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Environmental Monitoring and Assessment Oct 2023The Soil and Water Assessment Tool (SWAT) is a computational hydrological model extensively utilised for developing sustainable strategies and viable approaches for...
The Soil and Water Assessment Tool (SWAT) is a computational hydrological model extensively utilised for developing sustainable strategies and viable approaches for prudent management of water resources. The central emphasis of this study is on the utilisation of SWAT model along with SWAT-CUP (SWAT calibration toolbox) to simulate streamflow in the upper Jhelum basin, the North West Himalayas, for a period of 20 years from 2000 to 2019. The global sensitivity analysis algorithm, Sequential Uncertainty Fitting 2 (SUFI-2) of SWAT-CUP, is used for sensitivity and uncertainty analysis. The optimised parameter set estimated by SUFI-2 constitutes 11 parameters that are found to be sensitive with soil conservation service (SCS) curve number (CN) being the most influential parameter followed by snowmelt base temperature. Autocorrelation analysis using the autocorrelation function was conducted on the temperature and precipitation time series data, followed by a pre-whitening procedure to remove any autocorrelation effects. Subsequently, the modified Mann-Kendall (MMK) test was applied to examine trends in the annual temperature and precipitation data. The results indicated statistically significant positive trends in both datasets on an annual scale. The results for the calibration period (2003-2014) for monthly simulation displayed good model performance at three gauging stations, Rambiara, Sangam and Ram Munshi Bagh with R values of 0.83, 0.847, 0.829, P factor values of 0.73, 0.76, 0.75 and R factor values of 0.61, 0.58, 0.63, respectively. The validation results for monthly simulation for the 2015-2019 period showed good model agreement with R values of 0.817, 0.853, and 0.836, P factor values of 0.76, 0.8, and 0.75 and R factor values of 0.62, 0.53, and 0.65, respectively. The study concludes that the SWAT hydrological model can perform satisfactorily in high mountainous catchments and can be employed to analyse the impact of land use-land cover changes and the effect of climate variation on streamflow dynamics.
Topics: Soil; Water; Uncertainty; Environmental Monitoring; Models, Theoretical; Algorithms
PubMed: 37874405
DOI: 10.1007/s10661-023-11916-0 -
BMC Medical Informatics and Decision... Oct 2023This article focuses on the development of algorithms for a smart neurorehabilitation system, whose core is made up of artificial neural networks. The authors of the...
This article focuses on the development of algorithms for a smart neurorehabilitation system, whose core is made up of artificial neural networks. The authors of the article have proposed a completely unique transfer of ACE-R results to the CHC model. This unique approach allows for the saturation of the CHC model domains according to modified ACE-R factor analysis. The outputs of the proposed algorithm thus enable the automatic creation of a personalized and optimized neurorehabilitation plan for individual patients to train their cognitive functions. A set of tasks in 6 levels of difficulty (level 1 to level 6) was designed for each of the nine CHC model domains. For each patient, the results of the ACE-R screening helped deter-mine the specific CHC domains to be rehabilitated, as well as the initial gaming level for rehabilitation in each domain. The proposed artificial neural network algorithm was adapted to real data from 703 patients. Experimental outputs were compared to the outputs of the initially designed fuzzy expert system, which was trained on the same real data, and all outputs from both systems were statistically evaluated against expert conclusions that were available. It is evident from the conducted experimental study that the smart neurorehabilitation system using artificial neural networks achieved significantly better results than the neurorehabilitation system whose core is a fuzzy expert system. Both algorithms are implemented into a comprehensive neurorehabilitation portal (Eddie), which was supported by a research project from the Technology Agency of the Czech Republic.
Topics: Humans; Expert Systems; Fuzzy Logic; Neural Networks, Computer; Algorithms; Neurological Rehabilitation
PubMed: 37845677
DOI: 10.1186/s12911-023-02321-1 -
The Journal of Biological Chemistry Nov 2023Heavy chain-only antibodies can offer advantages of higher binding affinities, reduced sizes, and higher stabilities than conventional antibodies. To address the...
Heavy chain-only antibodies can offer advantages of higher binding affinities, reduced sizes, and higher stabilities than conventional antibodies. To address the challenge of SARS-CoV-2 coronavirus, a llama-derived single-domain nanobody C5 was developed previously that has high COVID-19 virus neutralization potency. The fusion protein C5-Fc comprises two C5 domains attached to a glycosylated Fc region of a human IgG1 antibody and shows therapeutic efficacy in vivo. Here, we have characterized the solution arrangement of the molecule. Two 1443 Da N-linked glycans seen in the mass spectra of C5-Fc were removed and the glycosylated and deglycosylated structures were evaluated. Reduction of C5-Fc with 2-mercaptoethylamine indicated three interchain Cys-Cys disulfide bridges within the hinge. The X-ray and neutron Guinier R values, which provide information about structural elongation, were similar at 4.1 to 4.2 nm for glycosylated and deglycosylated C5-Fc. To explain these R values, atomistic scattering modeling based on Monte Carlo simulations resulted in 72,737 and 56,749 physically realistic trial X-ray and neutron structures, respectively. From these, the top 100 best-fit X-ray and neutron models were identified as representative asymmetric solution structures, similar to that of human IgG1, with good R-factors below 2.00%. Both C5 domains were solvent exposed, consistent with the functional effectiveness of C5-Fc. Greater disorder occurred in the Fc region after deglycosylation. Our results clarify the importance of variable and exposed C5 conformations in the therapeutic function of C5-Fc, while the glycans in the Fc region are key for conformational stability in C5-Fc.
Topics: Humans; Immunoglobulin G; Immunoglobulin Heavy Chains; Models, Molecular; Polysaccharides; SARS-CoV-2; Antibodies, Viral; Single-Domain Antibodies
PubMed: 37838175
DOI: 10.1016/j.jbc.2023.105337 -
Journal of Trace Elements in Medicine... Dec 2023CeONPs and ZnONPs can curb the increase of cholesterol and triglycerides observed in rats with non-alcoholic fatty liver disease. It was suggested that CeO NPs could...
Nano cerium oxide and cerium/zinc nanocomposites characterization and therapeutic role in combating obesity via controlling oxidative stress and insulin resistance in rat model.
BACKGROUND
CeONPs and ZnONPs can curb the increase of cholesterol and triglycerides observed in rats with non-alcoholic fatty liver disease. It was suggested that CeO NPs could potentially have an insulin-sensitizing effect, specifically on adipose tissue and skeletal muscle. It was reported that ZnONPs combat the increase of insulin resistance observed in obese rats and could be beneficial value in NAFLD. In our previous work, ZnO-NPs manifested valuable anti-obesity effects via lowering body weight gain, oxidative stress, BMI, lipids, and insulin resistance.
METHODS
In the present study, cerium oxide nanoparticles (A-1) and cerium/zinc nanocomposites (A-2 and A-3) were synthesized by solgel to investigate their role on oxidative stress, adipocyte hormones, and insulin resistance in an obese rat model. X-ray diffraction, HRTEM, SEM, and XPS were carried out to confirm the crystal structure, the particle size, the morphology of the nanoparticles and the oxidation states.
RESULTS
The Rietveld refinement has also been executed on A-1 (chi = 1.00; average Bragg = 2.92%; R-factor = 2.45%) and on A-2 (R = 9.87%, R= 9.68%, χ = 1.04, G = 1.02). The XPS spectra indicated the presence of Ce in + 4 and + 3 oxidation states and Zn as ZnO and ZnO.OH. Cerium oxide and ZnO crystal sizes lie in the range 40.53-45.01 and 40.53-45.01 nm, respectively. The results indicated that treating obese rats with any of the tested nano compounds (5 mg or 10 mg/Kg) lowered plasma cholesterol, triglycerides, LDL, insulin resistance, glucose, and BMI significantly relative to obese group values. On the other hand, HDL increased significantly in obese rats after treatment with either A-2 or A-3 compared to obese rats. The current investigation showed antioxidant activities for A-1, A-2, and A3 as evidenced by the significant increase in GSH level and a significant decrease in MDA.
CONCLUSION
It was found that A-1, A-2, and A-3 have an efficient therapeutic role in treating of obesity-related hyperlipidemia, oxidative stress and insulin resistance. The results of A-2 and A-3 were more pronounced than those of A-1. The use of Zn/Ce nanocomposite (that have positive characteristics) in combating obesity and its complications could be become a new trend in therapeutic application for a management of obesity.
Topics: Rats; Animals; Insulin Resistance; Zinc; Zinc Oxide; Obesity; Oxidative Stress; Cerium; Nanoparticles; Cholesterol; Non-alcoholic Fatty Liver Disease; Triglycerides; Nanocomposites
PubMed: 37804595
DOI: 10.1016/j.jtemb.2023.127312 -
Annali Italiani Di Chirurgia 2023Endoscopic retrograde cholangiopancreatography (ERCP) ± endoscopic sphincterotomy, and after perforation (ERCP-P), which is a common method used for the diagnosis in...
INTRODUCTION
Endoscopic retrograde cholangiopancreatography (ERCP) ± endoscopic sphincterotomy, and after perforation (ERCP-P), which is a common method used for the diagnosis in the past and treatment today in hepatopancreatobiliary cases, is a rare complication with high mortality. While surgery has been at the forefront in perforations after ERCP in previous years, conservative treatment is widely accepted today, except for some special conditions. The aim of this study was to determine the incidence of ERCP-P in a hepatobiliary center, the outcome of the treatment modalities applied, and the risk factors for mortality due to perforations.
MATERIALS AND METHODS
Patients hospitalized in our clinic with the diagnosis of ERCP-P were retrospectively analyzed. Age, gender, ERCP indication, method of treatment applied, time between ERCP-P diagnosis and treatment, injury class, length of stay (LOS) and early results of the patients were examined.
RESULTS
45 patients were hospitalized in our clinic upon the development of ERCP-P between the years of 2006 and 2022. 37 of these patients underwent conservative and 8 patients underwent surgical treatment. When the perforation types were examined, Stapfer Type 1 was found in 4 patients, Type II in 6 patients, Type III in 3 patients and Type IV ERCP-P in 32 patients (71.1%). LOS was longer in the surgical group than in the conservative treatment group (p=0.040). Mortality was observed in 15.56% of patients. 57.1% of these patients were in the surgical group. In the multivariate analysis, the time between diagnosis and treatment of ERCP-P, which is the only factor affecting mortality, was found. The risk of death was found to be 30.61 times higher in patients with a time elapsed between ERCP-P diagnosis and treatment exceeding 24 hours compared to patients with a time elapsed ≤24 hours (p=0.030).
DISCUSSION
In our study, it was observed that the prognosis of the patients in the surgical group was poor and the length of stay was significantly longer. At the same time, the only effective factor on mortality is the time between ERCPP diagnosis and treatment.
KEY WORDS
Endoscopic Retrograde Cholangiography, Perforation, R Factors.
Topics: Humans; Cholangiopancreatography, Endoscopic Retrograde; Retrospective Studies; Sphincterotomy, Endoscopic; Risk Factors; Conservative Treatment; Intestinal Perforation; Treatment Outcome
PubMed: 37794833
DOI: No ID Found -
Faraday Discussions Jan 2024Developing batteries with energy densities comparable to internal combustion technology is essential for a worldwide transition to electrified transportation. Li-O...
Developing batteries with energy densities comparable to internal combustion technology is essential for a worldwide transition to electrified transportation. Li-O batteries are seen as the 'holy grail' of battery technologies since they have the highest theoretical energy density of all battery technologies. Current lithium-oxygen (Li-O) batteries suffer from large charge overpotentials related to the electronic resistivity of the insulating lithium peroxide (LiO) discharge product. One potential solution is the formation and stabilization of a lithium superoxide (LiO) discharge intermediate that exhibits good electronic conductivity. However, LiO is reported to be unstable at ambient temperature despite its favorable formation energy at -1.0 eV per atom. In this paper - based on our recent work on the development of cathode materials for aprotic lithium oxygen batteries including two intermetallic compounds, LiIr and LiIr, that are found to form good template interfaces with LiO - a simple goodness of fit factor to gauge how well a template surface structure can support LiO growth, is developed. The factor is a quantitative measurement to calculate the geometric difference in the unit cells of specific Miller Index 2D planes of the template surface and LiO. Using this as a guide, the factors for LiIr, LiIr, and LaNiO, are found to be good. This guide is attested by simple extension to other noble metal intermetallics with electrochemical cycling data including LiRh, LiRh, and LiPd. Finally, the template concept is extended to main group elements and the factors for LiO (111) and LiCa suggest that LiCa is a possible candidate for the template assisted LiO growth strategy.
PubMed: 37791512
DOI: 10.1039/d3fd00116d -
Toxicology in Vitro : An International... Dec 2023Cytotoxicity of some pesticides is a disadvantage for the Salmonella/microsome assay with regard to the equivalence assessment of pesticide technical grade active...
Cytotoxicity of some pesticides is a disadvantage for the Salmonella/microsome assay with regard to the equivalence assessment of pesticide technical grade active ingredients to the original products and detection of low-level impurities. The technical grade active ingredients (TGAIs) of pesticides from certain chemical classes were found to be toxic for Salmonella typhimurium strains. Among the highly cytotoxic compounds were sulfonylureas, which include 20 active ingredients. In addition, this class includes active pharmaceutical ingredients used for the manufacture of antidiabetics drugs. A traditional selection methodology was applied using the cultivation of S. typhimurium TA100 in the presence of high concentrations of thifensulfuronmethyl (TFSM) to obtain a resistant test strain insusceptible to sulfonylurea toxic effect. Two strains resistant not only to sulfonylureas (SFU) but also triazolepyrimidines were received. The first mutant strain (deposited as S. typhimurium VKPM B-14099 in the Russian National Collection of Industrial Microorganisms) demonstrated the TA100 phenotypic characteristics: hisG46, rfa, ΔuvrB-bio, pKM101. The second strain (deposited as S. typhimurium VKPM B-14359) showed the TA1535 phenotypic characteristics and probably lost the R-factor due to the selection using the poor Gm-media with TFSM. Positive controls caused pronounced mutagenic effects (±S9) in both strains, consequently the mutants did not lose the ability to respond to induction of the reverse gene mutations. The maximum non-cytotoxic concentrations of SFUs and triazole-pyrimidines for the Ames test strains did not exceed 0.05-0.125 mg/plate, while no evidence of cytotoxicity was observed for the mutants up to 5.0 mg/plate. Electron microscopy of the ultrathin sections of Salmonella cells grown with and without TFSM showed an obvious difference in the structure of the cell wall and cytoplasm in mutant and parental cultures. The concurrent resistance both to SFU and triazolepyrimidines was assumed to be mediated by the same mechanism of action of the pesticides from these classes - inhibition of acetohydroxyacid synthase. To confirm this hypothesis, the tests in the presence of branched-chain amino acids were carried out. The enrichment of agar with isoleucine prevented the toxic effects of SFU and triazolepyrimidines for all Ames test strains used in the study, while strong cytotoxicity was observed in the presence of valine and leucine. Considering the tolerance of strains both to SFU and triazolpyrimidines and the results with branched-chain amino acids, the modification of target acetohydroxyacid synthase was supposed the key to the acquired resistance. The new strains resistant to sulfonylureas and triazole-pyrimidines expands the possibilities to reveal mutagenic impurities that may occur in TGAIs in small amounts.
Topics: Mutagenicity Tests; Herbicides; Mutagens; Salmonella typhimurium; Amino Acids, Branched-Chain; Pyrimidines; Triazoles
PubMed: 37751784
DOI: 10.1016/j.tiv.2023.105699 -
British Journal of Cancer Nov 2023Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR...
BACKGROUND
Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC).
METHODS
We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS).
RESULTS
One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively.
CONCLUSION
Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies.
Topics: Humans; Neoadjuvant Therapy; Retrospective Studies; DNA Mismatch Repair; R Factors; Neoplasm Staging; Rectal Neoplasms; Chemoradiotherapy; Adenocarcinoma; Protein Deficiency
PubMed: 37749283
DOI: 10.1038/s41416-023-02444-2 -
Scientific Reports Sep 2023To explore the connection between chloroplast and coffee resistance factors, designated as S1 to S9, whole genomic DNA of 42 coffee genotypes was sequenced, and entire...
To explore the connection between chloroplast and coffee resistance factors, designated as S1 to S9, whole genomic DNA of 42 coffee genotypes was sequenced, and entire chloroplast genomes were de novo assembled. The chloroplast phylogenetic haplotype network clustered individuals per species instead of S factors. However, for the first time, it allowed the molecular validation of Coffea arabica as the maternal parent of the spontaneous hybrid "Híbrido de Timor". Individual reads were also aligned on the C. arabica reference genome to relate S factors with chloroplast metabolism, and an in-silico analysis of selected nuclear-encoded chloroplast proteins (132 proteins) was performed. The nuclear-encoded thioredoxin-like membrane protein HCF164 enabled the discrimination of individuals with and without the S9 factor, due to specific DNA variants linked to chromosome 7c (from C. canephora-derived sub-genome). The absence of both the thioredoxin domain and redox-active disulphide center in the HCF164 protein, observed in S9 individuals, raises the possibility of potential implications on redox regulation. For the first time, the identification of specific DNA variants of chloroplast proteins allows discriminating individuals according to the S profile. This study introduces an unexplored strategy for identifying protein/genes associated with S factors and candidate targets of H. vastatrix effectors, thereby creating new perspectives for coffee breeding programs.
Topics: Humans; Coffea; Coffee; Phylogeny; R Factors; Plant Breeding; Thioredoxins; Nuclear Proteins; Membrane Proteins; Chloroplast Proteins; Chloroplasts; Complement Factor H
PubMed: 37749157
DOI: 10.1038/s41598-023-41950-4 -
Computers in Biology and Medicine Nov 2023Histone deacetylase 3 (HDAC3) is an epigenetic regulator that involves gene expression, apoptosis, and cell cycle progression, and the overexpression of HDAC3 is...
Pharmacophore-based virtual screening, 3D QSAR, Docking, ADMET, and MD simulation studies: An in silico perspective for the identification of new potential HDAC3 inhibitors.
Histone deacetylase 3 (HDAC3) is an epigenetic regulator that involves gene expression, apoptosis, and cell cycle progression, and the overexpression of HDAC3 is accountable for several cancers, neurodegeneracy, and many other diseases. Therefore, HDAC3 emerged as a promising drug target for the novel drug design. Here, we carried out the pharmacophore modeling using 50 benzamide-based HDAC3 selective inhibitors and utilized it for PHASE ligand screening to retrieve the hits with similar pharmacophore features. The dataset inhibitors of best hypotheses used to build the 3D QSAR model and the generated 3D QSAR model resulted in good PLS statistics with a regression coefficient (R) of 0.89, predictive coefficient (Q) of 0.88, and Pearson-R factor of 0.94 indicating its excellent predictive ability. The hits retrieved from pharmacophore-based virtual screening were subjected to docking against HDAC3 for the identification of potential inhibitors. A total of 10 hitsM1 to M10 were ranked using their scoring functions and further subject to lead optimization. The Prime MM/GBSA, AutoDock binding free energies, and ADMET studies were implemented for the selection of lead candidates. The four ligand molecules M1, M2, M3, and M4 were identified as potential leads against HDAC3 after lead optimization. The top two leads M1 and M2 were subjected to MD simulations for their stability evaluation with HDAC3. The newly designed leads M11 and M12 were identified as HDAC3 potential inhibitors from MD simulations studies. Therefore, the outcomes of the present study could provide insights into the discovery of new potential HDAC3 inhibitors with improved selectivity and activity against a variety of cancers and neurodegenerative diseases.
Topics: Histone Deacetylase Inhibitors; Quantitative Structure-Activity Relationship; Histone Deacetylases; Molecular Docking Simulation; Humans; Molecular Dynamics Simulation; Ligands; Pharmacophore
PubMed: 37741229
DOI: 10.1016/j.compbiomed.2023.107481