Genomic temporal heterogeneity of circulating tumour DNA in unresectable metastatic colorectal cancer under first-line treatment.

OBJECTIVE: Circulating tumour DNA (ctDNA) sequencing is increasingly used in the clinical management of patients with colorectal cancer. However, the genomic heterogeneity in ctDNA during treatments and its impact on clinical outcomes remain largely unknown. DESIGN: We conducted a prospective cohort study (NCT04228614) of 171 patients with unresectable metastatic colorectal cancer (mCRC) who underwent first-line treatment and prospectively collected blood samples with or without tumour samples from patients at baseline and sequentially until disease progression or last follow-up. RESULTS: The RAS/BRAF alterations in paired baseline tissue and plasma samples from 63 patients displayed a favourable concordance (81.0%, 51/63). After a period of first-line treatment (median time between baseline and last liquid biopsy, 4.67 months), 42.6% (26/61) of RAS-mutant patients showed RAS clearance and 50.0% (5/10) of BRAF-mutant patients showed BRAF clearance, while 3.6% (3/84) and 0.7% (1/135) of patients showed new RAS or BRAF mutations in ctDNA. Patients with plasma RAS/BRAF clearance showed similar progression-free survival (PFS) and overall survival (OS) with patients who remained RAS/BRAF wild-type, while much better outcomes than those who remained RAS/BRAF mutant. Patients who gained new RAS/BRAF mutations showed similar prognosis as those who maintained RAS/BRAF mutations, and shorter PFS and OS than those who remained RAS/BRAF wild-type. CONCLUSION: This prospective, serial and large-scale ctDNA profiling study reveals the temporal heterogeneity of mCRC-related somatic variants, which should be given special attention in clinical practice, as evidenced by the finding that the shift in plasma RAS/BRAF mutational status can yield a drastic change in survival outcomes.

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer.

INTRODUCTION: We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). METHODS: CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. RESULTS: Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. CONCLUSION: CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

A potential therapeutic agent for the treatment of hyperuricemia and gout: 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide.

Uric acid, the metabolic product of purines, relies on xanthine oxidase (XOD) for production. XOD is a target for the development of drugs for hyperuricemia (HUA) and gout. Currently, treatment options remain limited for gout patients. 3, 4-Dihydroxy-5-nitrobenzaldehyde (DHNB) is a derivative of the natural product protocatechualdehyde with good biological activity. In this work, we identify a DHNB thiosemicarbazide class of compounds that targets XOD. 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazone can effectively inhibit XOD activity (IC50 value: 0.0437 µM) and exhibits a mixed inhibitory effect. In a mouse model of acute hyperuricemia, a moderate dose (10 mg/kg.w) of 3,4-dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide effectively controlled the serum uric acid content and significantly inhibited serum XOD activity. In addition, 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide showed favorable safety profiles, and mice treated with the target compound did not show any symptoms of general toxicity following a single dose of 500 mg/kg. In the allopurinol group, 50 % of the mice died. These results provide a structural framework and mechanism of XOD inhibition that may facilitate the design of hyperuricemia and gout treatments.

A high level of integrin α6 expression in human intrahepatic cholangiocarcinoma cells is associated with a migratory and invasive phenotype.

BACKGROUND: The integrin α6 subunit is part of the integrin α6ß1 and α6ß4 complexes, which are known to mediate the invasion of carcinoma cells. However, the precise role of integrin α6 in intrahepatic cholangiocarcinoma (ICC) has not yet been addressed. METHODS: Twenty cases of ICCs and matched nontumor samples were used to analyze integrin α6 expression by immunohistochemistry. After the expression of integrin α6 was determined by RT-PCR and Western blot in ICC cells, we regulated the expression of integrin α6 in ICC cells with specific vshRNA-integrin α6, and assessed the role of integrin α6 in the proliferation and metastasis/invasion of ICC cells. Finally, the involved mechanisms and clinical significance were further investigated. RESULTS: The expression of integrin α6 in ICC tissues was much higher than that in nontumor samples, and the high level of integrin α6 was detected in ICC cells compared with normal liver cells and HepG2 cells. After the down-regulation of integrin α6 in HCCC-9810 cells, we showed that the ability of ICC cells to metastasize and invade was much decreased in vitro, and cell proliferation was inhibited significantly. Further study indicated high expression of integrin α6 enhanced the activation of ERK1/2 and AKT signals in ICC cells and the inhibition of ERK1/2 down-regulated ICC cell proliferation, while the inhibition of AKT markedly impaired ICC cell metastasis and invasion. Integrin α6 overexpression was significantly correlated with larger tumors, multiple nodular, microvascular/bile duct invasion, and lymphatic metastasis (p < 0.05). The postoperative 5-year overall survival (OS) rate in patients with integrin α6(low) was higher than that of the integrin α6(high) group. CONCLUSIONS: Overexpression of integrin α6 is associated with a migratory and invasive phenotype of ICC, and integrin α6 may be used as molecular target for therapy of ICC.

A high level of TM4SF5 is associated with human esophageal cancer progression and poor patient survival.

PURPOSE: We investigated expression of TM4SF5 and its involvement in human esophageal cancer (HEC). METHODS: We analyzed TM4SF5 expression in normal esophageal epithelial cells (HEEC), in four HEC cell lines, and in 20 HEC clinical tissue samples and matched nontumor samples. The effect of TM4SF5 on HEC cell proliferation and metastasis and invasion was assessed, and the relationship between TM4SF5 and integrin ß1 was determined. Finally, TM4SF5 and integrin ß1 expression were further examined by use of immunohistochemistry (IHC) and tissue microarray analysis, and the prognostic use of TM4SF5 and integrin ß1 in HEC was evaluated. RESULTS: TM4SF5 was more highly expressed in HEC cells and in HEC tissues than in HEEC and matched nontumor tissues. Down-regulation of TM4SF5 in KYSE150 cells reduced cell proliferation and metastasis and invasion whereas metastasis and invasion by KYSE510 increased after TM4SF5 cDNA transfection. In HEC cells, TM4SF5 formed a complex with integrin ß1, and interference with integrin ß1 in KYSE510-TM4SF5 cells markedly inhibited cell invasion on laminin 5. Our findings also showed that TM4SF5 and integrin ß1 overexpression correlated with low differentiation and high stage (p<0.05, respectively). Postoperative 5-year overall survival of patients with TM4SF5low and/or integrin ß1low was higher than for patients with TM4SF5high and/or integrin ß1high. Multivariate analysis demonstrated that TM4SF5 and integrin ß1 co-overexpression was an independent prognostic marker for HEC. CONCLUSION: TM4SF5 is positively associated with HEC invasiveness. The combination of TM4SF5 with integrin ß1 could potentially serve as a novel marker for predicting HEC prognosis.

Degradation of Zearalenone by Dielectric Barrier Discharge Cold Plasma and Its Effect on Maize Quality.

In this study, a dielectric barrier discharge (DBD) cold plasma was used to degrade zearalenone, and the degradation efficiency and the quality of maize were evaluated. The results showed that the zearalenone degradation rates increased with the increase in voltage and time. When it was treated at 50 KV for 120 s, the degradation percentage of the zearalenone in maize could reach 56.57%. The kinetics' analysis showed that the degradation followed a first-order reaction. The crude fiber of the maize reduced after the cold plasma treatment. In addition, cold plasma treatment did not significantly change the crude protein content, but slightly changed the fatty acid and color. The changes in maize quality are generally acceptable. DBD cold plasma may be a promising approach to reducing zearalenone in maize.

A study on the applicability of one-step vortex extraction and purification combined with gas chromatography-tandem mass spectrometry for analysis of four skin penetration enhancers in cosmetics.

Based on one-step vortex extraction and purification combined with gas chromatography-tandem mass spectrometry (GC-MS/MS), we established a simple, rapid, and efficient method for the simultaneous determination of four skin penetration enhancers in cosmetics, including isosorbide dimethyl ether, isopropyl myristate, N-butylsaccharin and Azone. The extraction procedure was performed in a centrifuge tube, allowing extraction and purification in a single step. The cosmetic sample was extracted by n-hexane-ethyl acetate (1:1, V/V), purified by silica gel and anhydrous magnesium sulfate as the solid phase purification agent, separated on a TG-5 ms column (30.0 m × 0.25 mm × 0.25 µ m), confirmed and detected by GC-MS/MS in the selected reaction monitoring (SRM) mode, and quantified by the internal standard method with Di-n­butyl phthalate-D4(DBP-D4) as the internal standard. The selections of a column, extraction solvent, and solid phase purification agent were optimized. Under the optimized conditions, the four skin penetration enhancers showed good linearities in the range of 0.02∼0.50 mg L - 1. The correlation coefficients (r) were 0.992 ∼ 0.997, exceeding the specifications requirements (r ≥ 0.990); The detection (LODs, S/N = 3) and quantification limits (LOQs, S/N = 10) of the method were 0.08 ∼ 0.12 mg kg-1 and 0.25 ∼ 0.40 mg kg-1, respectively. According to the cosmetic matrix in different formulation systems, the spiked recovery tests were carried out at three levels, i.e., low, medium, and high. The average recoveries of the analytes were 85.3% ∼ 95.6%, and the relative standard deviations (RSDs, n = 6) were 2.1% ∼ 7.8%. The established method was also employed to analyze cosmetics in the market. Azone, isosorbide dimethyl ether, and isopropyl myristate resulted as the most widely used skin penetration enhancers in cosmetics. The method established in this study has the advantages of operational simplicity, high sensitivity, good reproducibility, and low consumption of samples and solvents. Moreover, it can be used to determine skin penetration enhancers in cosmetics.

Effects of Lactobacillus casei NCU011054 on immune response and gut microbiota of cyclophosphamide induced immunosuppression mice.

Lactobacillus (L.) casei NCU011054 isolated from infant feces has been proven to be a potential probiotic in vitro. The present study aimed to investigate the effects of L. casei NCU011054 on the immune response and gut microbiota in cyclophosphamide (CP)-induced immunosuppression mice. Results indicated that L. casei NCU011054 could increase the levels of mucin (Muc2) and tight junction proteins (ZO-1, occludin and claudin-1). Moreover, L. casei NCU011054 was found to upregulate TLRs/NF-κB pathway (TLR-2, TLR-4, TLR-6, p65 and NF-κB) and two transcription factors (T-bet and GATA-3) mRNA levels, and enhance the number of CD4+T cells. Th1-related cytokines (IL-12p70, IFN-γ and TNF-α) and Th2-related cytokines (IL-2, IL-4, IL-6 and IL-10) significantly increased after L. casei NCU011054 treatment. More importantly, L. casei NCU011054 increased the ratio of T-bet to GATA-3 and IFN-γ to IL-4. Apart from these, L. casei NCU011054 remodeled gut microbiota and modulated gut metabolites in CP-induced immunosuppressed mice. The correlation analysis showed that Lactobacillus upregulated by L. casei NCU011054 was positively correlated with TLRs/NF-κB pathway, and the ratio of T-bet to GATA-3 and IFN-γ to IL-4. All findings revealed that L. casei NCU011054 could improve intestinal immune dysfunction and modulate Th1/Th2 balance via TLRs/NF-κB pathway in CP-induced immunosuppressed mice.

Exploring correlations between green coffee bean components and thermal contaminants in roasted coffee beans.

This study evaluated chemical compositions of green coffee beans from multi-production regions and correlated this information with thermal contaminants in roasted coffee. Using multivariate statistical techniques, formation of 5-hydroxymethylfurfural (5-HMF), furan, 2- and 3-methylfuran were positively correlated with lipid, sucrose, glutamic acid, phenylalanine, margaric acid, linolenic acid and trigonelline in green coffee beans. Moreover, significant positive correlations between acrylamide (AA) levels with aspartic acid, serine, alanine, histidine, asparagine, protein, and caffeine was found in green beans. Despite this, 5-HMF, furan, 2- and 3-methylfuran showed negative correlations with active constitutes (neochlorogenic acid, cryptochlorogenic acid, caffeine, total phenolics (TPC) and total flavonoids contents (TFC)), and several amino acids, and there were slight negative relationships between AA and myristic acid, palmitic acid, chlorogenic acid, sucrose, lipid, TPC and TFC. This study provides valuable enlightenment for the selection of proper coffee beans for production of coffee with high nutrition and low chemical hazardous risks.

Development of QuEChERS clean-up based on EMR-lipid for simultaneous analysis of 9 mycotoxins, acaylamide and 5-Hydroxymethylfurfural in biscuit by UHPLC-MS/MS.

A robust and sensitive analytical method for the simultaneous determination of 9 mycotoxins, AA, and 5-HMF by UHPLC-MS/MS was developed. Clean-up of the extracts was achieved by d-SPE with EMR-lipid. A new column phase (C18-PFP) was selected for HPLC separation after comparison with the C18 column. Finally, the method gave good linear relations with regression coefficients R2 > 0.99. The recovery of all the tested compounds was within the range of 70.67 to 104.88%, and the intraday and interday relative standard deviations (RSD) were lower than 12.49. The proposed method was then applied to investigate the mycotoxins, AA and 5-HMF in 20 food samples sold in the retail market. AA and 5-HMF were widely detected, and half of the samples were found to contain at least one mycotoxin contamination. Therefore, this method is potential to be used as a convenient and effective method for the cookies product quality control in the future.

Fabrication, characterization, and emulsifying properties of complex based on pea protein isolate/pectin for the encapsulation of pterostilbene.

In this study, pectin (PEC) and pea protein isolate(PPI) was successfully used to create complexes as a novel delivery system for pterostilbene (PT). When the mass ratio of PEC to PPI was 0.5, the particle size and ζ-potential of PPI-PEC-PT were 119.41 ± 5.68 nm and -23.26 ± 0.61 mV, respectively, and the encapsulation efficiency (EE) of PT was 90.92 ± 2.08%. The photochemical stability of PT was enhanced after encapsulation. The results of the molecular docking and multispectral analysis demonstrated that the PPI and PT binding was spontaneous and mostly fueled by hydrophobic interactions. The hydrophobicity of PPI was significantly decreased and the emulsification activity and emulsion stability were significantly improved after production with PEC and PT. The best emulsification impact was demonstrated by the PPI-PEC-PT complex. PPI-PEC is an effective PT delivery material, and the PPI-PEC-PT complex is a new functional emulsification material with significant potential in liquid and semi-liquid food and health products.

Residual circulating tumor DNA after adjuvant chemotherapy effectively predicts recurrence of stage II-III gastric cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context. METHODS: From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer-related genes. The plasma was defined as ctDNA-positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors. RESULTS: Compared with ctDNA-negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37-5.48; P = 0.003], while patients with positive post-ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08-72.96; P < 0.001). Multivariate analyses indicated that both postoperative and post-ACT ctDNA positivity were independent predictors of recurrence-free survival (RFS). Moreover, post-ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C-index (0.78; 95% CI = 0.71-0.84) than the model without ctDNA (0.71; 95% CI = 0.64-0.79; P = 0.009). CONCLUSIONS: Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue-based and circulating tumor features could achieve better risk prediction.

[Simultaneous determination of seven dimethylcyclosiloxanes in cosmetics of different formulation systems by gel permeation chromatography purification-gas chromatography-tandem mass spectrometry].

At present, the addition of dimethylcyclosiloxanes (DMCs) in cosmetics is being debated and no substantial progress has been made in their safety risk assessment because of the lack of a suitable analytical method. Therefore, it is of theoretical and practical significance to establish a method suitable for the determination of DMCs in cosmetics with different formulation systems. Accordingly, a method based on gel permeation chromatography (GPC) purification combined with gas chromatography-tandem mass spectrometry (GC-MS/MS) was developed for the determination of seven DMCs in cosmetics. The cosmetic samples were extracted by ethyl acetate-cyclohexane (1∶1, v/v), purified by gel permeation chromatography, separated on a DB-5ms column (30.0 m×0.25 mm×0.25 µm), confirmed and detected by gas chromatography-tandem mass spectrometry in the selected reaction monitoring (SRM) mode, and quantified by the internal standard method with n-hexadecane as the internal standard. Experiments were carried out using n-tetradecane, n-hexadecane, and n-octadecane as the internal standards, and based on the retention time in GPC and GC, n-hexadecane was found to be the suitable choice for further analyses. The extraction efficiency for the target compounds was tested in different solvents such as methanol, n-hexane, acetonitrile, ethyl acetate, and ethyl acetate-cyclohexane (1∶1, v/v). Given the high recovery, ethyl acetate-cyclohexane (1∶1, v/v) was selected as the extraction solvent for analyses. Among the three purification methods (analysis without purification, solid-phase extraction (SPE), and GPC purification), GPC was selected as the best method because of the minimal matrix interference to the target compounds. Under the optimized conditions, the seven DMCs showed good linearities in the range of 0.05-1.0 mg/L. The correlation coefficients (r) were 0.994-0.998, which were greater than the required of the specification (r≥0.990). The limits of detection (LODs, S/N=3) were 0.04-0.08 mg/kg, and the limits of quantification (LOQs, S/N=3) were 0.12-0.24 mg/kg. According to the cosmetic matrix in different formulation systems, standard addition recovery tests at three levels of low, medium, and high were carried out. The average recovery rates of the targets were 85.3%-108.8%. The relative standard deviations (RSDs, n=6) were 3.1%-9.4%. The established method was also employed for the analysis of cosmetics in the market, and octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) were detected at various levels in the cosmetics. The method established in this study has the advantages of operational simplicity, high sensitivity, and good reproducibility, and it allows for the determination of seven DMCs in cosmetics with different formulation systems. The establishment of this method provides a basis for the quality supervision and inspection of DMCs in cosmetics in China, in addition to providing technical support for follow-up health and safety evaluation.

Zearalenone Degradation by Dielectric Barrier Discharge Cold Plasma: The Kinetics and Mechanism.

In this study, dielectric barrier discharge (DBD) cold plasma was used to degrade zearalenone and the efficiency of degradation were evaluated. In addition, the degradation kinetics and possible pathway of degradation were investigated. The results showed that zearalenone degradation percentage increased with increasing voltage and time. When it was treated at 50 KV for 120 s, the degradation percentage could reach 98.28%. Kinetics analysis showed that the degradation process followed a first-order reaction, which fitted the exponential function model best (R² = 0.987). Meanwhile, liquid chromatographywith quadrupole time-of-flight mass spectrometry (Q-TOF LC/MS) was used to analyze the degradation products, one major compound was identified. In this study, the reactive species generated in cold plasma was analyzed by Optical Emission Spectroscopy (OES) and the free radicals were detected by Electron Spin Resonance (ESR). This study could provide a theoretical basis for the degradation of zearalenone to a certain extent.

Effects of baking factors and recipes on the quality of butter cookies and the formation of advanced glycation end products (AGEs) and 5-hydroxymethylfurfural (HMF).

Maillard reaction during food processing contributes to the formation of some unpleasant heat-induced toxicants including advanced glycation end products (AGEs) and 5-hydroxymethylfurfural (HMF), which have been linked to various health risks. The effects of baking factors and recipes, such as baking temperature (130°C-180 °C) and time (8 min-15 min), sucrose levels (0 g-20 g), butter levels (0 g-20 g) and egg liquid levels (0 g-12 g) on the formation of free Nε-(carboxymethyl)lysine (CML), free Nε-(carboxyethyl)lysine (CEL), protein-bound CML, protein-bound CEL, HMF, glyoxal (GO), methylglyoxal (MGO), 3-deoxyglucosone (3-DG) and on the sensory qualities were investigated in butter cookies. The results suggested that the levels of AGEs initially increased and then followed by decrease as baking temperature and time increased, HMF is very sensitive to baking temperature and time and grows sharply. The changes of protein-bound AGEs are lagging behind that of free AGEs. The proportions of sucrose, butter and egg liquid in butter cookies were positively correlated with AGEs, with sucrose greatly promoting on the formation of HMF and 3-DG. In addition, the high level of sucrose and butter in cookies is preferred by panelists, especially in terms of appearance, taste and smell.

Investigation of thermal contaminants in coffee beans induced by roasting: A kinetic modeling approach.

The roasting-induced formation of thermal contaminants in coffee beans, including 5-hydroxymethylfurfural (5-HMF), acrylamide (AA), furan (F), 2-methyl furan (2-MF), and 3-methyl furan (3-MF), was investigated using a kinetic modeling approach. Results showed that AA and 5-HMF formation and elimination occur simultaneously in coffee beans during roasting and that the related reactions follow first-order reaction kinetics. The concentrations of F, 2-MF, and 3-MF increased throughout the roasting experiment, and variations in the concentrations of these compounds during roasting could be best described by empirical, logistic model. The increase in weight loss and decrease in moisture content of the beans during roasting also displayed first-order reaction kinetics. High coefficients of determination (R2 > 0.981) were observed for all fitted models, and the reaction rate constants of all models followed the Arrhenius law.

Natural Antioxidants and Hydrocolloids as a Mitigation Strategy to Inhibit Advanced Glycation End Products (AGEs) and 5-Hydroxymethylfurfural (HMF) in Butter Cookies.

Maillard reaction during food processing contributes to the formation of some unpleasant heat-induced toxicants including advanced glycation end products (AGEs) and 5-hydroxymethylfurfural (HMF). The current study prepared butter cookies fortified with two dietary natural antioxidants (catechins and curcumin) and two dietary hydrocolloids (pectin and chitosan), and investigated their effects on formation of free Nε-(carboxymethyl)lysine (CML)/Nε-(carboxyethyl)lysine (CEL), protein-bound CML/CEL and HMF and on the sensory qualities of butter cookies. Meanwhile, three typical α-dicarbonyl compounds were also determined to identify possible correlations between α-dicarbonyl intermediates and formation of these harmful heat-induced products in butter cookies. Experimental data showed that catechin exhibited the strongest inhibitory effects on formation of AGEs and HMF, but its addition would impair the color and taste of cookies. On the other hand, chitosan was not so effective in inhibiting AGEs and HMF as compared to catechin, but its addition could increase the sensory qualities of butter cookies.

Effect of acidity regulators on acrylamide and 5-hydroxymethylfurfural formation in French fries: The dual role of pH and acid radical ion.

The influence of acidity regulators and buffers on the formation of acrylamide (AA) and 5-hydroxymethylfurfural (5-HMF) in French fries and the underlying mechanism were evaluated. Prior to frying, the potato strips were dipped in the corresponding acidity regulator solutions or buffers for 30 min at room temperature. The results showed that acids inhibited AA formation, but increased 5-HMF levels. The AA level decreased and 5-HMF level increased with decreasing pH of potato strips. Interestingly, increasing concentration of acid radical ions resulted in AA increase and 5-HMF decrease, which was opposite to the acidification effect of citric acid and acetic acid. Both pH and acid radical ion were important factors for AA and 5-HMF formation. Moreover, acidity regulators might impact AA formation by acting on the generation of methylglyoxal (MGO) and glyoxal (GO) and impact 5-HMF formation by acting on the generation of 3-deoxyglucosone (3-DG).

Maillard reaction harmful products in dairy products: Formation, occurrence, analysis, and mitigation strategies.

Various harmful Maillard reaction products such as lactulosyl-lysine (furosine), furfurals, and advanced glycation end products (AGEs) could be formed during the thermal processing of dairy products, which could lead to various chronic diseases. In this review, the furosine, furfurals, and AGEs formation, occurrence, analysis methods, and toxicological and health aspects in various dairy products were summarized to better monitor and control the levels of harmful Maillard reaction products in processed dairy products. It was observed that all types of dairy products, including raw milk, contain harmful Maillard reaction products, with the highest in whey cheese and condensed milk. High-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the common method for the determination of furosine and furfurals and AGEs in dairy products, respectively. However, the simple, rapid, environment-friendly, and accurate methods of determination are still to be developed. Incorporating resveratrol, pectin oligosaccharides (POS) in milk are effective methods to inhibit AGEs formation. This review provides a guide not only for consumers regarding the selection and consumption of dairy products, but also for monitoring and controlling the quality of dairy products.

Comprehensive profiling of 1015 patients' exomes reveals genomic-clinical associations in colorectal cancer.

The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST, DAPK1, CR2, KIF16B, NPIPB15, SYTL2, ZNF91, and KIAA0586. With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics, including hypermutated, chromosome instability with high risk, chromosome instability with low risk, and genome stability. Analysis of immunogenicity uncover the association of immunogenicity reduction with genomic subtypes and poor prognosis in CRC. Moreover, we find that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs. Overall, our results provide CRC-related molecular features for clinical practice and a valuable resource for translational research.