GC/MS-based untargeted metabolomics reveals the differential metabolites for discriminating vintage of Chenxiang-type baijiu.

The "outstanding and unique aged aroma" of Chinese Chenxiang-type baijiu (CXB)-Daoguang 25 (DG25) mainly originates from a "extraordinary storage technology" of Mujiuhai (a wooden container), so it is mysterious and interesting. In this study, an untargeted GC/MS-based metabolomics was used to reveals the volatile differential metabolites for discriminating six different vintages of DG25 combing with chemometrics. A total of 100 volatile metabolites (including unknowns) were extracted and identified, including esters (41%), alcohols (10%) and acids (7%) so on. Finally, 33 differential metabolites were identified as aging-markers. Among them, 25 aging-markers showed a downtrend, including 17 esters such as ethyl acetate, ethyl hexanoate and ethyl palmitate so on. Moreover, it was interesting and to further study that furans showed a significant downtrend. Statistically speaking, ethyl benzoate played an important role in discriminating vintage of 1Y and 3Y, and the other 24 differential metabolites with downtrend discriminating the unstored (0Y-aged) DG25. Eight differential metabolites, such as ethyl octanoate, benzaldehyde, 3-methylbutanol and 1,1-diethoxyaccetal so on increased during aging of DG25, and they played a statistical role in discriminating the 5Y-, 10Y- and 20Y-aged DG25. This study provides a theoretical basis way for the formation mechanism of aging aroma for CXB.

Comparative study the alleviated effects of various oligosaccharides on colitis in mice.

Oligosaccharides, namely, chitosan oligosaccharides (COS), fructooligosaccharides (FOS), and 2'-fucosyllactose (2-FL) were used to prevent the dextran sulfate sodium (DSS)-induced colitis in vivo based on antioxidant properties and anti-inflammatory activities, further comparing their alleviating effects to investigate the optimal anti-inflammatory agent. The results showed COS demonstrated the highest antioxidant properties, with a DPPH scavenging rate of 37.4% and an ABTS scavenging rate of 46.4% in these oligosaccharides. Consequently, COS exhibited the best anti-inflammatory activities on inflamed RAW 264.7 cells. Furthermore, the COS intervention demonstrated the best attenuated effects on decrease in the body weight and increase in DAI score, as well as on the overexpressed inflammatory factors and underexpressed short-chain fatty acids (SCFAs) compare to FOS and 2-FL. Therefore, these beneficial changes help prevent the damage to the inflammatory lesions in colonic histopathology. Additionally, COS significantly increased the diversity of gut microbiota and the ratio of Firmicutes/Bacteroidetes at phylum level. It also up-regulated the abundance of Lactobacillaceae and down-regulated Helicobacteraceae and Desulfovibrionaceae more effectively at family level to maintain oral tolerance against DSS. In short, COS intervention could be a promising nutritional strategy for alleviating colitis.

Performance analysis and structural characterization of flaxseed gum/chitosan/cinnamaldehyde composite films.

The low mechanical strength, water deficiency, and oxidative protection of organic membranes impede their use as food-grade packaging materials. Cinnamaldehyde (CIN) tends to lose its activity owing to its instability. In this study, CIN was added to flaxseed gum (FG)/chitosan (CS) films prepared in a "sandwich" structure. The influence of CIN dosage on the properties of the composite films was studied, and the film formation mechanism of the membrane was explored. The elongation at break, water vapor permeability, oxygen permeability, and light transmittance of the composite film with 1.5% CIN were lower than those of the FG/CS/FG film. Supplementation of the composite membrane with CIN generated new hydrogen bonds, electrostatic interactions, and C-O-C bonds, which converted the structure of the composite film into a sheet and increased its crystallinity without markedly affecting its thermal stability. Therefore, CIN is an extremely useful additive for improving the applicability of flaxseed gum/CS membranes as food-grade packaging films.

Effects of Ultrasound-Assisted Extraction on Structure and Rheological Properties of Flaxseed Gum.

In this study, flaxseed gum (FG) was extracted using hot water extraction and ultrasonic-assisted extraction. The yield, molecular weight distribution, monosaccharide composition, structure, and rheological properties of FG were analyzed. The FG yield (9.18) achieved using ultrasound-assisted extraction (this sample was labeled as UAE) was higher than the yield (7.16) achieved with hot water extraction (this sample was labeled as HWE). The polydispersity, monosaccharide composition, and characteristic absorption peaks of the UAE were similar to that of the HWE. However, the UAE had a lower molecular weight and looser structure than the HWE. Moreover, zeta potential measurements indicated that the UAE exhibited better stability. An analysis of the rheological properties showed that the viscosity of the UAE was lower. Thus, the UAE had an effectively better yield of FG, preliminarily modified structure, and rheological properties, and provided a theoretical basis for its application in food processing.

Metabolomic fingerprinting based on network analysis of volatile aroma compounds during the forced aging of Huangjiu: Effects of dissolved oxygen and temperature.

Introduction: Huangjiu is an important Chinese alcoholic beverage, usually prepared from rice. Although its unique flavor improves with prolonged storage in traditional pottery jars, knowledge of the aging mechanism, necessary for commercialization of an optimum product, remains unclear. Methods: Here, volatile aroma compounds from forced aged samples exposed to different temperatures and oxygen treatments were measured by GC/MS. After retention time alignment and normalization, the peak vectors were compared over storage time using Pearson's correlation, and a correlation network was established. Marker compounds, representative of traditionally aged Huangjiu, were then monitored and compared to similar compounds in the forced aged product. Results and discussion: Correlation network analysis revealed the following: Temperature had little effect on most aroma compounds; alcohols, acids, and esters all increased with increasing dissolved oxygen, while polyphenols, lactones, and ketones were readily oxidized; aldehydes (e.g., furfural and benzaldehyde) were highly dependent on both temperature and dissolved oxygen. Dynamic changes in the targeted aging-markers showed that a higher initial oxygen concentration intensified the "aging-aroma" of Huangjiu in the early and middle stages of storage. Consequently, careful control of oxygen supplementation and storage temperature could be beneficial in controlling the desirable flavor of Huangjiu in the artificially aged product.

The relationship between serum lipid levels and colorectal serrated lesions: A systematic review and meta-analysis.

Objective: To clarify the relationship between colorectal serrated lesions and serum lipid levels, and provide a scientific basis for the identification and early clinical prevention and treatment of populations that are at risk for colorectal serrated lesions. Methods: Studies comparing serum lipid levels in patients with colorectal serrated lesions and controls were searched in PubMed, Embase, Web of Science, the Cochrane Library, China Biomedical Literature Database, CNKI, Wanfang Database, and VIP Database. Relevant literature was screened according to the inclusion and exclusion criteria. The mean and standard deviation of the serum lipid levels in patients and controls were extracted from the included literature. The combined weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated using Review Manager 5.0 software to evaluate the relationship between serum lipid levels and colorectal serrated lesions. Publication bias of the included studies was evaluated by the Egger test. Results: Twenty-three studies were included, comprising 2,063 patients and 63,909 controls. The serum high-density lipoprotein cholesterol (HDL-C) levels in the case group was significantly lower than in the control group (WMD = -0.122 mmol/L, 95% CI: 0.170-0.073). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and serum triglyceride levels in the case group were significantly higher than in the control group, and the WMDs were 0.180 mmol/L (95% CI: 0.061-0.299), 0.155 mmol/L (95% CI: 0.038-0.273), and 0.241 mmol/L (95% CI: 0.181-0.302), respectively. Conclusion: Colorectal serrated lesions may be related to blood lipid levels. Hyperlipidemia might be a risk factor for colorectal serrated lesions.

Cell-cycle and apoptosis related and proteomics-based signaling pathways of human hepatoma Huh-7 cells treated by three currently used multi-RTK inhibitors.

Sorafenib, lenvatinib and regorafenib, the multi-RTK inhibitors with potent anti-angiogenesis effects, are currently therapeutic drugs generally recommended for the patients with advanced hepatocellular carcinoma (HCC). To date, however, there have been no published studies on the mechanism underling differential effects of the three drugs on HCC cell proliferation, and the proteomic analysis in HCC cell lines treated by regorafenib or lenvatinib. The present study for the first time performed a direct comparison of the cell cycle arrest and apoptosis induction in the Huh-7 cells caused by sorafenib, regorafenib and lenvatinib at respective IC50 using flow cytometry technique, as well as their pharmacological interventions for influencing whole cell proteomics using tandem mass tag-based peptide-labeling coupled with the nLC-HRMS technique. Sorafenib, regorafenib and lenvatinib at respective IC50 drove the remaining surviving Huh-7 cells into a G0/G1 arrest, but lenvatinib and regorafenib were much more effective than sorafenib. Lenvatinib produced a much stronger induction of Huh-7 cells into early apoptosis than sorafenib and regorafenib, while necrotic cell proportion induced by regorafenib was 2.4 times as large as that by lenvatinib. The proteomic study revealed 419 proteins downregulated commonly by the three drugs at respective IC50. KEGG pathway analysis of the downregulated proteins indicated the ranking of top six signaling pathways including the spliceosome, DNA replication, cell cycle, mRNA surveillance, P53 and nucleotide excision repair involved in 33 proteins, all of which were directly related to their pharmacological effects on cell cycle and cell apoptosis. Notably, lenvatinib and regorafenib downregulated the proteins of PCNA, Cyclin B1, BCL-xL, TSP1, BUD31, SF3A1 and Mad2 much more strongly than sorafenib. Moreover, most of the proteins in the P53 signaling pathway were downregulated with lenvatinib and regorafenib by more than 36% at least. In conclusion, lenvatinib and regorafenib have much stronger potency against Huh-7 cell proliferation than sorafenib because of their more potent effects on cell cycle arrest and apoptosis induction. The underling mechanism may be at least due to the 33 downregulated proteins centralizing the signal pathways of cell cycle, p53 and DNA synthesis based on the present proteomics study.

Variations in the structural and functional properties of flaxseed gum from six different flaxseed cultivars.

Although flaxseed gum (FG) has been widely studied, the differences in its structure and function with respect to various flaxseed cultivars remain unclear. In this study, our objective was to examine the differences between FG samples obtained from different flaxseed cultivars based on their structural and functional properties. Specifically, FG samples from the different cultivars were extracted via hot water extraction followed by ethanol precipitation. Thereafter, they were analyzed via zeta potential measurements, Fourier-transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), and scanning electron microscopy (SEM). The results demonstrated that the different cultivars showed significantly different FG yields (p < .05; range, 5.83%-7.36%). Further, the FTIR spectra of the FG samples were slightly different but showed typical polysaccharide absorption peaks. Furthermore, the XRD patterns obtained predominantly showed an amorphous region and a small crystalline region, while the SEM images obtained at 1,000× magnification revealed that the samples had smooth and irregular surfaces, with a scaly structure. However, at 20,000× magnification, the FG samples showed slight structural differences. Additionally, the zeta potentials of the FG samples (range, -19.4 to -30.6 mV; p < .05) were cultivar-dependent and indicated the presence of negatively charged macromolecules. This implies that the FG samples from the different cultivars show diverse structural properties. Our findings not only provide useful information regarding FG samples extracted from different cultivars but also serve as a theoretical basis for the application of FG in food processing.

Genome-wide analysis of gibberellin-dioxygenases gene family and their responses to GA applications in maize.

Gibberellin-dioxygenases genes plays important roles in the regulating plant development. However, Gibberellin-dioxygenases genes are rarely reported in maize, especially response to gibberellin (GA). In present study, 27 Gibberellin-dioxygenases genes were identified in the maize and they were classified into seven subfamilies (I-VII) based on phylogenetic analysis. This result was also further confirmed by their gene structure and conserved motif characteristics. And gibberellin-dioxygenases genes only occurred segmental duplication that occurs most frequently in plants. Furthermore, the gibberellin-dioxygenases genes showed different tissue expression pattern in different tissues and most of the gibberellin-dioxygenases genes showed tissue specific expression. Moreover, almost all the gibberellin-dioxygenases genes were significantly elevated in response to GA except for ZmGA2ox2 and ZmGA20ox10 of 15 gibberellin-dioxygenases genes normally expressed in leaves while 10 and 11 gibberellin-dioxygenases genes showed up and down regulated under GA treatment than that under normal condition in leaf sheath. In addition, we found that ZmGA2ox1, ZmGA2ox4, ZmGA20ox7, ZmGA3ox1 and ZmGA3ox3 might be potential genes for regulating balance of GAs which play essential roles in plant development. These findings will increase our understanding of Gibberellin-dioxygenases gene family in response to GA and will provide a solid base for further functional characterization of Gibberellin-dioxygenases genes in maize.

Maize Ethylene Response Factor ZmERF061 Is Required for Resistance to Exserohilum turcicum.

Plants have evolved a series of sophisticated defense mechanisms to help them from harm. Ethylene Response Factor (ERF) plays pivotal roles in plant immune reactions, however, its underlying mechanism in maize with a defensive function to Exserohilum turcicum (E. turcicum) remains poorly understood. Here, we isolated and characterized a novel ERF transcription factor, designated ZmERF061, from maize. Phylogenetic analysis revealed that ZmERF061 is a member of B3 group in the ERF family. qRT-PCR assays showed that the expression of ZmERF061 is significantly induced by E. turcicum inoculation and hormone treatments with salicylic acid (SA) and methyl jasmonate (MeJA). ZmERF061 was proved to function as a nucleus-localized transcription activator and specifically bind to the GCC-box element. zmerf061 mutant lines resulted in enhanced susceptibility to E. turcicum via decreasing the expression of ZmPR10.1 and ZmPR10.2 and the activity of antioxidant defense system. zmerf061 mutant lines increased the expression of the SA signaling-related gene ZmPR1a and decreased the expression of the jasmonic acid (JA) signaling-related gene ZmLox1 after infection with E. turcicum. In addition, ZmERF061 could interact with ZmMPK6-1. These results suggested that ZmERF061 plays an important role in response to E. turcicum and may be useful in genetic engineering breeding.

Age plays an important role in the decision of definitive concurrent chemoradiotherapy (CCRT) for esophageal squamous cell carcinoma (ESCC): a propensity-score matched analysis of multicenter data (3JECROG R-02A).

BACKGROUND: To examine the survival benefit of definitive concurrent chemoradiotherapy (CCRT) compared to radiotherapy alone in patients with esophageal squamous cell carcinoma (ESCC) using a real-world patient population. METHODS: This retrospective study included 2,762 patients with ESCC across ten medical centers in China from 2001 to 2017. A total of 1,133 patients received radiotherapy alone and 815 patients were treated with CCRT. The patient survival rates were assessed by propensity-score matching (PSM) and subgroup analysis. RESULTS: The baseline characteristics were significantly different between the two groups, with the CCRT group showing a higher proportion of males, younger patients, cervical/upper thoracic cancers, and worse T and N stages. There were no significant differences in the clinical characteristics between the two groups after PSM. Before PSM, the median overall survival (OS) rates were 31.2 and 24.1 months in the CCRT and RT alone groups, respectively, demonstrating the superior therapeutic effects (TEs) of the CCRT. However, the median OS rates were not significantly different between the two groups after PSM (32.6 and 39.4 months in the CCRT and radiotherapy alone groups, respectively). The subgroup analyses revealed that the median OS was significantly better in the CCRT group compared to the radiotherapy alone group (37.5 vs. 25.1 months, respectively) in patients less than 70 years of age [hazard ratio (HR) 0.782, 95% confidence interval (CI): 0.657 to 0.932]. In contrast, in patients 70 years of age and older, the 5-year survival rate was poorer in the CCRT group (34.8%) compared to the radiotherapy alone group (73.4%). Therefore, CCRT was an independent poor prognostic risk factor (HR 3.206, 95% CI: 2.168 to 4.740). CONCLUSIONS: CCRT may not be suitable for all patients with localized ESCC. Younger patients less than 70 years of age might benefit significantly from CCRT. However, in patients aged 70 years and older, the potential survival benefit of CCRT and the optimal combination treatment regimens require further investigation.

A Novel ERF Transcription Factor, ZmERF105, Positively Regulates Maize Resistance to Exserohilum turcicum.

The ethylene response factor (ERF) plays a crucial role in plant innate immunity. However, the molecular function of ERF in response to Exserohilum turcicum (E. turcicum) remains unknown in maize. In this study, a novel ERF gene, designated as ZmERF105, was firstly isolated and characterized. The ZmERF105 protein contains an APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) domain and a conserved LSPLSPHP motif in its C-terminal region. ZmERF105 protein was exclusively localized to the nucleus. ZmERF105 expression responded to E. turcicum treatment. Yeast one-hybrid and transcription activity assays revealed that ZmERF105 is an activator of transcription and binds to GCC-box elements. Over-expression of ZmERF105 was shown to increase maize resistance against E. turcicum, and erf105 mutant lines displayed opposite phenotype. Moreover, the activities of superoxide dismutase (SOD) and peroxidase (POD) in the ZmERF105 over-expression lines were markedly higher than in the wild-type maize lines (WT) after infection with E. turcicum, and were compromised in the erf105 mutant lines. Simultaneously, ZmERF105 over-expression lines enhanced the expression of several pathogenesis-related (PR) genes, including ZmPR1a, ZmPR2, ZmPR5, ZmPR10.1, and ZmPR10.2 after infection with E. turcicum. In contrast, the expression of PR genes was reduced in erf105 mutant lines. Our work reveals that ZmERF105 as a novel player of the ERF network and positively regulates the maize resistance response to E. turcicum.

Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma.

BACKGROUND: Chemo-resistance in hepatocellular carcinoma (HCC) is a major problem, and acquired drug resistance prevents cancer therapies from achieving complete responses. Molecular targeting therapy presents an opportunity to impede tumor through combination or sequential therapy, while the accurate effect is vague. METHODS: The efficacy of combinations between oxaliplatin and anti-cancer molecular targeting drugs was screened. Strangely, the combined chemotherapy with oxaliplatin and saracatinib induced significantly antagonistic effects. Then the antitumor effects of combined treatment with saracatinib and oxaliplatin were confirmed in wide type HCC as well as in saracatinib- and oxaliplatin-resistant HCC. RNA sequencing was used to explore the resistance mechanism, and the roles of ATP-binding cassette transporter G1 (ABCG1) and Wnt signaling in oxaliplatin resistance were confirmed. RESULTS: Chemotherapy with oxaliplatin and saracatinib individually induced strong anti-HCC effects, while combined or sequential treatment of HCC cells with these two drugs exhibited reduced efficacy compared to treatment with the single drugs. And it was saracatinib treatment caused oxaliplatin resistance. RNA sequencing revealed 458 genes that were altered by treatment with saracatinib and oxaliplatin. Of these, the gene encoding ABCG1 and Wnt-associated genes were significantly upregulated. Upregulation of ABCG1 and oxaliplatin resistance were associated with activation of Wnt signaling. Interference with ABCG1 expression or inhibition of Wnt signaling resulted in reversal of the saracatinib-induced oxaliplatin resistance in HCC. CONCLUSIONS: These studies demonstrated that combined or sequential chemotherapy with oxaliplatin and saracatinib reduced antitumor efficacy, and this antagonism was attributed to the activation of Wnt signaling and upregulation of ABCG1 by saracatinib.

Retrospective analysis of safety profile of high-dose concurrent chemoradiotherapy for patients with oesophageal squamous cell carcinoma.

BACKGROUND AND PURPOSE: To evaluate the safety profile and efficacy of high-dose (60 Gy) concurrent chemoradiotherapy (CCRT) compared with standard-dose (50.4-54 Gy) CCRT. MATERIALS AND METHODS: Patients with oesophageal squamous cell carcinoma (OSCC) undergoing CCRT were eligible for a propensity score matched cohort (1:1 for high dose versus standard dose). Adverse events, local control (LC) and overall survival (OS) were assessed. RESULTS: A total of 380 patients with good balance in observed co-variables were enrolled. OS and LC rates of patients receiving high-dose CCRT were significantly higher than those receiving standard-dose CCRT, with the 10-year OS at 24% versus 13.3%, respectively. In contrast, there was a trend towards increased grades 2-3 acute oesophagitis toxicity among patients receiving high-dose versus standard-dose CCRT (37.4% versus 27.9%, respectively). None experienced grade 5 acute oesophagitis and grade 4 acute toxicities were rare. Similar rates of late radiation oesophagitis, radiation pneumonitis, gastrointestinal reactions and haematological toxicities were observed between patients receiving high-dose versus standard-dose CCRT. Six patients (3.2%) receiving high-dose CCRT experienced >grade 3 leucocytopaenia, and two (1.1%) received standard-dose CCRT, whereas none experienced >grade 3 thrombocytopaenia or anaemia. Three patients (2.3%) receiving high-dose CCRT died of infections caused by myelosuppression. Multivariate analysis showed that anaemia is a significant independent predictor of poor prognosis. CONCLUSIONS: Compared with standard-dose CCRT, high-dose CCRT yielded more favourable local control and survival outcomes for patients with OSCC. Grades 2-3 acute oesophagitis toxicity in patients undergoing high-dose CCRT increased, whereas severe, life-threatening toxicities (>grade 3) did not.

Biomechanical study of three kinds of internal fixation for the treatment of sacroiliac joint disruption using biomechanical test and finite element analysis.

BACKGROUND: To compare the stability of sacroiliac joint disruption fixed with three kinds of internal fixation using both biomechanical test and finite element analysis. METHODS: Five embalmed specimens of an adult were used. The symphysis pubis rupture and left sacroiliac joint disruption were created. The symphysis pubis was stabilized with a five-hole plate. The sacroiliac joint disruption was fixed with three kinds of internal fixation in a randomized design. Displacements of the whole specimen and shifts in the gap were recorded. Three-dimensional finite element models of the pelvis, the pelvis with symphysis pubis rupture and left sacroiliac joint disruption, and three kinds of internal fixation techniques were created and analyzed. RESULTS: Under the vertical load, the displacements and shifts in the gap of the pelvis fixed with minimally invasive adjustable plate (MIAP) combined with one iliosacral (IS) screw were the smallest, and the average displacements of the pelvis fixed with an anterior plate were the largest one. The differences among them were significant. In finite element analysis and MIAP combined with one IS screw fixation showed relatively best fixation stability and lowest risks of implant failure than two IS screws fixation and anterior plate fixation. CONCLUSION: The stability of sacroiliac joint disruption fixed with MIAP combined with one IS screw is better than that fixed with two IS screws and anterior plate under vertical load.

Target-guided screening of fragments (TGSOF) in the discovery of inhibitors against EV-A71 3C protease.

Target-guided screening of fragments (TGSOF) was developed and employed in the identification of EV-A71 3C protease (3Cpro) inhibitors. We identified 4-acetylpyridine and 3-acetylpyridine as effective P3 fragments of an inhibitor and obtained the corresponding irreversible inhibitors 12c and 12fvia this method. Furthermore, based on 12c and 12f, we have obtained reversible inhibitors 17c and 17f. These results demonstrated that TGSOF is a useful strategy for identifying suitable fragments in developing leads in drug discovery.

The diffusion-weighted magnetic resonance imaging (DWI) predicts the early response of esophageal squamous cell carcinoma to concurrent chemoradiotherapy.

PURPOSE: To investigate the predictive value of serial diffusion-weighted MRI (DWI) on tumor response of the concurrent chemoradiotherapy (CCRT) for esophageal squamous cell carcinoma (ESCC) and to determine the optimal time point of DWI measurements. METHODS AND MATERIALS: From June 2010 to October 2011, 38 ESCC patients were consecutively enrolled into this prospective cohort study. During their treatment, the longitudinal DWIs were acquired at beginning and every week during the course of CCRT. ADC maps were generated from there DWIs. The tumor responses were evaluated according to the RECIST. RESULTS: (1) At completion of CCRT, 20 (52.6%) and 18 (47.4%) patients were evaluated as CR and PR, respectively. Over the time points of measures, the series of ADC values (10-3mm2/s) in whole GTV were consistently characterized with higher (all p<0.05) for these CR patients as their means (std) were 2.24 (0.49), 2.23 (0.51), 2.44 (0.57), 2.54 (0.52), 2.70 (0.46), 2.80 (0.55), 2.92 (0.62), compared with these PR patients as 1.83 (0.31), 1.79 (0.21), 1.87 (0.30), 1.97 (0.37), 2.15 (0.44), 2.26 (0.46), 2.32 (0.51), respectively. However, the ADC change rates (ΔADC) of two groups were found to be similar. These results were also supported by the multivariate ANOVA analyses. The same analysis results of DWI based GTV volumes were also found. (2) The comparisons of logistic regression analysis indicated that only the ADC values at Week 3 (15 fractions) were an independent prognostic factor of tumor response (OR=0.303, p=0.003). ROC curve analysis showed that Area Under Curve for ADC values of the end of 2nd and 3rd weeks were biggest (0.822) and the prediction efficacy was comparatively optimized. The corresponding cut-off values were 2.11 and 2.14 (10-3mm2/s), respectively. (3) Additional analyses on those eight patients with tumor local recurrence within 1year demonstrated the level-off after the continuously increased ADC values till Week 4. CONCLUSIONS: DWI can be used as a biomarker to predict TE of esophageal cancers in early time during CCRT. The treatment-induced change in ADC of whole GTV during the first 2-3weeks can be highly predictive to TE. The unchanged ADC value in late period may indicate the high tendency of tumor recurrence after 1year.

Structure-activity relationship study of peptidomimetic aldehydes as enterovirus 71 3C protease inhibitors.

A series of peptidomimetic aldehydes were designed, synthesized, and evaluated for their biochemical activity against 3C protease (3Cpro) and anti-enterovirus 71 (EV71) activity in vitro. Molecular docking revealed that 5s (IC50 = 0.22 ± 0.07 µM, EC50 = 0.18 ± 0.05 µM) could bind well to the active site of EV71 3Cpro, which was consistent with the biological data compared to reference 5a (IC50 = 0.54 ± 0.02 µM, EC50 = 0.26 ± 0.07 µM). Structure and relationship study led to the discovery of aldehyde 5x (IC50 = 0.10 ± 0.02 µM, EC50 = 0.11 ± 0.07 µM), which exhibited the most potent 3Cpro inhibitory and antiviral activity.

A 3,7-Dihydroxyphenoxazine-based Fluorescent Probe for Selective Detection of Intracellular Hydrogen Peroxide.

A novel N-borylbenzyloxycarbonyl-3,7-dihydroxyphenoxazine fluorescent probe (NBCD) for detecting H2O2 in living cells is described. The probe could achieve high selectivity for detecting H2O2 over other biological reactive oxygen species (ROS). In addition, upon addition of H2O2, NBCD exhibited color change from colorless to pink, which makes it a "naked-eye" probe for H2O2 detection. NBCD could not only be used to detect enzymatically generated H2O2 but also to detect H2O2 in living systems by using fluorescence spectroscopy, with a detection limit of 2 µm. Importantly, NBCD enabled the visualization of epidermal growth factor (EGF)-stimulated H2O2 generation inside the cells.

Relaxant and contractile responses of detrusor muscle strips obtained from bladder outlet-obstructed rats treated with doxazosin enantiomers.

(-)Doxazosin, one of (±)doxazosin enantiomers, was speculated to have a pharmacological enantioselectivity between the cardiovascular system and the urinary system by comparison with (+)doxazosin. Therefore, to evaluate the potential benefits of (-)doxazosin in the treatment of benign prostate hyperplasia, we compared the effects of the 3 agents, using rat mesenteric artery preparations and obstructed bladder strips. Concentration-response curves for carbachol (contractile response) and isoprenaline (relaxant response) in detrusor muscle strips of the bladder outlet obstruction (BOO) rats were shifted to the left, with significant increases in the Emax values, and significant decreases in the EC50 values by comparison with the sham-operated rats (P < 0.05, n = 10). The enhanced responses in detrusor muscle strips of the BOO rats treated with (±)doxazosin and its enantiomers at 3 mg·(kg body mass)(-1)·day(-1) for 2 weeks returned to normal levels, and the 3 agents inhibited the enhanced responses to carbachol and isoprenaline to the same extent. On the other hand, the 3 agents uncompetitively inhibited the vasoconstrictive response curves for NA in the rat isolated mesenteric artery, and the pKB value of (-)doxazosin at vascular α1-adrenoceptors was significantly smaller (P < 0.05, n = 6) than that of (+)doxazosin or (±)doxazosin. In conclusion, although (-)doxazosin inhibits vascular functional α1-adrenoceptors more weakly than (+)doxazosin, both agents equally ameliorate the enhanced responses in detrusor muscle of BOO rats, suggesting that the chiral carbon atom in the molecular structure of doxazosin does not affect its beneficial effects in the bladder smooth muscle of BOO rats.