Redox proteomics of PANC-1 cells reveals the significance of HIF-1 signaling protein oxidation in pancreatic ductal adenocarcinoma pathogenesis.

BACKGROUND: Protein cysteine oxidation is substantially involved in various biological and pathogenic processes, but its implications in pancreatic cancer development remains poorly understood. METHODS AND RESULTS: In this study, we performed a global characterization of protein oxidation targets in PDAC cells through iodoTMT-based quantitative proteomics, which identified over 4300 oxidized cysteine sites in more than 2100 proteins in HPDE6c7 and PANC-1 cells. Among them, 1715 cysteine residues were shown to be differentially oxidized between HPDE6c7 and PANC-1 cells. Also, charged amino acids including aspartate, glutamate and lysine were significantly overrepresented in flanking sequences of oxidized cysteines. Differentially oxidized proteins in PANC-1 cells were enriched in multiple cancer-related biological processes and signaling pathways. Specifically, the HIF-1 signaling proteins exhibited significant oxidation alterations in PANC-1 cells, and the reduced PHD2 oxidation in human PDAC tissues was correlated with lower survival time in pancreatic cancer patients. CONCLUSION: These investigations provided new insights into protein oxidation-regulated signaling and biological processes during PDAC pathogenesis, which might be further explored for pancreatic cancer diagnosis and treatment.

Neutrophil CD64 index as a new early predictive biomarker for infected pancreatic necrosis in acute pancreatitis.

OBJECTIVE: Infectious pancreatic necrosis (IPN) is a serious complication of acute pancreatitis, and early recognition and timely intervention are the keys to improving clinical outcomes. The purpose of this study was to investigate the predictive capacity of the neutrophil CD64 index (nCD64 index) on IPN in patients with acute pancreatitis METHODS: This study comprises two independent cohorts: the training cohort consisted of 202 patients from Hunan Provincial People's Hospital, and the validation cohort consisted of 100 patients from Changsha Central Hospital. Peripheral blood samples were collected on the day of admission and on the 3rd, 5th, 7th, and 10th days of hospitalization, and the nCD64 index was detected by flow cytometry. Additionally, relevant clinical characteristics and laboratory biomarkers were collected and analyzed. RESULTS: We observed that nCD64 index on admission was significantly higher in the IPN group than Non-IPN group (p < 0.001). In the training cohort, a higher occurrence rate of IPN was observed in the high nCD64 index group compared to the moderate and low nCD64 index group (p < 0.001). Further analysis showed that nCD64 index was significant positive correlated with the incidence rate of IPN (p < 0.001, correlation coefficient = 0.972). Furthermore, logistic regression analysis showed that high expression of the nCD64 index on admission was a risk factor for the occurrence of IPN (OR = 2.971, p = 0.038). We further found that the nCD64 index of IPN patients was significantly higher than the Non-IPN patients on the days 1, 3, and 5 after admission, and the nCD64 index of IPN patients before and after the onset (p < 0.05). At the same time, this study revealed that the nCD64 index on admission showed good predictive efficacy for IPN (AUC = 0.859, sensitivity = 80.8%, specificity = 87.5%), which was comparable to APACHE II score. And this finding was further validated in an independent cohort of 100 participants (AUC = 0.919, Sensitivity = 100.0%, Specificity = 76.6%). CONCLUSION: This study demonstrated the clinical value of nCD64 index in patients with IPN patients for the first time through two independent cohort studies. The nCD64 index can be used as an early prediction and risk assessment tool for the occurrence of IPN, contributing to the improvement of patient outcomes and efficiency of medical resource allocation.

Serum metabolomics study for acute attack of chronic pancreatitis.

BACKGROUND & AIMS: Chronic pancreatitis (CP) is an inflammatory disease characterized by irreversible changes. However, acute CP attacks can lead to various complications and affect patient prognosis. Therefore, this study aimed to identify reliable candidate metabolic biomarkers for diagnosing acute CP attacks and complement candidate diagnostic markers for CP. METHODS: A total of 139 serum specimens were prospectively included in three consecutive exploratory, identification, and validation studies. All samples were analyzed for candidate diagnostic biomarkers and metabolic pathways using a liquid chromatography-mass spectrometer. RESULTS: Serum metabolic profiles differed between patients with CP and non-pancreatic disease controls, and 239 potential metabolic biomarkers for diagnosing CP were identified. Based on identification and validation studies, Diacylglycerol(16:0/18:4), 16-F1-PhytoP, N-(hexacosanoyl)-tetradecasphing-4-enine, carnosic acid, and Auxin b were identified as biomarkers for distinguishing acute attacks from non-acute attacks in patients with CP. The area under the curve of the Diacylglycerol(16:0/18:4) was 0.969 (95% confidence interval, 0.869-1) in the validation study. CONCLUSIONS: To the best of our knowledge, this is the first prospective cohort study to identify and validate a metabolomic signature in serum for diagnosing acute attacks of CP. In addition, our study identified 239 potential biomarkers for CP diagnosis.

Fabrication and application of nanoporous anodic aluminum oxide: a review.

Due to the unique optical and electrochemical properties, large surface area, tunable properties, and high thermal stability, nanoporous anodic aluminum oxide (AAO) has become one of the most popular materials with a large potential to develop emerging applications in numerous areas, including biosensors, desalination, high-risk pollutants detection, capacitors, solar cell devices, photonic crystals, template-assisted fabrication of nanostructures, and so on. This review covers the mechanism of AAO formation, manufacturing technology, the relationship between the properties of AAO and fabrication conditions, and applications of AAO. Properties of AAO, like pore diameter, interpore distance, wall thickness, and anodized aluminum layer thickness, can be fully controlled by fabrication conditions, including electrolyte, applied voltage, anodizing and widening time. Generally speaking, the pore diameter of AAO will affect its specific application to a large extent. Moreover, manufacturing technology like one/two/multi step anodization, nanoimprint lithography anodization, and pulse/cyclic anodization also have a major impact on overall array arrangement. The review aims to provide a perspective overview of the relationship between applications and their corresponding AAO pore sizes, systematically. And the review also focuses on the strategies by which the structures and functions of AAO can be utilized.

A flower-inspired divergent light-trapping structure with quasi-spherical symmetry towards a high-performance flexible photodetector.

Molybdenum disulfide (MoS2) has received widespread attention in recent years due to its exciting properties. However, the practical applications of MoS2 in optoelectronic devices are impeded by the power supply problem, the lack of flexibility, and the low light absorption for planar nanosheets and nanosheet arrays. Inspired by the elaborate architecture of the flower Tagetes erecta L., in this work, a self-assembled divergent MoS2 nanoflower (MoS2_F) with quasi-spherical symmetry is successfully synthesized by a facile one-step hydrothermal method. It is of significance that coupled with asymmetric silver electrodes and packaged by polymethyl methacrylate (PMMA), a self-powered flexible photodetector (PD) based on MoS2_F is actualized and shows an excellent flexible photoresponse performance at zero bias voltage. The divergent structure with quasi-spherical symmetry enables the MoS2_F to achieve strong broadband and omnidirectional absorption (92.7%) and ensures that the MoS2_F maintains the same physical contact on a different bending degree. Intriguingly, excellent flexibility and stability have been achieved as MoS2_F PD retains 91.4% of the initial efficiency even when bent to 151° and retains 92.5% of the initial efficiency even after 1000 bending cycles. Therefore, by a low-cost process, this work demonstrates an innovative avenue to fabricate a self-powered flexible photodetector with excellent light absorption, broadband response, flexibility, and stability, which is of great practical significance for optoelectronic applications in various environments.

Gut Microbiota Dysbiosis Associated with Bile Acid Metabolism in Neonatal Cholestasis Disease.

Neonatal cholestasis disease (NCD) is a complex and easily mis-diagnosed condition. We analyzed microbiota community structure in feces and measured short-chain fatty acids, bile acids (BAs) and liver function of 12 healthy, 13 NCD, and 13 treated infants after diagnosis. Based on 16S rRNA gene amplicon sequencing and gas-chromatographic-mass-spectrometric analysis of secondary BAs, we identified microbial genera and metabolites that associate with abnormal bile secretion. Streptococcus gallolyticus and Parabacteroides distasonis, and Lactobacillus gasseri had higher relative abundance in healthy and NCD infants respectively. Compared to NCD patients, healthy infants had higher LCA, CDCA and GCDCA fecal concentrations. The three microbial species and three secondary bile acids were selected as potential non-invasive combined biomarkers to diagnose NCD. We propose that microbiota-metabolite combined biomarkers could be used for diagnosis of NCD, and this may contribute to improved early clinical diagnosis of NCD in the future.

[Levels of short-chain fatty acids in enterobacteria-related metabolites in the feces of infants with cholestatic hepatopathy].

OBJECTIVE: To compare the levels of short-chain fatty acids in enterobacteria-related metabolites in feces between infants with cholestatic hepatopathy and healthy infants. METHODS: Thirty infants with cholestatic hepatopathy were enrolled in this study as the disease group, while 30 healthy infants were enrolled as the control group. Fecal specimens were collected from the disease group before and after treatment and from the control group. Gas chromatography was used to quantitatively determine the content of short-chain fatty acids in the feces of both groups including acetic acid, propionic acid, butyric acid, isobutyric acid, and isovaleric acid. RESULTS: There were no significant differences in the concentrations of acetic acid and propionic acid between the control and disease groups before and after treatment, as well as no significant changes in the two markers in the disease group after treatment (P>0.05). The disease group had a significantly increased concentration of butyric acid after treatment (P<0.05). The concentrations of isobutyric acid and isovaleric acid in the control group were significantly higher than those in the disease group before and after treatment (P<0.05). CONCLUSIONS: Intestinal protein metabolites in infants with cholestatic hepatopathy are significantly different from those in healthy infants, whereas there is no significant difference with respect to carbohydrate metabolites.

[Analysis of essential oil from Mahonia duclouxiana].

OBJECTIVE: To analyze the compositions of essential oil from Mahonia duclouxiana. METHODS: The essential oil was extracted by steam distillation, its chemical components were analyzed by GC-MS, and principal component was confirmed by GC. RESULTS: 80 peaks were detected and 41 components have been identified, which made up more than 90% of total essential oil. The major component was 4-Terpineol (43.73%), the other high content components were alpha-Terpineol (5.23%), (Z)-3-Hexen-1-ol (4.78%), Linalool (4.04%), etc. CONCLUSION: The chemical components of essential oil of from Mahonia duclouxiana by GC-MS for the first time. This study provided science basis for further research development of Mahonia duclouxiana.