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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]

• 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]

• 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]

• 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]