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Abstract Conjugated linolenic acid (CLnA) is a mixture of octadecenoic acid with multiple positional and geometric isomers (including four 9, 11, 13-C18:3 isomers and three 8, 10, 12-C18:3 isomers) that is mainly present in plant seeds. In recent years, CLnA has shown many promising health benefits with the deepening of research, but the metabolic characteristics, physiological function differences and mechanisms of different isomers are relatively complex. In this article, the metabolic characteristics of CLnA were firstly reviewed, with focus on its conversion, catabolism and anabolism. Then the possible mechanisms of CLnA exerting biological effects were summarized and analyzed from its own chemical and physical characteristics, as well as biological receptor targeting characteristics. In addition, the differences and mechanisms of different isomers of CLnA in anticancer, lipid-lowering, anti-diabetic and anti-inflammatory physiological functions were compared and summarized. The current results show that the position and cis-trans conformation of conjugated structure endow CLnA with unique physical and chemical properties, which also makes different isomers have commonalities and particularities in the regulation of metabolism and physiological functions. Corresponding the metabolic characteristics of different isomers with precise nutrition strategy will help them to play a better role in disease prevention and treatment. CLnA has the potential to be developed into food functional components and dietary nutritional supplements. The advantages and mechanisms of different CLnA isomers in the clinical management of specific diseases need further study. [ABSTRACT FROM AUTHOR]

Simple Summary: At a genomic level metastatic castrate resistant prostate cancer state is highly heterogeneous and no clear genome-based prognostic or predictive biomarkers exist in practice. We evaluated multiple copy number somatic alterations in two castrate resistant patient cohorts to determine if a genome-based risk score at the copy number level can predict clinical outcomes. The first cohort included patients in a prospective clinical-trial in which abiraterone acetate was given and the other comprised of a real-world hospital-registry. We extracted plasma cell free DNA in both cohorts and performed low pass whole genome sequencing. Copy number alterations were identified for 24 candidate genes and a final composite score developed from 11 genes. This risk score was able to predict survival in castrate resistant patients after adjusting for known clinical biomarkers. Additionally, the multi-gene copy number alteration based risk score algorithm also predicted if abiraterone acetate would be effective in castrate resistant patients. A plasma cell-free DNA (cfDNA) multi-gene copy number alteration (CNA)-based risk score was evaluated to predict clinical outcomes in metastatic castrate resistant prostate cancer (mCRPC) patients. Methods: Plasma specimens from two independent mCRPC patient cohorts (N = 88 and N = 92 patients) were used. A treatment-naïve mCRPC cohort (prospective clinical-trial cohort) included plasma samples before treatment with abiraterone acetate/prednisone and serially at 3-months. A separate real-world hospital-registry (RWHR) mCRPC cohort included a single blood sample collected prior to mCRPC treatments in 92 mCRPC patients following ADT failure. Low pass whole genome sequencing was performed on plasma cell-free DNA (cfDNA) and copy number alterations (CNAs) were identified for 24 candidate genes of interest. Associations of individual gene CNAs with 3 month primary resistance to therapy, progression-free survival (PFS) in the prospective trial cohort and overall survival (OS) in both cohorts was evaluated by Cox regression. A multi-gene risk score was determined for significantly associated candidate CNAs for predicting clinical outcomes. Clinical factors were included in the risk model for survival. Statistical significance for all tests was set at 0.05. Results: In the prospective trial cohort, patients responding to treatment were observed to have a significant copy number decrease in AR (p = 0.001) and COL22A1 (p = 0.037) at 3 months, while the non-responder group showed a significant CNA decrease in NKX3.1 (p = 0.027), ZBTB16 (p = 0.025) and CNA increases in PIK3CB (p = 0.006). Based on the significance level of each gene, CNAs in 11 of the 24 genes (AR, COL22A1, MYC, NCOR1, NKX3.1, NOTCH1, PIK3CA, PIK3CB, TMPRSS2, TP53, ZBTB16) were selected to develop a Cox-regression coefficient-based weighted multi-gene risk score for predicting mCRPC outcomes in both cohorts. A higher multi-gene risk score was observed to have poor OS in mCRPC patients in the prospective trial cohort (p = 0.00019) and for the RWHR cohort, (p < 0.0001). A higher risk score was also associated with poor PFS in the prospective cohort (p = 0.0043). Conclusions: A multi-gene CNAs-based risk score derived from plasma cfDNA may predict treatment response and prognosticate survival in mCRPC and warrants prospective validation of risk-based algorithms. [ABSTRACT FROM AUTHOR]

Torreya grandis seed oil, with a feature of Δ5‐sciadonic acid (SA, 20:3 Δ5, 11, 14 ω‐6), is an attractive woody oil as its potential health benefits in lowering blood and hepatic lipids and anti‐inflammatory properties. In the present study, its oxidative stabilities at both room temperature and heating conditions were investigated by analysing oxidation stability index (OSI), shelf‐life, changes of fatty acids, acid value and peroxide value during stir‐frying tests. Also, its effects on the sensory qualities of stir‐fried shredded potatoes were evaluated. The OSI of T. grandis seed oil was 2.97 h at 120 °C, which was 11.24% higher than that of the control soybean oil, contributing to a longer predicted shelf‐life of 135–195 d for T. grandis seed oil than 127–180 d for soybean oil. T. grandis seed oil also exhibited superior thermal stability compared to soybean oil. The feature fatty acid, SA, only lost 2.48–5.73% (decreasing from 14.14 to 13.33–13.79%) under the optimised stir‐frying conditions at 140–180 °C for 3–5 min. For the stir‐frying shredded potatoes, T. grandis seed oil made it more pleasing in colour, odour and palatability. Due to its desirable oxidative stability at room temperature and stir‐frying performance at high temperature, T. grandis seed oil is suitable for use as a domestic cooking oil. [ABSTRACT FROM AUTHOR]

Rhizome rot and quality deterioration of tender ginger after harvest were the restricting factors of tender ginger storage quality. In this research, cold storage with SO2 fumigation function was designed and the effects of 0.2, 0.5, and 1.0 ml L−1 SO2 fumigation every 15 d on the storage quality of tender ginger was investigated. The improved cold storage and supporting equipment can automatically fill and remove SO2 gas into the storage room, and keep the humidity stable at 92%–95% during storage. Experimental results showed that automatic periodical SO2 fumigation of tender ginger with 0.5 ml L−1 SO2 every 15 d can effectively maintain firmness (~56%), retard weight loss (~22%), reduce decay rate (~20%), and inhibit the accumulation of malondialdehyde (MDA) content (~26%). Meanwhile, the 0.5 ml L−1 SO2 treatment enhanced the disease resistance of tender ginger by enhancing phenylalanine ammonia lyase (PAL) activity (~8%) and inhibiting polyphenol oxidase (PPO) activity (~25%), and the integrity of tissue structure was also well maintained. More importantly, the SO2 residue in the tender ginger treated with the 0.5 ml L−1 SO2 completely met the FDA food safety standard on the 50 d. Therefore, the combination of cold storage structure innovation and 0.5 ml L−1 SO2 periodical fumigation is more effective at improving the storage quality of tender ginger. Practical applications: Automatic periodical SO2 fumigation showed great potential application in maintaining the storage quality of ginger after harvest. The activity levels of defense enzymes were significantly increased and the storage quality of tender ginger was well maintained. Automatic periodical fumigation of tender ginger with 0.5 ml L−1 SO2 is a simple, safe, low cost, and convenient method to improve the storage quality of tender ginger. [ABSTRACT FROM AUTHOR]

Objectives To identify genomic variations in cell-free DNA (cfDNA) and evaluate their clinical utility in small cell lung cancer (SCLC). Materials and methods We performed whole genome sequencing using plasma cfDNAs derived from 24 SCLC patients for copy number variation (CNV) analysis, and targeted sequencing using 17 pairs of plasma cfDNA and their matched gDNA for mutation analysis. We defined somatic mutations by comparing cfDNA to its matched gDNA with 5% variant alleles as the cutoff for mutation calls. We applied Kaplan-Meier to correlate the genomic alterations with overall survival (OS) and progression-free survival (PFS). Results We observed widespread somatic copy-number alterations and mutations, including amplification of MYC at 8q24, FGF10 at 5p13, SOX2 at 3q26 and FGFR1 at 8p12, as well as deletion of TP53 at 17p13, RASSF1 at 3p21.3, RB1 at 13q14.2, FHIT at 3p14, and PTEN at 10q23. The most frequent mutations were genes involved in chromatin regulation ( KMT2D , ARID1A , SETBP1 and PBRM1) , PI3K/MTOR pathway( MTOR , PIK13G ), Notch1 signalling pathway ( NOTCH1 ), and DNA repair related gene ATRX . Kaplan-Meier analysis revealed poor OS and PFS in patients with somatic mutations in gene SETBP1 (P = 0.0061/0.0264, HR = 4.785/3.841, 95% CI = 2.014–28.25/1.286–16.58) and PBRM1 (P = 0.0276/0.0286, HR = 3.532/3.506, 95% CI = 1.275 to 25.34/1.26–24.87). Poor OS was also associated with somatic mutations in ATRX (P = 0.0099, HR = 4.024, 95% CI = 1.926–42.95), EP300 (P = 0.025/0.0622, HR = 3.382/2.891, 95% CI = 1.448–27.76/1.013-17.29), while poor PFS was associated with ATM mutation (P = 0.0038, HR = 4.604, 95% CI = 2.211–40.93). The mutation index produced by summing up the number of mutations in the five genes was significantly associated with the poor OS/PFS (P = 0.0185/0.0294) after adjusting the effect of the stage. Conclusions Our result supports blood plasma as a promising sample source for the genomic analysis in SCLC patients whose tumor tissues are scarcely available and demonstrates potential clinical utilities of cfDNA-based liquid biopsy for clinical management of this deadly disease. [ABSTRACT FROM AUTHOR]

R5762 --> 484.10 --> Kras is one of the most frequently mutated genes in pancreatic cancer, with the G12D variant acting as a cancer driver mutation. Our previous work has integrated and defined gene networks induced by KrasG12D expression, particularly the expression of inflammatory gene clusters. Moreover, we observed that KrasG12D expression increases the overall protein levels of several histone marks, including H3K4me3, H3K27ac, H3K27me3, H3K9me3 and integrated data analysis correlated gene activation and silencing with the alteration of histone marks. Here we further consider KrasG12D‐driven changes in gene expression and hypothesize that G9a‐H3K9me2 may play an important role in the epigenomic regulation of this process. To investigate epigenomic mechanisms underlying KrasG12D‐induced gene expression networks, CUT&RUN technology was used to profile H3K4me3 (promoter), H3K9ac (promoter, enhancer), H3K27ac (enhancer, super‐enhancer), and H3K9me2 (silencer) histone marks at regulatory elements. We used a genetically engineered mouse model (GEMM)‐derived inducible KrasG12D cell line and compared the epigenetic changes after 24hr of oncogene induction. Data was analyzed by using Sparse Enrichment Analysis for CUT&RUN (SEACR). At the genomic level, we found most H3K4me3 peaks (~90%) were close to a transcription start site (TSS), and the number of H3K4me3 peaks were reduced ~9x after KrasG12D activation. However, for the gene silencing mark, H3K9me2, >80% peaks were located at intronic or inter‐genetic regions, and the number of peaks were increased >5x with KrasG12D. For H3K9ac and H3K27ac histone marks, we observed more peaks at intronic or inter‐genetic regions than at the TSS, indicating the exchange of histone marks at enhancer, super‐enhancer and silenced regions may play an important role in KrasG12D‐induced gene expression changes. We next focused on histone modifications at regulatory elements of inflammatory gene clusters, such as IL11, CXCL9‐CXCL10‐CXCL11, and IL4‐IL13 gene clusters. We further correlated epigenetic modifications with our gene expression data and found that the H3K4me3, H3K9ac, and H3K27ac, and H3K9me2 histone mark pathways are involved in the regulation of these inflammatory genes. Notably, these pathways are both, critical for pancreatic cancer development and potentially druggable, and therefore, these results bear both mechanistic and biomedical relevance to pancreatic carcinogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Ancient DNA methodologies can be applied in the investigation of the genetics of extinct populations. A search for beta thalassemia mutations was performed on 49 Minoan individuals from the Bronze Age who were living in the island of Crete approximately 4000Years Before Present (YBP). Standard precautionary measures were employed in the laboratory to ensure authenticity of the DNA extracted from the ancient bones, resulting in the successful analysis of DNA of 24 Minoans. DNA sequencing focused on the Intervening Sequence 1 (IVS-1) of the beta globin gene and its splicing junctions. 63% of the thalassemia mutations observed among modern Cretans reside in beta IVS-1. None of the Minoan individuals carried one of the IVS-1 mutations known to cause beta thalassemia; however, only one was expected to be observed if the average frequency of beta thalassemia heterozygotes in the Minoan population was the same with that of modern day Cretans (7.6%). One individual contained a C to G substitution in position 91 of the IVS-1, located 40bp 5′ to the intron 1/exon 2 junction. Functional studies indicated that the mutation did not affect mRNA splicing or stability, and most likely represented an innocent single nucleotide polymorphism. [Copyright &y& Elsevier]

• 1% and 3% CO 2 pulsed controlled atmosphere can delay the loss of fruit water-core • There is the best effect of 1% CO 2 on maintaining the overall visual and sensory quality of fruit • The endurance of watercored apples to 5% CO 2 is less than 45 days • The internal browning of fruit is related to unstable membrane system and dense cell arrangement Watercored 'Fuji' apple with special water core and unique flavor is a characteristic fruit. However, the problems of water core disappearance and browning in the apples are outstanding during postharvest storage. In this study, pulsed controlled atmosphere (pCA) with CO 2 was used to protect the water-core and resist browning of apples. Effects of different concentrations of CO 2 on the quality of apple fruits was investigated, and CO 2 injury characteristic to apple fruits were studied as well. Results showed that pCA with CO 2 could effectively maintain the sensory and texture qualities of watercored apples. Treated with pulsed controlled CO 2 , the degree of membrane lipid peroxidation of the apples was effectively reduced and the membrane system was well maintained. Meanwhile, the activity of polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL) of the apples were inhibited and the browning was reduced. On the whole, pCA with 1% CO 2 presented the most significant effects on the quality preservation of watercored apples while higher CO 2 showed negative effects on the quality of the samples. Under the condition of pCA with 5% CO 2 , the endurance of watercored apples was less than 45 days and the internal browning was serious. In conclusion, 2%～3% O 2 and pCA with 1% CO 2 was the best and most effective in the long-term preservation of watercored apples, and it is beneficial to guide for the preservation of apple fruits. [ABSTRACT FROM AUTHOR]

• Litchi peel extract (LPE) was characterized by LC–MS/MS. • CS, nano-TiO 2 and LPE were used to develop active packaging films and coatings. • Nano-TiO 2 and LPE influenced films' physical, mechanical and structural properties. • CTL coating effectively maintained the storage quality of Fuji watercored apples. Nano-titanium dioxide (nano-TiO 2) and litchi peel extract (LPE) were added to chitosan (CS) matrix to develop a novel active packaging film and watercored apple coating. The addition of nano-TiO 2 and/or LPE enhanced mechanical strength, water vapor barrier properties, and thermal stability of CS-based films. The total phenolic content and antioxidant capacity of the films were enhanced by LPE incorporation. Viscosity and wettability of the coating solutions and their impact on the storage quality of watercored Fuji apples at 0 ± 1℃ for 180 d were investigated. Coating treatment significantly inhibited respiration rate, weight loss, and softening. Polyphenol oxidase activity, electrolyte leakage and malondialdehyde accumulation were inhibited by coating treatment. A CS + TiO 2 +LPE coating was the most effective treatment for maintaining cold storage quality of watercored apples. This combination presents promising applications as an active food packaging film and fruit preservation coating. [ABSTRACT FROM AUTHOR]

The postharvest decay of durian (Durio zibethinus Murr.) increases rapidly when the storage time is extended, which seriously limits the commercial value. In this research, the effects of appropriate periodical SO2 fumigation and different CO2‐enriched atmospheres (3% O2 + 10%–13%, 14%–17%, or 18%–21% CO2) on the storage quality of durian stored at 14°C were investigated. Results showed that SO2 fumigation in combination with enriched CO2 atmosphere (14%–17%) could maintain firmness (16.37 N), retard weight loss (10.24%), reduce decay rate (11%), and inhibit the production of ethylene (9.2 μl kg−1 h−1) and malondialdehyde (12.10 μmol/g). Moreover, the treatment consolidated the disease resistance of durian by, first, enhancing peroxidase (POD) and catalase (CAT) activities, and, second, by restraining polyphenol oxidase (PPO) activity, which helped to maintain the cell integrity structures. More importantly, this treatment retained a high sensory score (41.35) and extended the storage life up to 60 days. Therefore, a combination of 1,500 mg/L SO2 fumigation and controlled atmosphere storage (3% O2 + 14%–17% CO2) was the more effective method to delay maturation and senescence and improve the storage quality of durian. Novelty impact statement: Durian (Durio zibethinus Murr.) is susceptible to rapid water loss, softening, browning, and chemical deterioration after harvest, which greatly limits the storage quality and commercial value of fruits. Automatic periodical SO2 fumigation of 1,500 mg/L in conjunction with CO2‐enriched controlled atmosphere storage (3% O2 + 14%–17% CO2) will be a promising postharvest strategy to reduce decay and extend the storage life of fresh durian. [ABSTRACT FROM AUTHOR]

Amplification of androgen receptor (AR) is a common genomic event in metastatic castration-resistant prostate cancer (mCRPC). To evaluate the prognostic value of the amplifications of specific loci in the AR gene in cell-free DNA, we developed a multiplex digital PCR (dPCR) assay that targeted AR enhancer (AR-En), AR exon 1 (AR-E1), AR exon 8 (AR-E8) and OPHN1 (downstream of AR). We selected three relatively stable genes, C2orf16, FAM111B, and GRIA3, as reference controls for copy number normalization. One hundred and eight mCRPC patients were recruited to test the association of specific AR loci amplification with clinical outcome. Using a normalized ratio ≥ 1.92 as cutoff, amplification of AR-En, AR-E1, AR-E8 and OPHN1 was observed in 28, 25, 24 and 19 of 108 mCRPC patients, respectively. Among the 41 patients with AR region amplification, 9 (21.9%) showed amplification at all four selected regions and 15 (36.6%) showed amplification at AR-En, AR-E1, and AR-E8. Six (14.6%) patients showed independent AR-En amplification, while the remaining 3 (7.3%) demonstrated AR-E8 amplification only. Kaplan–Meier analysis showed overall survival's association with the amplification of AR-En (p = 0.02, HR = 1.68 (1.07–2.65)), AR-E8 (p = 0.02, HR = 1.78 (1.08–2.92)) and AR-En-E8 (the combination of AR-En and AR-E8 (p = 0.009, HR = 1.77 (1.15–2.73)). Multivariate models that included AR-En-E8 amplification and clinical factors significantly improved prognostic performance (p = 0.0001). With further validation, the multiplex dPCR assay may assist in prognostication of mCRPC patients. [ABSTRACT FROM AUTHOR]

This research used different 100 kPa O2 pretreatments time (0, 2, 4, and 6 hr) to investigate their effects on qualities of fresh‐cut "Red Fuji" apples during cold storage. Fresh‐cut apples were dipped in acid solution (composed of 1.53% ascorbic acid, 1.10% citric acid, and 0.51% CaCl2) for 15 min and 5 g/L carboxymethylcellulose sodium edible coating (composed of 0.5% CMC, 0.01% Natamycin, and 0.015% Nisin) for 5 min. Then the slices were exposed to 100 kPa O2 for different time before being vacuumed in polyethylene bags. The results showed that pretreatment with 100 kPa O2 inhibited the surface browning, polyphenol oxidase and peroxidase activity and malondialdehyde. Moreover, 100 kPa O2 pretreatment for 4 hr was more effective than other pretreatments time. Intact tissue structure and fewest molds and yeast count during 90 days of storage were also observed in pretreated for 4 hr samples during storage. [ABSTRACT FROM AUTHOR]

• Combined 1-MCP and sterilizing medium is an effective preservation technology. • 1-MCP + O 3 treatment effectively delayed the softening and senescence of fruit. • 1-MCP + O 3 treatment could induce resistance of fruit at earlier shelf storage. • 1-MCP + O 3 could maintain brighter color attributes of peaches during shelf life. • At the end of storage, 1-MCP + O 3 maintained the best integrity of flesh tissue. Physiological senescence and quality deterioration of peach after harvest were the restrict factors of peach shelf quality. As an ethylene inhibitor, 1-Methylcyclopropene (1-MCP) can effectively dealy fruit ripening and senescence, and improve storage quality. However, studies showed that the effect of fruit preservation by only using 1-MCP is unsatisfactory. Therefore, in this study, 1-MCP combined with sterilizing medium including ozone, TiO 2 photocatalytic and epsilon-polylysine (ε-PL) was applied for enhancement of preservative ability with safety and pollution-free. The flow microcirculation was used for enhancing the effect of sterilizing medium. Results showed that all these three treatment methods can enhance the shelf quality of peach fruit. Among them, the combination treatment of 1-MCP and ozone played a more active role in inhibiting decay, respiration, ethylene production, decline of nutrients such as organic acids and soluble solids. Moreover, it maintained bright color value and cell integrity of peach fruit. In addition, the combined treatment of 1-MCP and ozone had significant effects on inducing resistance in fruit and slowing down membrane lipid peroxidation. In conclusion, 1-MCP combined with ozone was an effective method to delay the senescence and improve the storage shelf quality of fruit, which is beneficial to the guidance of production practice and has potential application prospects in fruit preservation. [ABSTRACT FROM AUTHOR]

Molecular analysis of cell-free DNA (cfDNA) that circulates in plasma and other body fluids represents a "liquid biopsy" approach for non-invasive cancer screening or monitoring. The rapid development of sequencing technologies has made cfDNA a promising source to study cancer development and progression. Specific genetic and epigenetic alterations have been found in plasma, serum, and urine cfDNA and could potentially be used as diagnostic or prognostic biomarkers in various cancer types. In this review, we will discuss the molecular characteristics of cancer cfDNA and major bioinformatics approaches involved in the analysis of cfDNA sequencing data for detecting genetic mutation, copy number alteration, methylation change, and nucleosome positioning variation. We highlight specific challenges in sensitivity to detect genetic aberrations and robustness of statistical analysis. Finally, we provide perspectives regarding the standard and continuing development of bioinformatics analysis to move this promising screening tool into clinical practice. [ABSTRACT FROM AUTHOR]

The uneven maturity and severe internal rot of kiwifruit were rapidly accelerated when transferred to room temperature after long‐term controlled atmosphere storage. In this study, the effects of ethrel combined with different flow microcirculation of antiseptic mediums on the shelf‐life quality of "Qinmei" kiwifruit stored at 20°C were evaluated. Results indicated that the combined aerosolization application of 500 mg/L natamycin, 7.5% w/w H2O2 and 0.5 mg/L atomized ozone could control the decay incidence and respiratory rate of ethrel‐treated kiwifruit. Further studies indicated that ethrel and O3 treatment greatly increased the activities of chitinase, β‐1,3‐glucanase, catalase, and superoxide dismutase and produced higher ascorbic acid levels (151.16 mg·100 g−1/FW) to enhance disease‐resistant of kiwifruit. This treatment could inhibit the activity of polyphenol oxidase and delay the process of membrane lipid peroxidation, contributing to preserving the integrity of cell structures well. Moreover, ethrel + O3 treatment could effectively reduce ethylene production (3.12 μl/kg/h) to delay the ripening and senescence of fruit stored at 20°C. More importantly, this treatment exhibited the lowest contents of decay incidence (9.75%), total bacterial count (4.07 log cfu/g), and yeasts and molds (4.18 log cfu/g), and thus extended the shelf life for up to 16 days. Therefore, a combination of ethrel and ozone is a potentially effective method for the maintenance of the shelf‐life properties of kiwifruit after long‐term cold storage. Novelty impact statement: In this study, the treatment of ethrel‐treated with aerosolized ozone of flow microcirculation of 0.5 mg/L O3 could effectively suppress ripening and senescence, enhance antioxidant capacity and disease resistance, reduce the degree of membrane lipid peroxidation, and considerably preserve the integrity of cell structures, which contributed to preventing the penetration of pathogens, retarding the decay incidence, and delaying the shelf‐life quality deterioration of kiwifruit transferred to room temperature after long‐term controlled atmosphere storage. [ABSTRACT FROM AUTHOR]

R5476 --> 484.8 --> Our laboratories study the role of the G9a‐H3K9me2 pathway in PDAC initiation and development in response to oncogenic KRASG12D mutation. Understanding how the epigenomic landscape responds to this mutation remains fundamental for the identification of potential mechanisms and targets for pancreatic oncogenesis. Unfortunately, because of its low levels in human cells and its discrete "block‐like" genome‐wide deposition, the H3K9me2 mark is more difficult to study than more abundant, sharp peak‐forming marks (e.g. H3K27ac). The aim of this study was to perform a comparison among multiple Next Generation Sequencing (NGS) technologies to identify the methodology with the best technical performance for detection of H3K9me2 at a genome‐wide scale. To do so, we performed Chromatin Immunoprecipitation (ChIP), CUT&RUN and CUT&TAG assays for the Histone H3 Lysine 9 di‐methyl histone mark (H3K9me2) followed by NGS on two pancreatic ductal epithelial‐like cells: hTERT‐HPNE E6/E7 and the KRASG12D mutant‐expressing hTERT‐HPNE E6/E7 KRASG12D cells. As expected, ChIP‐Seq required the largest number of total reads for peak detection. Both ChIP‐Seq and CUT&TAG had the highest percentage of high‐quality reads (>75%), while CUT&RUN performed below the 50% mark. No significant differences in library size were observed among all three techniques. Overall, CUT&TAG allowed identification of the largest number of H3K9me2‐marked genes in parental HPNE and KRASG12D‐expressing HPNE cells. Spearman correlation values above 0.8 for inter‐sample comparison indicated a high degree of repeatability for CUT&TAG replicates. In addition, CUT&TAG showed the largest occupation of the H3K9me2 mark near the transcription start site (TSS) of identified genes. Therefore, we have compared three methodologies for the evaluation of H3K9me2 occupation at the genome‐wide scale and identified CUT&TAG as the method with the highest quality, lowest noise‐to‐signal ratio, and highest repeatability. In conclusion, CUT&TAG represents the best option for NGS of the H3K9me2 histone mark in pancreatic cells. Notably, because this methodology is the best among the three tested for miniaturization of epigenomic studies, this information bears relevance to translational research in human, where sample availability is limited. [ABSTRACT FROM AUTHOR]

Background: Chemopreventive agent (CPA) treatment is one of the main preventive options for lung cancer. However, few studies have been done on pharmacodynamic biomarkers of known CPAs for lung cancer. Materials and methods: In this study, we treated mouse models of lung squamous cell carcinoma with three different CPAs (MEK inhibitor: AZD6244, PI-3K inhibitor: XL-147 and glucocorticoid: Budesonide) and examined circulating exosomal miRNAs in the plasma of each mouse before and after treatment. Results: Compared to baselines, we found differentially expressed exosomal miRNAs after AZD6244 treatment (n = 8, FDR < 0.05; n = 55, raw p-values < 0.05), after XL-147 treatment (n = 4, FDR < 0.05; n = 26, raw p-values < 0.05) and after Budesonide treatment (n = 1, FDR < 0.05; n = 36, raw p-values < 0.05). In co-expression analysis, we found that modules of exosomal miRNAs reacted to CPA treatments differently. By variable selection, we identified 11, 9 and nine exosomal miRNAs as predictors for AZD6244, XL-147 and Budesonide treatment, respectively. Integrating all the results, we highlighted 4 miRNAs (mmu-miR-215-5p, mmu-miR-204-5p, mmu-miR-708-3p and mmu-miR-1298-5p) as the key for AZD6244 treatment, mmu-miR-23a-3p as key for XL-147 treatment, and mmu-miR-125a-5p and mmu-miR-16-5p as key for Budesonide treatment. Conclusions: This is the first study to use circulating exosomal miRNAs as pharmacodynamic biomarkers for CPA treatment in lung cancer. [ABSTRACT FROM AUTHOR]

• Biodegradable NTP@PLA film was fabricated by melt processing. • NTP@PLA film exhibited the long-lasting inhibition on Penicillium expansum. • NTP@PLA film displayed biodegradability in soil. • NTP@PLA film displayed a strong control effect on the decay of postharvest grape. Poly (butylene adipate- co -terephthalate) (PBAT)/polylactic acid (PLA) blended with compatibilizers (polycaprolactone, PCL; poly (ethylene glycol), PEG; titanium dioxide, nano-TiO 2) (TP@PLA composites) were developed by melt processing. Natamycin incorporated into TP@PLA blend composites formed NTP@PLA films, which exhibited high tensile strength (24.1–43.5 MPa) and elongation at break (85.8–258.2 %), and exhibited good oxygen permeability, water vapor permeability, surface hydrophobicity and biodegradability. The in vitro results revealed that inhibition of Penicillium expansum cell growth of the NTP@PLA films with addition of 1.0 wt% natamycin reached 95.72 %. The NTP@PLA film with natamycin effectively reduced incidence of decay (1.52 %) on grapes, maintained their quality, and inhibited the growth of pathogenic fungi to up to 0.42 log cfu·g−1. This study generates new insights into the preservation properties of antimicrobial NTP@PLA film, which endow it with great application potential as a novel and eco-friendly packaging material for the food industry. [ABSTRACT FROM AUTHOR]

Objectives Cell free tumor DNA (cfDNA) circulating in blood has a great potential as biomarker for cancer clinical management. The objective of this study is to evaluate if cfDNA in blood plasma is detectable in early stage lung cancer patients. Materials and methods We extracted cfDNAs and tumor tissue DNAs from 8 lung adenocarcinoma patients. We also extracted cfDNAs from 8 normal controls. To evaluate copy number variations (CNV) and identify potential mutations, we performed low pass whole genome sequencing and targeted sequencing of 50 cancer genes. To accurately reflect the tumor-associated genomic abnormality burden in plasma, we developed a new scoring algorithm, plasma genomic abnormality (PGA) score, by summarizing absolute log2 ratios in most variable genomic regions. We performed digital PCR and allele-specific PCR to validate mutations detected by targeted sequencing. Results and conclusions The median yield of cfDNA in 400ul plasma was 4.9ng (range 2.25–26.98 ng) in patients and 2.32 ng (range 1.30–2.81 ng) in controls ( p = 0.003). The whole genome sequencing generated approximately 20 million mappable sequence reads per subject and 5303 read counts per 1 Mb genomic region. Log2 ratio-based CNV analysis showed significant chromosomal abnormality in cancer tissue DNAs and subtle but detectable differences in cfDNAs between patients and controls. Genomic abnormality analysis showed that median PGA score was 9.28 (7.38–11.08) in the 8 controls and 19.50 (5.89–64.47) in the 8 patients ( p = 0.01). Targeted deep sequencing in tumor tissues derived from the 8 patients identified 14 mutations in 12 different genes. The PCR-based assay confirmed 3 of 6 selected mutations in cfDNAs. These results demonstrated that the PGA score and cfDNA mutational analysis could be useful tool for the early detection of lung cancer. These blood-based genomic and genetic assays are noninvasive and may sensitively distinguish early stage disease when combined with other existing screening strategies including low-dose CT scanning. [ABSTRACT FROM AUTHOR]

Background Extracellular microRNAs (miRNAs) embedded in circulating exosomes may serves as prognostic biomarkers in cancer. Objective To identify and evaluate plasma exosomal miRNAs for prognosis in castration-resistant prostate cancer (CRPC). Design, setting, and participants RNA sequencing was performed to identify candidate exosomal miRNAs associated with overall survival in a screening cohort of 23 CRPC patients. Candidate miRNAs were further evaluated for prognosis using quantitative real-time polymerase chain reaction in a follow-up cohort of 100 CRPC patients. Outcome measurements and statistical analysis Cox regression and Kaplan-Meier survival analyses were used to evaluate survival association using candidate miRNAs along with clinical prognostic factors. Results and limitations RNA sequencing in screening cohort generated approximately 6.80 million mappable reads per patient. Of those with normalized read counts ≥5, 43% were mapped to miRNAs for a total of 375 known and 57 novel miRNAs. Cox regression analysis identified an association of miR-1290, -1246, and -375 with overall survival (false discover rate < 0.05). Of those, higher levels of miR-1290 and -375 were significantly associated with poor overall survival ( p < 0.004) in the follow-up cohort. Incorporation of miR-1290/-375 into putative clinical prognostic factors-based models in CRPC stage significantly improved predictive performance with a time-dependent area under the curve increase from 0.66 to 0.73 ( p = 6.57 × 10 −6 ). Conclusions Plasma exosomal miR-1290 and miR-375 are promising prognostic biomarkers for CRPC patients. Prospective validation is needed for further evaluation of these candidate miRNAs. Patient summary In this study, we evaluated whether small RNAs circulating in blood could be used to predict clinical outcomes in late-stage prostate cancer patients. We identified two blood-based small RNAs whose levels showed significant association with survival. Our results warrant further investigation because the noninvasive blood-based test has great potential in the management of late-stage prostate cancer. [ABSTRACT FROM AUTHOR]

• In-package aerosolization technology associated with antimicrobials system was designed. • Aerosolized ɛ-PL and ClO 2 could inhibit postharvest black mold caused by aspergillus niger (A. niger) on apple fruit. • Aerosolized antimicrobials increased corresponding defense-related enzyme activity of apples. • Aerosolized antimicrobials produced higher phenolic levels of apples. • Aerosolized antimicrobials improved apple's shelf life and quality. The present study aimed to investigate the inhibition of in-package aerosolized aqueous antimicrobials against postharvest black mold caused by Aspergillus niger (A. niger) on apple fruit and in maintaining fruit quality. Apple fruit is susceptible to A. niger infection during storage, resulting in a significant decline in its quality. In this paper, the ability of chlorine dioxide (ClO 2), Epsilon-polylysine (ɛ-PL), hydrogen peroxide (H 2 O 2) and ozone (O 3) to prevent and control Aspergillus infection in postharvest apples was evaluated. Results indicated that the treatments of 400 mg L−1ClO 2 , 500 mg L−1 and 1000 mg L−1 ɛ-PL could effectively alleviate the severity of postharvest black mold (A. niger) of apples and inhibit mycelial growth of A. niger. In addition, 0.5 mg L−1 O 3 and 5% H 2 O 2 also inhibited the mycelial growth of A. niger in treated apples. Further studies indicated that aerosolized ClO 2 and ε-PL increased corresponding defense-related enzyme activity and produced higher phenolic levels to improve disease-resistant of apples. Moreover, aerosolized ClO 2 , ε-PL, H 2 O 2 and O 3 could be effective for maintaining quality of apple fruit during 24 days of storage at 20 °C. The present study gives a first insight into the A. niger control effect of in-package aerosolization technology associated with antimicrobials, which may be a potential method for the inhibition of A. niger on apple fruit. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, tannic acid (TA), a natural antioxidant, is successfully encapsulated into a plant‐based guar gum fibrous mat by electrospinning without using an organic solvent. An upper threshold of 10 wt% TA (based on the dry weight of guar gum [GG]) and 2 wt% guar gum is the optimum composition to achieve a defect‐free structure through electrospinning. The obtained nanofibers have a mean diameter of 96 ± 22 nm. The effect of the encapsulated TA in the fibrous mat (200 ppm) on the oxidation of unrefined flaxseed oil (FO) is investigated over 30 days of storage at an elevated temperature (60 °C) and compared with the effect of butylated hydroxytoluene (BHT), a synthetic antioxidant, and non‐encapsulated TA at the same concentrations. Changes in the fatty acid composition, the conjugated diene content, the peroxide value, the content of thiobarbituric acid reactive substances (TBARS) and the p‐anisidine content are monitored as indicators of the oxidative stability. The TA fibrous mat exhibits different inhibitory effects on the oxidation of unsaturated fatty acids and is more effective than non‐encapsulated TA and BHT in reducing the rate of primary oxidation and secondary oxidation of FO as evaluated by all the oxidation indicators except the TBARS values for which BHT displays the greatest inhibition. Overall, the results demonstrate that the encapsulation of natural antioxidants into fibrous mats could potentially be used to preserve edible oils. Practical Applications: This is the first paper using plant‐based fibrous mats encapsulating natural antioxidant to improve the oxidative of flaxseed oil (FO) during storage. Compared with macro Tannic acid (TA), encapsulating TA in nano‐scale delivery system is more effective in delaying both the primary and secondary oxidation reactions of FO throughout the entire storage time. The results demonstrate that encapsulation of TA in fibrous mat could be potentially used to preserve oil. The formation of this nanofiber mat in this system is manufactured without using any synthetic chemicals. The plant‐derived components (GG and TA) are both recognized as safe by FDA and even edible. It can be directly added to crude oil systems during oilseed refining processing or used as coating material to fix on the surface of existing packaging bottle in order to prevent edible oil from oxidation, which would be beneficial in oil preservation and other related fields. This is the first paper using plant‐based nanoscale delivery system encapsulating natural antioxidant to improve the oxidative of flaxseed oil during storage. The plant‐derived components (guar gum and tannic acid) are both recognized as safe by FDA and even edible. The simple preparation process, effectiveness, and food‐grade functionality provide a novel alternative to synthetic antioxidants to protect edible oil from oxidation. [ABSTRACT FROM AUTHOR]