Extensive Analysis of Mulberry (Morus rubra L.) Polysaccharides with Different Maturities by Using Two-Step Extraction and LC/QqQ-MS.

A primary challenge of polysaccharide analysis is the need for comprehensive extraction and characterization methods. In this study, mulberry polysaccharides at different maturities were fully extracted through a two-step process involving ethylenediaminetetraacetic acid (EDTA) and sodium hydroxide (NaOH), and their structures were determined by a combination analysis of monosaccharides and glycosidic linkages based on liquid chromatography triple quadrupole mass spectrometry (LC/QqQ-MS). The results indicate mulberry polysaccharides mainly contain highly branched pectic polysaccharides, (1,3,6)-linked glucan, xylan, and xyloglucan, but the content of different portions varies at different maturity stages. HG decreases from 19.12 and 19.14% (green mulberry) to 9.80 and 6.08% (red mulberry) but increases to 17.83 and 11.83% as mulberry transitioned from red to black. In contrast, the contents of glucan showed opposite trends. When mulberry turns red to black, the RG-I arabinan chains decrease from 47.75 and 28.86% to 13.16 and 12.72%, while the galactan side chains increase from 1.18 and 1.91 to 8.3 and 6.49%, xylan and xyloglucan show an increase in content. Overall, the two-step extraction combined with LC/QqQ-MS provides a new strategy for extensive analysis of complex plant polysaccharides.

Yogurt Alleviates Imiquimod-Induced Psoriasis by Activating the Lactate/GPR81 Signaling Axis in Mice.

In addition to colorectal cancer and metabolic syndrome, regular yogurt consumption has shown promise in improving skin inflammation. In this study, we investigated the effects and possible mechanisms of yogurt on imiquimod-induced psoriasis-like inflammation in mice. After oral administration with yogurt (18 or 36 g/kg) and/or its main metabolite lactate (250 or 500 mg/kg) for 3 days, the mice were treated with a topical dose of 62.5 mg of imiquimod (IMQ) cream for seven consecutive days. Data showed that yogurt and lactate treatment significantly reduced the severity of psoriasis-like skin lesions, excessive keratinocyte proliferation, and immune cell infiltration. Mechanistically, we found that the genetic deficiency of the lactate receptor GPR81 aggravated psoriasis-like features in mice. Activation of the lactate/GPR81 axis inhibited the degradation of IκBα, prevented the nuclear translocation of histone deacetylase 3 (HDAC3) in macrophages, and thus constrained skin inflammation. Overall, these findings suggest that yogurt consumption effectively protects against experimental psoriasis and targeting the lactate/GPR81 signaling axis could be a promising approach for psoriasis inflammation management.

A metal ion-coordinated DNA probe for sensitive fluorescence detection of metallothionein via a dual nucleic acid amplification strategy.

Sensitively monitoring metallothionein (MT), a heavy metal-binding protein with substantial cysteine content, is of significance for evaluating heavy metal poisoning in both humans and animals. Based on a new metal ion-coordinated DNA probe and the heavy metal ion binding capability of MT, as well as the substantial signal enhancement of the hybridization chain reaction (HCR) and rolling circle amplification (RCA), we demonstrate a highly sensitive fluorescence MT detection assay. MT binds the metal ions in the hairpin structured, metal ion-coordinated DNA probe to switch its hairpin structure into ssDNA, which triggers subsequent RCA reactions and HCRs to open plenty of fluorescently quenched signal hairpins to exhibit drastically amplified fluorescence recovery for assaying MT down to 0.58 nM within a dynamic range of 1-320 nM. In addition, the investigation of low contents of MT in diluted human serum by such an assay has also been verified, indicating its promising application potential for diagnosing heavy metal poisoning.

Design and Parameter Identification for a Positioning Platform with a Large Stroke and High Precision for Segmented Mirrors.

An active optical system with three segmented mirrors was proposed to verify the co-focus and co-phase progress. In this system, a kind of large-stroke and high-precision parallel positioning platform was specially developed to help support the mirrors and reduce the error between them, which can move in three degrees of freedom out of plane. The positioning platform was composed of three flexible legs and three capacitive displacement sensors. For the flexible leg, a kind of forward-type amplification mechanism was specially designed to amplify the displacement of the piezoelectric actuator. The output stroke of the flexible leg was no less than 220 µm and the step resolution was up to 10 nm. Further, a linear model was established to identify the amplification ratio between the actuator and the flexible leg, which can increase the precision of the positioning platform. Moreover, three capacitive displacement sensors with a resolution of 2.5 nm were symmetrically installed in the platform to accurately measure the position and attitude of the platform. To improve the stability and precision of the platform, particle swarm optimization algorithm was applied to identify the control matrix, which can help the platform achieve ultra-high precision positioning. The results showed that the theoretical matrix parameters had a maximum deviation of 5.67% from the experimental ones. Finally, abundant experiments verified the excellent and stable performance of the platform. The results proved that while bearing the heavy mirror, which is no more than 5 kg, the platform can realize a 220 µm translation stroke and 2.0 mrad deflection stroke, with a high step resolution of 20 nm and 0.19 µrad. These indicators can perfectly cater to the requirements of the proposed segmented mirror system's co-focus and co-phase adjustment progress.

Cancer-associated fibroblasts facilitate DNA damage repair by promoting the glycolysis in non-small cell lung cancer.

Radiotherapy is an essential treatment modality for the management of non-small cell lung cancer (NSCLC) patients. Tumor radioresistance is the major factor limiting the efficacy of radiotherapy in NSCLC patients. Our study aimed to reveal whether cancer-associated fibroblasts (CAFs), one main component of the tumor microenvironment, regulated DNA damage response of NSCLC cells following irradiation and clarify the involved mechanisms. We found CAFs inhibited irradiation-induced DNA damage while promoted DNA repair of NSCLC cells and caused cell cycle arrest in the radioresistant S phase. CAFs have the ability of up-regulating and stabilizing c-Myc, leading to the transcription activation of HK2 kinase, a key rate-limiting enzyme in glycolysis by activating Wnt/ß-catenin pathway. Attenuation of glycolysis significantly reversed the effect of CAFs on DNA damage response of NSCLC cells. By high-throughput screening of human cytokines/chemokines array, we found CAFs-secreted midkine led to the promotion of glycolysis by activating Wnt/ß-catenin pathway in NSCLC cells. In vivo, CAFs caused the radioresistance of NSCLC cells also by promoting the glycolysis in a ß-catenin signaling-dependent manner. These findings may provide novel strategies for reversing the radioresistance of NSCLC cells.

Aspirin Suppresses Hepatic Glucagon Signaling Through Decreasing Production of Thromboxane A2.

Excessive hepatic glucose production (HGP) is a major cause of fasting hyperglycemia in diabetes, and antihyperglycemic therapy takes center stage. Nonsteroidal anti-inflammatory drugs, such as acetylsalicylic acid (aspirin), reduce hyperglycemia caused by unrestrained gluconeogenesis in diabetes, but its mechanism is incompletely understood. Here, we reported that aspirin lowers fasting blood glucose and hepatic gluconeogenesis, corresponds with lower thromboxane A2 (TXA2) levels, and the hypoglycemic effect of aspirin could be rescued by TP agonist treatment. On fasting and diabetes stress, the cyclooxygenase (COX)/TXA2/thromboxane A2 receptor (TP) axis was increased in the livers. TP deficiency suppressed starvation-induced hepatic glucose output, thus inhibiting the progression of diabetes, whereas TP activation promoted gluconeogenesis. Aspirin restrains glucagon signaling and gluconeogenic gene expression (phosphoenolpyruvate carboxykinase [PCK1] and glucose-6-phosphatase [G6Pase]) through the TXA2/TP axis. TP mediates hepatic gluconeogenesis by activating PLC/IP3/IP3R signaling, which subsequently enhances CREB phosphorylation via facilitating CRTC2 nuclear translocation. Thus, our findings demonstrate that TXA2/TP plays a crucial role in aspirin's inhibition of hepatic glucose metabolism, and TP may represent a therapeutic target for diabetes.

Cancer-associated fibroblasts: An emerging target against esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. More than 70% of ESCC patients are diagnosed at the intermediate or advanced stage. Concurrent chemoradiotherapy is the standard treatment regimen for patients with advanced ESCC. However, ESCC patients show a poor 5-year survival rate of around 20%. Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and control tumor initiation and progression. CAFs create a pro-survival and immunosuppressive microenvironment by crosstalk with cancer cells. Moreover, CAFs lead the collective invasion of cancer cells of the epithelial phenotype by remodeling the extracellular matrix. In this review, we highlight the impact of CAFs on ESCC, including induction of chemo- and radio-resistance, migration, invasion, and immune escape. The origin of CAFs and the influence of ESCC cells on CAF activation are also described. Furthermore, we highlight the clinical prospects and future trends of CAFs-targeted therapies in ESCC. A better understanding of the molecular biology of CAFs may contribute to the development of novel anti-ESCC strategies.

Oyster (Crassostrea gigas) Polysaccharide Ameliorates High-Fat-Diet-Induced Oxidative Stress and Inflammation in the Liver via the Bile Acid-FXR-AMPKα Pathway.

Oyster polysaccharides (OPS) have a variety of biological activities. In this study, we aimed to investigate the potential mechanisms of OPS to ameliorate hepatic oxidative stress and inflammation in mice induced by a high-fat diet (HFD). The results showed that OPS reduced the HFD-induced increases in serum transaminase levels and alleviated hepatic oxidative stress and inflammation. Moreover, OPS regulated bile acid metabolism and increased bile acid content in the liver, serum, and feces. Serum bile acid profile results indicated that OPS reduced levels of chenodeoxycholic acid, deoxycholic acid, and lithocholic acid associated with high-affinity agonists of Farnesol X receptor (FXR). Western blot analysis showed that OPS accelerated bile acid metabolism by downregulating hepatic FXR expression and promoting its downstream CYP7A1, CYP27A1, and CYP8B1 protein expression. Meanwhile, OPS ameliorated oxidative stress and inflammation in the liver by modulating FXR-AMPKα-Nrf2/NF-κB signaling to reduce p-IκBα/IκBα, p-NF-κB p65/NF-κB p65, IL-1ß, and TNF-α expression and increase p-Nrf2/Nrf2, HO-1, and NQO-1 expression. This study was the first to explore the possible mechanism of OPS in improving liver oxidative stress and inflammation from the perspective of bile acid metabolism, providing a theoretical basis for OPS as a new source of functional food.

Measurement of internal stray radiation of a thermal infrared spectrometer based on temperature variation.

The level of internal stray radiation is an important criterion to evaluate the performance of a thermal infrared spectrometer. In this study, a novel method is proposed and evaluated to measure the internal stray radiation of a thermal infrared spectrometer based on temperature variation. The proposed method was used to measure the internal stray radiation values of an existing instrument. First, two output gray value curves were constructed for a single spectral channel in a cryogenic detector at two different spectrometer temperatures based on radiometric calibration measurements. Subsequently, the gray value and radiation flux of the internal stray radiation of the spectrometer were calculated. In addition, the internal stray radiation data measured at different spectral channels and different integration times were used to verify and evaluate the proposed method. Results show that the proposed method is valid, and the standard deviations of the various internal radiation values of the tested spectral channels and the various integration times are 3.47% and 1.46%, respectively. The proposed method is adaptable, flexible, and efficient.