factor-1 (PDX-1). These results suggest that cordycepin can inhibit cell apoptosis and protect cell number by downregulating ROS/JNK mitochondrial apoptosis pathway under high glucose/lipid environment, thereby improving the function of pancreatic islet cells, providing a theoretical basis for the related research on the prevention and control of cordycepin on T2DM. [Display omitted] • Cordycepin protects INS-1 cells viability and energy metabolism against glucolipotoxicity. • Cordycepin inhibits INS-1 cells apoptosis exposed to a glucolipotoxicity environment. • Cordycepin improved insulin secretion and synthesis under glucolipotoxicity environment. [ABSTRACT FROM AUTHOR]

Cordycepin (known as 3-deoxyadenosine, CRD), a natural product from the valuable traditional Chinese medicine Cordyceps militaris , has been reported to improve cognitive function and modulate neuroprotective effects on the central nervous system (CNS). However, the modulating mechanisms of cordycepin on information processing in hippocampal CA1 pyramidal neurons are not fully understood. To clarify how cordycepin modulates synaptic responses of pyramidal neurons in rat hippocampal CA1 region, we conducted an electrophysiological experiment using whole-cell patch-clamp technique. The spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs, respectively) and the spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs, respectively) recorded by this technique evaluated pure single or multi-synapse responses and enabled us to accurately quantify how cordycepin influenced the pre and postsynaptic aspects of synaptic transmission. The present results showed that cordycepin significantly decreased the frequency of both glutamatergic and GABAergic postsynaptic currents without affecting the amplitude, while these inhibitory effects were antagonized by the A 1 adenosine receptor antagonist (DPCPX), but not the A 2A (ZM 241385), A 2B (MRS1754) and A 3 (MRS1191) adenosine receptor antagonists. Taken together, our results suggested that cordycepin had a clear presynaptic effect on glutamatergic and GABAergic transmission, and provided novel evidence that cordycepin suppresses the synaptic transmission through the activation of A 1 AR. [Display omitted] • Cordycepin decreased the frequency of glutamatergic postsynaptic currents. • Cordycepin decreased the frequency of GABAergic postsynaptic currents. • Cordycepin suppressed the synaptic transmission through the activation of A 1 AR. [ABSTRACT FROM AUTHOR]

A critical challenge remains in PD-1 checkpoint blockade immunotherapy is few tumor specific T cells infiltration in hypoxic tumor microenvironment (TME). Improving immunogenic cell death (ICD) associated immunogenicity can make tumor sensitive to PD-1 checkpoint blockade immunotherapy. Herein, a phenolic ICD inducer was engineered by self-assembly of the superior ICD inducer (doxorubicin, DOX), phenolic manganese dioxide nanoreactor, ferric iron and PEG-polyphenols (MDP NPs) via metal phenolic coordination. These oxygen self-supporting MDP NPs strengthen DOX based ROS-dependent cell death and their metal mediated chemodynamic effect accelerate ICD induction. Together with concomitant ICD triggered by DOX, MDP NPs successively lead to tumor-associated antigen boosting, DCs maturation and ultimately enhance tumor-specific T cells infiltration. Furthermore, MDP NPs efficiently modulated hypoxic TME for effective macrophages recruitment. This promising ICD-augment strategy efficiently improve tumor response to PD-1 checkpoint blockade immunotherapy, resulting in a significant antitumor immune response in primary tumor and a strong abscopal effect to distant tumor. Our simple and versatile phenolic inducer expands the application of chemodrugs based ICD enhancing PD-1 checkpoint blockade immunotherapy. [ABSTRACT FROM AUTHOR]