| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
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| 4. |
- Fang, Evandro F., et al.
(author)
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A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research, long-term care, policy and social networks.
- 2020
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In: Ageing Research Reviews. - : Elsevier BV. - 1568-1637. ; 64
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Journal article (peer-reviewed)abstract
- One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems. Major healthcare challenges involved with caring for the elderly in China include the management of chronic non-communicable diseases (CNCDs), physical frailty, neurodegenerative diseases, cardiovascular diseases, with emerging challenges such as providing sufficient dental care, combating the rising prevalence of sexually transmitted diseases among nursing home communities, providing support for increased incidences of immune diseases, and the growing necessity to provide palliative care for the elderly. At the governmental level, it is necessary to make long-term strategic plans to respond to the pressures of an ageing society, especially to establish a nationwide, affordable, annual health check system to facilitate early diagnosis and provide access to affordable treatments. China has begun work on several activities to address these issues including the recent completion of the of the Ten-year Health-Care Reform project, the implementation of the Healthy China 2030 Action Plan, and the opening of the National Clinical Research Center for Geriatric Disorders. There are also societal challenges, namely the shift from an extended family system in which the younger provide home care for their elderly family members, to the current trend in which young people are increasingly migrating towards major cities for work, increasing reliance on nursing homes to compensate, especially following the outcomes of the ‘one child policy’ and the ‘empty-nest elderly’ phenomenon. At the individual level, it is important to provide avenues for people to seek and improve their own knowledge of health and disease, to encourage them to seek medical check-ups to prevent/manage illness, and to find ways to promote modifiable health-related behaviors (social activity, exercise, healthy diets, reasonable diet supplements) to enable healthier, happier, longer, and more productive lives in the elderly. Finally, at the technological or treatment level, there is a focus on modern technologies to counteract the negative effects of ageing. Researchers are striving to produce drugs that can mimic the effects of ‘exercising more, eating less’, while other anti-ageing molecules from molecular gerontologists could help to improve ‘healthspan’ in the elderly. Machine learning, ‘Big Data’, and other novel technologies can also be used to monitor disease patterns at the population level and may be used to inform policy design in the future. Collectively, synergies across disciplines on policies, geriatric care, drug development, personal awareness, the use of big data, machine learning and personalized medicine will transform China into a country that enables the most for its elderly, maximizing and celebrating their longevity in the coming decades. This is the 2nd edition of the review paper (Fang EF et al., Ageing Re. Rev. 2015).
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| 5. |
- Wan, Cheng-Liang, et al.
(author)
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Dynamics of slow electrons transmitting through straight glass capillary and tapered glass capillary
- 2016
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In: Wuli xuebao. - : Acta Physica Sinica, Chinese Physical Society and Institute of Physics, Chinese Academy of Sciences. - 1000-3290. ; 65:20
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Journal article (peer-reviewed)abstract
- It has been found that the transmission rate of the electrons through insulating capillaries as a function of time/incident charge is not the same as that of the ions. The question arises that by using the electrons, if the negative charge patches can be formed to facilitate the transmission of the following electrons, thereby substantiating that the so-called guiding effect works also for electrons. This study aims to observe the time evolutions of the transmission of electrons through a straight glass tube and a tapered glass capillary. This will reveal the details of how and (or) if the negative charge patches can be formed when the electrons transport through them. In this work, a set of MCP/phosphor two-dimensional detection system based on Labview platform is developed to obtain the time evolution of the angular distribution of the transmitted electrons. The pulsed electron beams are obtained to test our detection system. The time evolution of the angular profile of 1.5 keV electrons transmitting through the glass tube/capillary is observed. The transmitted electrons are observed on the detector for a very short time and disappear for a time and then appear again for both the glass tube and tapered glass capillary, leading to an oscillation. The positive charge patches are formed in the insulating glass tube and tapered glass capillary since the secondary electron emission coefficient for the incident energy is larger than 1. It is due to the fact that fast discharge of the deposited charge leads to the increase of the transmission rate, while the fast blocking of the incident electrons due to the deposited positive charge leads to the decrease of the transmission rate. The geometrical configuration of the taper glass capillary tends to make the secondary electrons deposited at the exit part to form the negative patches that facilitate the transmission of electrons. This suggests that if the stable transmission needs to be reached for producing the electron micro-beam by using tapered glass capillaries, the steps must be taken to have the proper grounding and shielding of the glass capillaries and tubes. Our results show a difference in transmission through the insulating capillary between electrons and highly charged ions.
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| 6. |
- Wang, Yong, et al.
(author)
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mRNA expression of minichromosome maintenance 2 in colonic adenoma and adenocarcinoma
- 2009
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In: EUROPEAN JOURNAL OF CANCER PREVENTION. - 0959-8278. ; 18:1, s. 40-45
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Journal article (peer-reviewed)abstract
- As proliferation is essential for Progression from normal cells to tumor, certain markers specific to proliferating cells may permit detection of premalignant lesions. Here, we aimed to evaluate the possible value of a proliferation marker, minichromosome maintenance 2 (MCM2), in the early diagnosis of colorectal cancer, by analyzing the difference in MCM2 expression among normal mucosa, adenoma, and adenocarcinoma, and investigating the relationship of MCM2 expression in adenomas with clinicopathologic variables. Using immunohistochemistry and real-time reverse transcription-PCR, we observed that the expression of MCM2 protein was present on basal third to half of colonic crypts in normal mucosa, whereas throughout the epithelium in adenomas and adenocarcinomas, the expression of MCM2 mRNA in adenocarcinomas was significantly higher than in adenomas (P=0.001), whereas the difference between adenoma and normal mucosa was not significant (P=0.184); we also found that the expression of MCM2 mRNA tended to be increased in the adenomas with high-grade dysplasia, or in older patients, respectively, compared with those with low-grade dysplasia, and younger patients. These results suggested the potential value of MCM2 in early diagnosis of colorectal cancer.
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| 7. |
- Fan, Chuan-Wen, et al.
(author)
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Expression profile, molecular functions, and prognostic significance of miRNAs in primary colorectal cancer stem cells
- 2021
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In: Aging. - : Impact Journals LLC. - 1945-4589. ; 13:8, s. 12067-12085
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Journal article (peer-reviewed)abstract
- MicroRNAs (miRNAs) are known to drive the pathogenesis of colorectal cancer (CRC) via the regulation of cancer stem cells (CSCs). We studied the miRNA expression profile of primary CSCs isolated from patients with CRC (pCRCSCs). Compared to pCRCSC-derived differentiated cells, 98 differentially expressed miRNAs were identified in pCRCSCs. Target genes encoding pCRCSC-related miRNAs were identified using a combination of miRNA target databases and miRNA-mRNA regulatory networks from the same patient. The pCRCSC-related miRNA target genes were associated with pathways contributing to malignant phenotypes, including I-kappa B kinase/NF-kappa B signaling, signal transduction by p53 class mediator, Ras signaling, and cGMP-PKG signaling. The pCRCSC-related miRNA expression signature was independently associated with poor overall survival in both the training and validation cohorts. We have thus identified several pCRCSC-related miRNAs with oncogenic potential that could serve as prognostic biomarkers for CRC.
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| 8. |
- Han, Yang, et al.
(author)
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X-radiation inhibits histone deacetylase 1 and 2, upregulates Axin expression and induces apoptosis in non-small cell lung cancer
- 2012
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In: Radiation Oncology. - : BioMed Central. - 1748-717X. ; 7:183
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Journal article (peer-reviewed)abstract
- BackgroundHistone deacetylase (HDAC) plays an important role in the deacetylation of histone, which can alter gene expression patterns and affect cell behavior associated with malignant transformation. The aims of this study were to investigate the relationships between HDAC1, HDAC2, clinicopathologic characteristics, patient prognosis and apoptosis, to clarify the mechanism of upregulation of the Axis inhibitor Axin (an important regulator of the Wnt pathway) by X-radiation and to elucidate the effect of siRNA on radiation therapy of non-small cell lung cancer (NSCLC).MethodsHDAC1 and HDAC2 expression levels were measured by immunohistochemistry and reverse transcription PCR. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling and fluorescence activated cell sorting. BE1 cells expressing Axin were exposed to 2 Gy of X-radiation.ResultsExpression of HDAC1 and that of HDAC2 were correlated, and significantly higher in NSCLC tissues than in normal lung tissues (P < 0.05). HDAC1 and HDAC2 expression was correlated with pTNM stage and negatively correlated with differentiation of NSCLC and apoptotic index (P < 0.05). The prognosis of patients with low expression of HDAC1 and HDAC2 was better than that of those with high expression. X-radiation and siRNA inhibited HDAC1 and HDAC2 expression in NSCLC cells and Axin levels were significantly higher in BE1 cells.ConclusionsX-radiation and siRNA inhibit expression of HDAC1 and HDAC2, weaken the inhibitory effect of HDAC on Axin, upregulate Axin expression and induce apoptosis of lung cancer cells. Inhibition of HDAC1 and HDAC2 is a means of enhancing the radiosensitivity of NSCLC.
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| 9. |
- Qian, Li-Bing, et al.
(author)
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Transmission of electrons through the conical glass capillary with the grounded conducting outer surface
- 2017
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In: Wuli xuebao. - : Acta Physica Sinica, Chinese Physical Society and Institute of Physics, Chinese Academy of Sciences. - 1000-3290. ; 66:12
-
Journal article (peer-reviewed)abstract
- The transmission of 1.5 keV-electrons through a conical glass capillary is reported. This study aims to understand the so-called guiding effect for the negatively charged particles (e.g. electrons). The guiding mechanism is understood quite well with positively charged particles in particular highly charged ions, but not clear with electrons, i. e., even the basic scheme mediated by the existence of negative charge patches to guide the electrons is still somewhat controversial.. The study of the charging-up dynamics causing the electrons transport inside the capillary will shed light on this issue. In order to perform this, a data acquisition system has been setup to follow the time evolution of the two-dimensional angular distribution of the transmitted electrons. The electrons are detected by the multi-channel plate (MCP) detector with a phosphor screen. The image from the phosphor screen is recorded by a charge-coupled device camera. The timing signals for the detected events are extracted from the back stack of the MCP detector and recorded by the data acquisition system, synchronized with the acquired images. The electron beam has a size of 0.5 mm x 0.5 mm and a divergence of less than 0.35.. The inner diameter of the straight part of the capillary is 1.2 mm and the exit diameter is 225 mu m. A small conducting aperture of 0.3 mm in diameter is placed at the entrance of the capillary. Two-dimensional angular distribution of the transmitted electrons through conical glass capillary and its time evolution are measured. The results show that the transmission rate decreases and reaches to a constant value for the completely discharged glass capillary with time going by. The centroid of the angular distribution moves to an asymptotic value while the width remains unchanged. These transmission characteristics are different from those indicated in our previous work (2016 Acta Phys: Si n: 65 204103). The difference originates from the different manipulations of the capillary outer surface. A conducting layer is coated on the outer surface of the capillary and grounded in this work. This isolates various discharge/charge channels and forms a new stable discharge channel. The transmission rate as a function of the tilt angle shows that the allowed transmission occurs at the tilt angle limited by the geometrical factors, i. e., the geometrical opening angle given by the aspect ratio as well as the beam divergence. The transmission characteristics suggest that most likely there are formed no negative patches to facilitate the electron transmission through the glass capillary at this selected beam energy. It is different from that of highly charged ions, where the formation of the charge patches prohibits the close collisions between the following ions and guides them out of the capillary.
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| 10. |
- Tian, Chao, et al.
(author)
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Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancer patients
- 2007
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In: World Journal of Gastroenterology. - 1007-9327 .- 2219-2840. ; 13:28, s. 3878-3882
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Journal article (peer-reviewed)abstract
- Aim: To clarify the expression change of Wnt-induced secreted protein-1 (WISP-1) in human rectal cancer and to determine whether it is correlated with invasion and metastasis of human rectal cancer. Methods: Eighty-six paired samples of rectal cancer and surgically resected distant normal rectal tissue were collected and allocated into cancer group and control group respectively. WISP-1 mRNA was detected by relative quantitative real-time RT-PCR and WISP-1 protein was examined by immunohistochemical staining. Results: WISP-1 gene overexpression was found in 65% (56/86) primary rectal cancers, 2-30 times that of the level in normal matched rectal tissues (P = 0.001). The mRNA expression level was correlated with Duke's staging, histological differentiation grade and lymph node status. The WISP-1 protein expression was in accordance with mRNA expression level. The positive degree of immunohistochemical staining in the cancer group (1.40 ± 0.35) was different from that in control group (1.04 ± 0.08, P < 0.001). Moreover, in cancer group the positive staining degree in high-level mRNA cancers (1.46 ± 0.37, n = 56) was higher than that in low-level mRNA (1.28 ± 0.28, n = 30, P = 0.018). Conclusion: Aberrant levels of WISP-1 expression may play a role in rectal tumorigenesis. WISP-1 may be used as a specific clinical diagnosis and prognosis marker in rectal cancer. © 2007 WJG. All rights reserved.
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| 11. |
- Chen, Guang, et al.
(author)
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NeuroIV : Neuromorphic Vision Meets Intelligent Vehicle Towards Safe Driving With a New Database and Baseline Evaluations
- 2022
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In: IEEE transactions on intelligent transportation systems (Print). - : Institute of Electrical and Electronics Engineers (IEEE). - 1524-9050 .- 1558-0016. ; 23:2, s. 1171-1183
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Journal article (peer-reviewed)abstract
- Neuromorphic vision sensors such as the Dynamic and Active-pixel Vision Sensor (DAVIS) using silicon retina are inspired by biological vision, they generate streams of asynchronous events to indicate local log-intensity brightness changes. Their properties of high temporal resolution, low-bandwidth, lightweight computation, and low-latency make them a good fit for many applications of motion perception in the intelligent vehicle. However, as a younger and smaller research field compared to classical computer vision, neuromorphic vision is rarely connected with the intelligent vehicle. For this purpose, we present three novel datasets recorded with DAVIS sensors and depth sensor for the distracted driving research and focus on driver drowsiness detection, driver gaze-zone recognition, and driver hand-gesture recognition. To facilitate the comparison with classical computer vision, we record the RGB, depth and infrared data with a depth sensor simultaneously. The total volume of this dataset has 27360 samples. To unlock the potential of neuromorphic vision on the intelligent vehicle, we utilize three popular event-encoding methods to convert asynchronous event slices to event-frames and adapt state-of-the-art convolutional architectures to extensively evaluate their performances on this dataset. Together with qualitative and quantitative results, this work provides a new database and baseline evaluations named NeuroIV in cross-cutting areas of neuromorphic vision and intelligent vehicle.
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| 12. |
- Chen, Ke-Ling, et al.
(author)
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Effects of Tocilizumab on Experimental Severe Acute Pancreatitis and Associated Acute Lung Injury
- 2016
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In: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 44:8, s. E664-E677
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Journal article (peer-reviewed)abstract
- Objective: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. Design: Randomized experiment. Setting: Research laboratory at a university hospital. Subject: Experimental severe acute pancreatitis in rats. Interventions: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). Measurements and Main Results: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-kappa B and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration. Conclusions: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.
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| 13. |
- Chen, Zhi, et al.
(author)
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Large-Area Crystalline Zeolitic Imidazolate Framework Thin Films
- 2021
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In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:25, s. 14124-14130
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Journal article (peer-reviewed)abstract
- We report that continuous MOF films with highly controlled thickness (from 44 to 5100 nm) can be deposited over length scales greater than 80 centimeters by a facile, fast, and cost-effective spray-coating method. Such success relies on our discovery of unprecedented perfectly dispersed colloidal solutions consisting of amorphous MOF nanoparticles, which we adopted as precursors that readily converted to the crystalline films upon low-temperature in situ heating. The colloidal solutions allow for the fabrication of compact and uniform MOF films on a great deal of substrates such as fluorine-doped tin oxide, glass, SiO2, Al2O3, Si, Cu, and even flexible polycarbonate, widening their technological applications where substrates are essential. Despite the present work focuses on the fabrication of uniform cobalt-(2-methylimidazole)2 and zinc-(2-methylimidazole)2 films, our findings mark a great possibility in producing other high-quality MOF thin films on a large scale.
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| 14. |
- Cui, Hong-Guang, et al.
(author)
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Synthesis, structures and electrochemical properties of hydroxyl- and pyridyl-functionalized diiron azadithiolate complexes
- 2007
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In: Polyhedron. - : Elsevier BV. - 0277-5387 .- 1873-3719. ; 26:4, s. 904-910
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Journal article (peer-reviewed)abstract
- The hydroxyl- and pyridyl-functionalized diiron azadithiolate complexes [[(mu-SCH2)(2)N(CH2CH2OH)}Fe-2(CO)(6)] (1) and [{(mu-SCH2)(2)N(CH2CH2OOCPy)} Fe-2(CO)(6)] (Py = pyridyl) (2) were prepared as biomimetic models of the active site of Fe-only hydrogenases. Both complexes were characterized by MS, IR, H-1 NMR spectra and elemental analysis. The molecular structures of 1 and 2 were determined by single crystal X-ray analysis. A network is constructed by intermolecular H-bonds in the crystals of 1. An S center dot center dot center dot O intermolecular contact was found in the crystals of 2, which is scarcely found for organometallic complexes. Cyclic voltammograms of 1 and 2 were studied to evaluate their redox properties.
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| 15. |
- Fan, Chuanwen, et al.
(author)
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Mismatch repair protein deficiency and its implications on distant metastasis in colorectal cancer : A comprehensive analysis
- 2024
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In: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 13:7
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Journal article (peer-reviewed)abstract
- Background: While previous studies have indicated variability in distant metastatic potential among different mismatch repair (MMR) states in colorectal cancer (CRC), their findings remain inconclusive, especially considering potential differences across various ethnic backgrounds. Furthermore, the gene regulatory networks and the underlying mechanisms responsible for these variances in metastatic potential across MMR states have yet to be elucidated.Methods: We collected 2058 consecutive primary CRC samples from the South West of China and assessed the expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) using immunohistochemistry. To explore the inconsistencies between different MMR statuses and recurrence, we performed a meta-analysis. To delve deeper, we employed Weighted Gene Co-expression Network Analysis (WGCNA), ClueGo, and iRegulon, pinpointing gene expression networks and key regulatory molecules linked to metastasis and recurrence in CRC. Lastly, both univariate and multivariate Cox regression analyses were applied to determine the impact of core regulatory molecules on metastasis.Results: Of the samples, 8.2% displayed deficient MMR (dMMR), with losses of MLH1 and PSM2 observed in 40.8% and 63.9%, respectively. A unique 24.3% isolated loss of PMS2 without concurrent metastasis was identified, a result that diverges from established literature. Additionally, our meta-analysis further solidifies the reduced recurrence likelihood in dMMR CRC samples compared to proficient MMR (pMMR). Two gene expression networks tied to distant metastasis and recurrence were identified, with a majority of metastasis-related genes located on chromosomes 8 and 18. An IRF1 positive feedback loop was discerned in the metastasis-related network, and IRF1 was identified as a predictive marker for both recurrence-free and distant metastasis-free survival across multiple datasets.Conclusion: Geographical and ethnic factors might influence peculiarities in MMR protein loss. Our findings also highlight new gene expression networks and crucial regulatory molecules in CRC metastasis, enhancing our comprehension of the mechanisms driving distant metastasis.
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| 16. |
- Fan, Chuan-Wen, et al.
(author)
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Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals
- 2020
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In: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 9
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Journal article (peer-reviewed)abstract
- Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear.Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO. Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC.Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively.
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| 17. |
- Liu, Yong, et al.
(author)
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Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity
- 2017
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In: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889. ; 8
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Journal article (peer-reviewed)abstract
- Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of L-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor kappa B (NF-kappa B) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-kappa B activation and less release of TNF-alpha and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
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| 18. |
- Liu, Yong, et al.
(author)
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Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury
- 2016
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In: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : AMER PHYSIOLOGICAL SOC. - 0193-1857 .- 1522-1547. ; 310:5, s. G303-G309
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Journal article (peer-reviewed)abstract
- Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-kappa B activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-alpha, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-kappa B activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-kappa B activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.
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| 19. |
- Meng, Wen-Jian, et al.
(author)
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MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer
- 2015
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In: Medicine. - : Lippincott Williams & Wilkins. - 0025-7974 .- 1536-5964. ; 94:32
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Journal article (peer-reviewed)abstract
- The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P=0.012), coexistence of adenoma (P=0.012), microsatellite instability (P=0.024), and less glucose transporter 1 (P=0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.
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| 20. |
- Meng, Wen-Jian, et al.
(author)
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Special AT-rich sequence binding protein 1 expression correlates with response to preoperative radiotherapy and clinical outcome in rectal cancer
- 2015
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In: Cancer Biology & Therapy. - : Taylor & Francis. - 1538-4047 .- 1555-8576. ; 16:12, s. 1738-1745
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Journal article (peer-reviewed)abstract
- Our recent study showed the important role of special AT-rich sequence binding protein 1 (SATB1) in the progression of human rectal cancer. However, the value of SATB1 in response to radiotherapy (RT) for rectal cancer hasn't been reported so far. Here, SATB1 was determined using immunohistochemistry in normal mucosa, biopsy, primary cancer, and lymph node metastasis from 132 rectal cancer patients: 66 with and 66 without preoperative RT before surgery. The effect of SATB1 knockdown on radiosensitivity was assessed by proliferation-based assay and clonogenic assay. The results showed that SATB1 increased from normal mucosa to primary cancer, whereas it decreased from primary cancer to metastasis in non-RT patients. SATB1 decreased in primary cancers after RT. In RT patients, positive SATB1 was independently associated with decreased response to preoperative RT, early time to metastasis, and worse survival. SATB1 negatively correlated with ataxia telangiectasia mutated (ATM) and pRb2/p130, and positively with Ki-67 and Survivin in RT patients, and their potential interaction through different canonical pathways was identified in network ideogram. Taken together, our findings disclose for the first time that radiation decreases SATB1 expression and sensitizes cancer cells to confer clinical benefit of patients, suggesting that SATB1 is predictive of response to preoperative RT and clinical outcome in rectal cancer.
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| 21. |
- Pang, Yun-Jie, et al.
(author)
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Theoretical Study of the Catalytic Mechanism of the Cu-Only Superoxide Dismutase
- 2023
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In: Journal of Physical Chemistry B. - 1520-6106 .- 1520-5207. ; 127:21, s. 4800-4807
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Journal article (peer-reviewed)abstract
- The catalytic mechanisms for the wild-type and the mutated Cu-only superoxide dismutase were studied using the hybrid density functional B3LYP and a quantum chemical cluster approach. Optimal protonation states of the active site were examined for each stage of the catalytic cycle. For both the reductive and the oxidative half-reactions, the arrival of the substrate O-2(center dot-) was found to be accompanied by a chargecompensating H+ with exergonicities of -15.4 kcal center dot mol and -4.7 kcal center dot mol, respectively. The second-sphere Glu-110 and first-sphere His-93 were suggested to be the transient protonation site for the reductive and the oxidative half-reactions, respectively, which collaborates with the hydrogen bonding water chain to position the substrate near the redox-active copper center. For the reductive half-reaction, the rate-limiting step was found to be the inner-sphere electron transfer from the partially coordinated O-2(center dot-) to Cu-II with a barrier of 8.1 kcal center dot mol. The formed O-2 is released from the active site with an exergonicity of -14.9 kcal center dot mol. For the oxidative half-reaction, the inner-sphere electron transfer from CuI to the partially coordinated O-2(center dot-) was found to be accompanied by the proton transfer from the protonated His-93 and barrierless. The rate-limiting step was found to be the second proton transfer from the protonated Glu-110 to HO2 with a barrier of 7.3 kcal center dot mol. The barriers are reasonably consistent with experimental activities, and a proton-transfer rate-limiting step in the oxidative half-reaction could explain the experimentally observed pH-dependence. For the E110Q CuSOD, Asp-113 was suggested to be likely to serve as the transient protonation site in the reductive half-reaction. The rate-limiting barriers were found to be 8.0 and 8.6 kcal center dot mol, respectively, which could explain the slightly lower performance of E110X mutants. The results were found to be stable, with respect to the percentage of exact exchange in B3LYP.
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| 22. |
- Wang, Guo-dong, et al.
(author)
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The genomics of selection in dogs and the parallel evolution between dogs and humans
- 2013
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 4, s. 1860-
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Journal article (peer-reviewed)abstract
- The genetic bases of demographic changes and artificial selection underlying domestication are of great interest in evolutionary biology. Here we perform whole-genome sequencing of multiple grey wolves, Chinese indigenous dogs and dogs of diverse breeds. Demographic analysis show that the split between wolves and Chinese indigenous dogs occurred 32,000 years ago and that the subsequent bottlenecks were mild. Therefore, dogs may have been under human selection over a much longer time than previously concluded, based on molecular data, perhaps by initially scavenging with humans. Population genetic analysis identifies a list of genes under positive selection during domestication, which overlaps extensively with the corresponding list of positively selected genes in humans. Parallel evolution is most apparent in genes for digestion and metabolism, neurological process and cancer. Our study, for the first time, draws together humans and dogs in their recent genomic evolution.
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| 23. |
- Wang, Mo-Jin, et al.
(author)
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Prognostic significance and molecular features of colorectal mucinous adenocarcinomas : A strobe-compliant study
- 2015
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In: Medicine. - : Lippincott Williams & Wilkins. - 0025-7974 .- 1536-5964. ; 94:51
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Journal article (peer-reviewed)abstract
- Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973 2011), and Linkoping Cancer (LC, 1972-2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P < 0.001) and LC (46.9% vs 27.7%, P < 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P < 0.001; LC, P = 0.026), prominently in stage III (SEER, P < 0.001; P=0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057-1.096; P < 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493-10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CT, 0.106-1.192; P=0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.
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| 24. |
- Wang, Mo-Jin, et al.
(author)
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The prognostic factors and multiple biomarkers in young patients with colorectal cancer
- 2015
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In: Scientific Reports. - : Nature Publishing Group: Open Access Journals - Option C / Nature Publishing Group. - 2045-2322. ; 5:10645
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Journal article (peer-reviewed)abstract
- The incidence of colorectal cancer (CRC) in young patients (less than= 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linkoping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.
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| 25. |
- Yang, Xi-Xi, et al.
(author)
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Theoretical study of the mechanism of the manganese catalase KatB
- 2019
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In: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 24:1, s. 103-115
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Journal article (peer-reviewed)abstract
- The mechanism of the H2O2 disproportionation catalyzed by the manganese catalase (MnCat) KatB was studied using the hybrid density functional theory B3LYP and the quantum chemical cluster approach. Compared to the previous mechanistic study at the molecular level for the Thermus thermophilus MnCat (TTC), more modern methodology was used and larger models of increasing sizes were employed with the help of the high-resolution X-ray structure. In the reaction pathway suggested for KatB using the Large chemical model, the O-O homolysis of the first substrate H2O2 occurs through a -(1):(1) coordination mode and requires a barrier of 10.9kcal/mol. In the intermediate state of the bond cleavage, two hydroxides form as terminal ligands of the dimanganese cluster at the Mn-2(III,III) oxidation state. One of the two Mn(III)-OH- moieties and a second-sphere tyrosine stabilize the second substrate H2O2 in the second-sphere of the active site via hydrogen bonding interactions. The H2O2, unbound to the metals, is first oxidized into HO2 through a proton-coupled electron transfer (PCET) step with a barrier of 9.5kcal/mol. After the system switches to the triplet surface, the uncoordinated HO2 replaces the product water terminally bound to the Mn(II) and is then oxidized into O-2 spontaneously. Transition states with structural similarities to those obtained for TTC, where -(2)-OH-/O2- groups play important roles, were found to be higher in energy.
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| 26. |
- Zhu, Yan-He, et al.
(author)
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Efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure
- 2019
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In: Current medical science. - : Springer. - 2096-5230 .- 2523-899X. ; 39:2, s. 237-242
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Journal article (peer-reviewed)abstract
- Few effective treatments for chronic Keshan disease have been available till now. The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive. This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up. A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years. Of the 302 chronic Keshan disease patients, 170 (56.3%) were given selenium supplementation until the end point of follow-up. Cox proportional hazards regression models were used to identify the independent predictors of cardiac events. Our results showed that during the follow-up, there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group (101/170, 59.4%) and 98 in non-selenium supplementation group (98/132, 74.2%). Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death (HR 0.39, 95% CI 0.28-0.53) after adjustment for baseline age, sex, cigarette smoking, family history of Keshan disease, body mass index (BMI), heart rate, electrocardiogram (ECG) abnormalities, blood pressure, initial cardiothoracic ratio, left ventricular ejection fractions (LVEF) and whole-blood selenium concentration. Our ten-year follow-up analysis indicated that selenium supplementation, specifically combined with the use of angiotensin-converting enzyme inhibitor and beta blocker therapy, improved the survival of patients with chronic Keshan disease with congestive heart failure. BMI, selenium deficiency, male, combined ECG abnormalities, LVEF, and fast heart rate increased the risk of cardiac events.
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