Racial Differences in Stage IV Colorectal Cancer Molecular Profiling and Mutation Rates.

INTRODUCTION: Despite advances in colorectal cancer (CRC) treatment, racial disparities persist. The primary aims of the study were to: evaluate differences in molecular testing rates over time by race; and measure the incidence of tumor mutations by race in patients with metastatic CRC. METHODS: A retrospective cohort study was performed of all adult patients with stage IV CRC (2008-2018) identified within the cancer registry of a large regional health system. Demographic/clinical characteristics were collected through primary data abstraction of the electronic health record. Molecular profiling results were obtained directly from Caris Molecular Intelligence and electronic health record. RESULTS: Three hundred eighty-three patients were included: 40.5% (n = 155) were Black and 59.5% (n = 228) were White. Significant increases were observed in microsatellite instability (MSI), KRAS, and BRAF testing rates during the study period (P < 0.0001). The odds of testing over time increased more significantly in Black compared to White patients for MSI testing (White: odds ratio [OR] 1.26 [95% confidence interval [CI] 1.12-1.41], Black: OR 1.69 [95% CI 1.41-2.02], P = 0.005) and BRAF testing (White: OR 1.42 [95% CI 1.26-1.62], Black: OR 1.89 [95% CI 1.51-2.36], P = 0.027). An increase in KRAS testing over time was observed for both cohorts and was independent of race (P = 0.58). Mutation rates did not differ by race: KRAS (Black 55.8% versus White 45.6%, P = 0.13) and BRAF (Black 4.8% versus White 10.0%, P = 0.33). CONCLUSIONS: Within a large regional health system, molecular testing rates in patients with metastatic CRC increased significantly following National Comprehensive Cancer Network guideline changes for both Black and White patients. Black and White patients who underwent molecular testing had similar rates of MSI, KRAS, and BRAF mutations.

The Effects of Foliar Supplementation of Silicon on Physiological and Biochemical Responses of Winter Wheat to Drought Stress during Different Growth Stages.

Drought is one of the major environmental stresses, resulting in serious yield reductions in wheat production. Silicon (Si) has been considered beneficial to enhancing wheat resistance to drought stress. However, few studies have explored the mediated effects of foliar supplementation of Si on drought stress imposed at different wheat growth stages. Therefore, a field experiment was carried out to investigate the effects of Si supplementation on the physiological and biochemical responses of wheat to drought stress imposed at the jointing (D-jointing), anthesis (D-anthesis) and filling (D-filling) stages. Our results showed that a moderate water deficit markedly decreased the dry matter accumulation, leaf relative water content (LRWC), photosynthetic rate (Pn), stomatal conductance (Sc), transpiration rate (Tr) and antioxidant activity [peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT)]. On the contrary, it remarkably increased the content of osmolytes (proline, soluble sugar, soluble protein) and lipid peroxidation. The grain yields of D-jointing, D-anthesis and D-filling treatments were 9.59%, 13.9% and 18.9% lower, respectively, compared to the control treatment (CK). However, foliar supplementation of Si at the anthesis and filling stages significantly improved plant growth under drought stress due to the increased Si content. Consequently, the improvement in antioxidant activity and soluble sugar, and the reduction in the content of ROS, increased the LRWC, chlorophyll content, Pn, Sc and Tr, and ultimately boosted wheat yield by 5.71% and 8.9%, respectively, in comparison with the non-Si-treated plants subjected to water stress at the anthesis and filling stages. However, the mitigating effect of Si application was not significant at the jointing stage. It was concluded that foliar supplementation of Si, especially at the reproductive stage, was effective in alleviating drought-induced yield reduction.

A-Lipoic Acid Alleviates Folic Acid-Induced Renal Damage Through Inhibition of Ferroptosis.

Folic acid (FA)-induced acute kidney injury (AKI) is characterized by the disturbance of redox homeostasis, resulting in massive tubular necrosis and inflammation. Α-lipoic acid (LA), as an antioxidant, has been reported to play an important role in renal protection, but the underlying mechanism remains poorly explored. The aim of this study is to investigate the protective effect of LA on FA-induced renal damage. Our findings showed that LA could ameliorate renal dysfunction and histopathologic damage induced by FA overdose injection. Moreover, FA injection induced severe inflammation, indicated by increased release of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-1ß, as well as infiltration of macrophage, which can be alleviated by LA supplementation. In addition, LA not only reduced the cellular iron overload by upregulating the expressions of Ferritin and ferroportin (FPN), but also mitigated reactive oxygen species (ROS) accumulation and lipid peroxidation by increasing the levels of antioxidant glutathione (GSH) and glutathione peroxidase-4 (GPX4). More importantly, we found that LA supplementation could reduce the number of Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive tubular cells caused by FA, indicating that the tubular cell death mediated by ferroptosis may be inhibited. Further study demonstrated that LA supplementation could reverse the decreased expression of cystine/glutamate antiporter xCT (SLC7A11), which mediated GSH synthesis. What is more, mechanistic study indicated that p53 activation was involved in the inhibitory effect of SLC7A11 induced by FA administration, which could be suppressed by LA supplementation. Taken together, our findings indicated that LA played the protective effect on FA-induced renal damage mainly by inhibiting ferroptosis.

Chemical profiling of Banxia-Baizhu-Tianma decoction by ultra-fast liquid chromatography with tandem mass spectrometry.

Banxia-Baizhu-Tianma decoction (BBTD) is a compound formulae of traditional Chinese medicine (TCM), which has been clinically used for treatments of neural vertigo, hypertension and epilepsy with a long history. In this study, with an ultra-fast liquid chromatography coupled with quadrupole time of flight mass spectrometry (UFLC-Q-TOF-MS) method, a total of 88 components in BBTD were identified by the accurate masses and fragmentation pathways including 19 flavonoids, 8 lactones, 12 triterpenoids, 10 phenolics, 14 amino acids, 13 nucleobases and nucleosides, 7 organic acids, and 5 other compounds. In addition, under the same chromatographic conditions, we developed an ultra-fast liquid chromatography coupled with quadrupole linear ion trap mass spectrometry (UFLC-Q-TRAP-MS) method to simultaneously quantify 20 bioactive components in multiple-reaction monitoring (MRM) mode. The assay method was validated in terms of linearity, precision, repeatability, recovery and was successfully applied for determination of 12 batches of BBTD. We hope that this study work would help to reveal the chemical profiling and provide a valuable and reliable approach for quality evaluation and even efficacy material basis study of BBTD.

Optimal Extraction Study of Gastrodin-Type Components from Gastrodia Elata Tubers by Response Surface Design with Integrated Phytochemical and Bioactivity Evaluation.

Gastrodia elata tuber (GET) is a popular traditional Chinese medicines (TCMs). In this study, response surface methodology (RSM) with a Box⁻Behnken design (BBD) was performed to optimize the extraction parameters of gastrodin-type components (gastrodin, gastrodigenin, parishin A, parishin B, parishin C and parishin E). Different from the conventional studies that merely focused on the contents of phytochemical, we gave consideration to both quantitative analysis of the above six components by HPLC and representative bioactivities of GET, including antioxidation and protection of human umbilical vein endothelial cells (HUVEC). Four independent variables (ethanol concentration, liquid-material ratio, soaking time and extraction time) were investigated with the integrated evaluation index of phytochemical contents. With the validation experiments, the optimal extraction parameters were as follows: ethanol concentration of 41%, liquid⁻solid ratio of 28.58 mL/g, soaking time of 23.91 h and extraction time of 46.60 min. Under the optimum conditions, the actual standardized comprehensive score was 1.8134 ± 0.0110, which was in accordance with the predicted score of 1.8100. This firstly established method was proved to be feasible and reliable to optimize the extraction parameters of the bioactive components from GET. Furthermore, it provides some reference for the quality control and extraction optimization of TCMs.

[Design and application of retention enema device].

OBJECTIVE: Drug retention enema is a common therapy for various illnesses. However, it is impossible to keep the drug in the colon for a long time, due to the limitation of the current equipment, and it is unable to achieve the purpose of retention enema. A retention enema device was designed by the department of intensive care unit (ICU) of Dongfeng Hospital Affiliated to Hubei University of Medicine. The retention enema device adds a spindle shaped inflatable air bag on the basis of the traditional enema device, which not only fix on the anus, but also prevent the leakage of enema fluid. It can achieve retention enema, play the enema drug effect fully, and significantly reduce the nursing workload, in addition, the silica gel material of the retention enema device ensures the comfort of the patients, the decompression air bag also avoids the damage of the high pressure of the spindle fixed air bag for the patients, which is worthy of clinical use.

Influence of acylglycerol emulsifier structure and composition on the function of shortening in layer cake.

The effect of the structure and composition of acylglycerol emulsifiers on the functionality of a palm-based shortening and quality of layer cake was investigated. The emulsifiers evaluated were distilled monoacylglycerol (DMG) and four acylglycerols (40% monoacylglycerol content) of octanoic acid (8:0), palmitic acid (16:0), stearic acid (18:0), and linoleic acid (18:2), designated as GMOct40, GMP40, GMS40, and GML40, respectively. The addition of GMP40 and GMS40 led to shortening with a higher solid fat content, finer crystals, and higher proportion of ß' form. These changes enhanced shortening's function in aiding air incorporation and retention in cake batter, which improved the cake's volume and crumb structure. However, the high monoacylglycerol content in DMG did not improve the properties of shortening and cake as compared to GMP40. In contrast, GML40 and GMOct40 had adverse effects on the functionality of shortening, which generated cakes with inferior crumb structure.

Draft genome sequence of the Tibetan medicinal herb Rhodiola crenulata.

Rhodiola crenulata, a well-known medicinal Tibetan herb, is mainly grown in high-altitude regions of the Tibet, Yunnan, and Sichuan provinces in China. In the past few years, increasing numbers of studies have been published on the potential pharmacological activities of R. crenulata, strengthening our understanding into its putitive active ingredient composition, pharmacological activity, and mechanism of action. These findings also provide strong evidence supporting the important medicinal and economical value of R. crenulata. Consequently, some Rhodiola species are becoming endangered because of overexploitation and environmental destruction. However, little is known about the genetic and genomic information of any Rhodiola species. Here we report the first draft assembly ofthe R. crenulata genome, which was 344.5 Mb (25.7 Mb Ns), accounting for 82% of the estimated genome size, with a scaffold N50 length of 144.7 kb and a contig N50 length of 25.4 kb. The R. crenulata genome is not only highly heterozygous but also highly repetitive, with ratios of 1.12% and 66.15%, respectively, based on the k-mer analysis. Furthermore, 226.6 Mb of transposable elements were detected, of which 77.03% were long terminal repeats. In total, 31 517 protein-coding genes were identified, capturing 86.72% of expected plant genes in BUSCO. Additionally, 79.73% of protein-coding genes were functionally annotated. R. crenulata is an important medicinal plant and also a potentially interesting model species for studying the adaptability of Rhodiola species to extreme environments. The genomic sequences of R. crenulata will be useful for understanding the evolutionary mechanism of the stress resistance gene and the biosynthesis pathways of the different medicinal ingredients, for example, salidroside in R. crenulata.

AMDE-1 is a dual function chemical for autophagy activation and inhibition.

Autophagy is the process by which cytosolic components and organelles are delivered to the lysosome for degradation. Autophagy plays important roles in cellular homeostasis and disease pathogenesis. Small chemical molecules that can modulate autophagy activity may have pharmacological value for treating diseases. Using a GFP-LC3-based high content screening assay we identified a novel chemical that is able to modulate autophagy at both initiation and degradation levels. This molecule, termed as Autophagy Modulator with Dual Effect-1 (AMDE-1), triggered autophagy in an Atg5-dependent manner, recruiting Atg16 to the pre-autophagosomal site and causing LC3 lipidation. AMDE-1 induced autophagy through the activation of AMPK, which inactivated mTORC1 and activated ULK1. AMDE-1did not affect MAP kinase, JNK or oxidative stress signaling for autophagy induction. Surprisingly, treatment with AMDE-1 resulted in impairment in autophagic flux and inhibition of long-lived protein degradation. This inhibition was correlated with a reduction in lysosomal degradation capacity but not with autophagosome-lysosome fusion. Further analysis indicated that AMDE-1 caused a reduction in lysosome acidity and lysosomal proteolytic activity, suggesting that it suppressed general lysosome function. AMDE-1 thus also impaired endocytosis-mediated EGF receptor degradation. The dual effects of AMDE-1 on autophagy induction and lysosomal degradation suggested that its net effect would likely lead to autophagic stress and lysosome dysfunction, and therefore cell death. Indeed, AMDE-1 triggered necroptosis and was preferentially cytotoxic to cancer cells. In conclusion, this study identified a new class of autophagy modulators with dual effects, which can be explored for potential uses in cancer therapy.