NCACO-score: An effective main-chain dependent scoring function for structure modeling

<p>Abstract</p> <p>Background</p> <p>Development of effective scoring functions is a critical component to the success of protein structure modeling. Previously, many efforts have been dedicated to the development of scoring functions. Despite these efforts, development of an effective scoring function that can achieve both good accuracy and fast speed still presents a grand challenge.</p> <p>Results</p> <p>Based on a coarse-grained representation of a protein structure by using only four main-chain atoms: N, Cα, C and O, we develop a knowledge-based scoring function, called NCACO-score, that integrates different structural information to rapidly model protein structure from sequence. In testing on the Decoys'R'Us sets, we found that NCACO-score can effectively recognize native conformers from their decoys. Furthermore, we demonstrate that NCACO-score can effectively guide fragment assembly for protein structure prediction, which has achieved a good performance in building the structure models for hard targets from CASP8 in terms of both accuracy and speed.</p> <p>Conclusions</p> <p>Although NCACO-score is developed based on a coarse-grained model, it is able to discriminate native conformers from decoy conformers with high accuracy. NCACO is a very effective scoring function for structure modeling.</p

Effects of parenteral nutrition of ω-3 polyunsaturated fatty acid, arginine and glutamine on cellular immune status of patients following liver cancer surgery

Purpose: To study the effects of parenteral nutrition (TPN), ω-3  polyunsaturated fatty acid (PUFA), Larginine (Arg), and glutamine on cellular immunity of patients who have done the liver cancer (LC) surgery.Methods: Seventy-five (75) LC patients were randomly divided into 5  groups (A - E; 15 cases each), group A, B, C, D and E, in which patients were treated with TPN, TPN + fish oil, TPN + Arg, TPN + glutamine, and TPN + ω-3 PUFA + Arg + glutamine, respectively. Before and after surgery, CD3 +, CD4 + and CD8 + were measured by antibody-sensitized erythrocyte rosette test, and IL-6, IL-10 and TNF-a were assayed with double-antibody sandwich enzyme-linked immunoassay (DAS-ELISA). IgA and IgM were measured nephelometrically.Results: The levels of CD3 +, CD4 + and CD8 + in group A showed no  obvious change after surgery (p &gt; 0.05). However, CD3 + and CD4 +  increased in groups B, C and D, while CD8 + decreased in group E (p &lt; 0.05). IL-6 in group E was lower than that in any of the other four groups (p &lt; 0.05). IL-10 in group A was lower than that in groups B, C and D, but lower than in group E (p &lt; 0.05). The levels of TNF-a in groups B and C were lower than those in group A, but higher than that in group E (p &lt; 0.05) but lower than in group D. IgA in group E was higher than in the other groups (p &lt; 0.05), while IgM level in group E was lower than in groups A, B and C (p &lt; 0.05).Conclusion: Immunosuppressive status and cellular immunity of patients  after liver cancer surgery may be improved by a combination therapy of TPN, ω-3 PUFAs, Arg and glutamine.Keywords: Polyunsaturated fatty acid, Arginine, Glutamine, Parenteral nutrition, Hepatoma, Cellular immunit

A novel biomass coated Ag-TiO2 composite as a photoanode for enhanced photocurrent in dye-sensitized solar cells

Natural Science Foundation of Fujian Province of China [2010J01052]; National Natural Science Foundation of China [21036004, 21176203]A novel biomass-coated Ag nanoparticle-modified TiO2 composite was prepared and used as a photoanode in a dye-sensitized solar cell with a high surface area, strong light scattering and efficient electron transport. It was found that syzygium extract has an appreciable effective function as a reducing and stabilizing agent simultaneously. The mean size of the synthesized silver nanoparticles is 4.0 +/- 0.7 nm measured on the TEM images. Residual hydroxyl groups of the biomass on the photoanode improve dye absorption and electron injection efficiency. The syzygium-Ag-TiO2 DSSC exhibits the best performance with a short-circuit current of 11.8 mA cm(-2) corresponding to a photoelectric conversion efficiency of 5.12%, which is higher than the glucose-Ag-TiO2 and UV-Ag-TiO2 DSSCs, and much higher than the blank DSSC

Retrospective study on MGMT methylation status and its clinical significance in gliomas

Background and purpose: Glioma is a common malignant tumor of central nervous system with poor prognosis. Postoperative concurrent chemoradiotherapy with temozolomide (TMZ) is the main treatment for glioma. The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter can predict the sensitivity of glioma patients to TMZ treatment, however its relationship with clinical pathology and how to better predict treatment and prognosis still need further research. The purpose of this study was to analyze the status of MGMT promoter methylation (MGMTmet) in gliomas and its correlation with clinical pathological features and other common molecular abnormalities, and to explore the value of combined analysis of MGMTmet and other molecular abnormalities in predicting the prognosis of glioma and the efficacy of TMZ treatment. Methods: We retrospectively collected clinical and pathological data from 205 glioma patients diagnosed by the Department of Pathology, Fudan University Shanghai Cancer Center from July 2019 to September 2022. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect MGMTmet status. Sanger sequencing was used to detect the mutation of isocitrate dehydrogenase 1 and 2 (IDH1/2) and telomerase reverse transcriptase (TERT) genes. Fluorescence in situ hybridization (FISH) was used to detect the deletion of the short arm of chromosome 1 and the long arm of chromosome 19 (1p19q). Results: Among 205 patients, the incidence of MGMTmet was higher in female patients than in male patients. Compared to glioblastoma (47.3%), astrocytoma (74.1%) and oligodendroglioma (100.0%) were more prone to methylation of the MGMT gene promoter (P&lt;0.05). In MGMTmet group, IDH1 mutation rate and 1p19q co-deletion rate were significantly increased, and methylation of MGMT promoter was correlated with IDH1 mutation and 1p19q co-deletion (P&lt;0.05). Patients with MGMTmet, age less than 55 years, oligodendroglioma, and World Health Organization (WHO) grade 1-3 all showed longer overall survival (OS), and the difference is statistically significant (P&lt;0.05). Compared with individual influencing factors, dual/triple gene combination analysis (MGMTmet/IDH1 mutation or MGMTmet/1p19q co-deletion or MGMTmet/IDH1 mutation/1p19q co-deletion) had better effect for predicting the patient prognosis (P&lt;0.05), with the latter two being independent prognostic factors. Among TMZ treated patients, MGMTmet (MGMTmet/TMZ+) patients had a better prognosis than other groups. If the patients had combined IDH1 mutations, the prognosis of the patients was further improved (P&lt;0.05). Conclusion: MGMTmet is more common in women and patients with oligodendroglioma. It is positively correlated with IDH1 mutation and 1p19q co-deletion. Patients with MGMTmet are associated with better TMZ treatment efficacy and prognosis, and MGMTmet combined with IDH mutations and 1p19q co-deletion analysis have better TMZ treatment efficacy and prognostic implications

Incorporation of Local Structural Preference Potential Improves Fold Recognition

Fold recognition, or threading, is a popular protein structure modeling approach that uses known structure templates to build structures for those of unknown. The key to the success of fold recognition methods lies in the proper integration of sequence, physiochemical and structural information. Here we introduce another type of information, local structural preference potentials of 3-residue and 9-residue fragments, for fold recognition. By combining the two local structural preference potentials with the widely used sequence profile, secondary structure information and hydrophobic score, we have developed a new threading method called FR-t5 (fold recognition by use of 5 terms). In benchmark testings, we have found the consideration of local structural preference potentials in FR-t5 not only greatly enhances the alignment accuracy and recognition sensitivity, but also significantly improves the quality of prediction models

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

TsFSIM: a three-step fast selection algorithm for influence maximisation in social network

Influence maximisation is the problem of selecting a specific number of nodes which can maximise the influence spread of social networks. For its significant practical applications, the influence maximisation problem has been widely used in many fields, such as network marketing and rumour control. However, most existing algorithms tend to select accuracy or efficiency to optimise, which leads to their poor performance. Therefore, a Three-step Fast Selection algorithm for Influence Maximisation (TsFSIM) is proposed in this paper. Firstly, a new method to evaluate nodes' influence spread is proposed, called Influence Estimation Value. Influence Estimation Value (IEV) combines the node's and its neighbours' degree to estimate its influence. This can improve the efficiency of our algorithm. Afterwards, based on IEV, a three-stage filtering strategy is proposed. This strategy can improve the accuracy of our algorithm greatly. Finally, experimental results on seven real-world networks show that the proposed method is more accurate than other methods while keeping competitive efficiency

HBV DNA polymerase regulates tumor cell glycogen to enhance the malignancy of HCC cells

Background:. The essential function of HBV DNA polymerase (HBV-DNA-Pol) is to initiate viral replication by reverse transcription; however, the role of HBV-DNA-Pol in HBV-associated HCC has not been clarified. Glycogen phosphorylase L (PYGL) is a critical regulator of glycogenolysis and is involved in tumorigenesis, including HCC. However, it is unknown whether HBV-DNA-Pol regulates PYGL to contribute to HCC tumorigenesis. Methods:. Bioinformatic analysis, real-time quantitative PCR, western blotting, and oncology functional assays were performed to determine the contribution of HBV-DNA-Pol and PYGL to HCC development and glycolysis. The mechanisms of co-immunoprecipitation and ubiquitination were employed to ascertain how HBV-DNA-Pol upregulated PYGL. Results:. Overexpression of HBV-DNA-Pol enhanced HCC progression in vitro and in vivo. Mechanistically, HBV-DNA-Pol interacted with PYGL and increased PYGL protein levels by inhibiting PYGL ubiquitination, which was mediated by the E3 ligase TRIM21. HBV-DNA-Pol competitively impaired the binding of PYGL to TRIM21 due to its stronger binding affinity to TRIM21, suppressing the ubiquitination of PYGL. Moreover, HBV-DNA-Pol promoted glycogen decomposition by upregulating PYGL, which led to an increased flow of glucose into glycolysis, thereby promoting HCC development. Conclusions:. Our study reveals a novel mechanism by which HBV-DNA-Pol promotes HCC by controlling glycogen metabolism in HCC, establishing a direct link between HBV-DNA-Pol and the Warburg effect, thereby providing novel targets for HCC treatment and drug development

The Retrieval Relationship between Lightning and Maximum Proxy Reflectivity Based on Random Forest

Using the SWAN (Severe Weather Automatic Nowcasting) maximum reflectivity mosaic product and the lightning positioning observations (LPOs) from the ADTD (Advanced Direction and Time of Arrival Detection) system obtained during the 2018–2020 warm season (May to September), adding multi-characteristic LPO parameters in addition to lightning density, the retrieval relationship between lightning and maximum proxy reflectivity, deemed FRST, is constructed by using random forest. The FRST is compared with two empirical relationships from the GSI (Gridpoint Statistical Interpolation) assimilation system, and the results show that the FRST retrieved result better reflects the frequency distribution structure and peak interval of maximum reflectivity. The correlation coefficient between the FRST retrieved result and the observed maximum reflectivity is 0.7037, which is 3.38 (3.12) times greater than that of empirical GSI relationships. The root mean square error and the mean absolute error are 50.85% (28.05%) and 57.15% (35.19%) lower than those for the empirical GSI relationships, respectively. The equitable threat score (ETS) and bias score (BIAS) for FRST are better than those of the empirical GSI relationships in all three maximum reflectivity intervals

A Probabilistic Forecast Algorithm of Nonconvective Turbulence over the Tibetan Plateau

The development of upper-level turbulence forecast algorithms is important for enhancing flight safety. Seventeen nonconvective turbulence indices were calculated over the Tibetan Plateau for August from 2012–2021 with ERA5 reanalysis data. The thresholds for these turbulence indices were reclassified by using the percentile method based on the Richardson number. The reclassified thresholds were found to be more reasonable than the empirical thresholds. A turbulence probability index was used to aggregate the 17 turbulence indices without requiring observational data. The validity of the turbulence probability index was preliminarily confirmed by comparing it with turbulence events. Further research revealed that the turbulence probability index exhibited interannual fluctuation