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Scientific Reports Feb 2024Based on the nonlinear algorithmic theory, the R-SVM water source discrimination model and prediction method were established by using the piper qualitatively to compare...
Based on the nonlinear algorithmic theory, the R-SVM water source discrimination model and prediction method were established by using the piper qualitatively to compare the differences between the ionic components and R-type factor approximation indicator input dimensions. Taking the mine water samples of Zhaogezhuang Coal Mine as an example, according to the chemical composition analysis of the water samples from different monitoring points, six indexes of Na, Ca, Mg, Cl, SO and HCO were selected as the discrimination factors. According to the water characteristics of each aquifer and the actual needs of discrimination, the water inrush sources in the mining area were divided into four categories: The goaf water is class I, Ordovician carbonate is class II, Sandstone fracture water from the 13 coal system is class III, and Sandstone fracture water from the 12 coal system is class IV. Taking 56 typical water inrush samples as training samples, 11 groups for prediction samples, establish the input index as typical ion content, output as water source type, using SPSS statistics and MATLAB to realize the R-SVM water source discriminant analysis model, automatically establishing the mapping relationship between the water quality indexes and the evaluation standards, which can achieve the purpose of rapid and accurate discrimination of the water sample data. The results showed that the accuracy of the R-SVM model classification was 90.90% in the verification of the water source discrimination example of Zhaogezhuang mine and the coupled model has high accuracy, good applicability and discriminant ability, and has certain guiding significance for the prevention and control of water damage and the related field work.
PubMed: 38332044
DOI: 10.1038/s41598-024-53877-5 -
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 -
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 -
Nature Communications Sep 2023There is an arms race between beta-lactam antibiotics development and co-evolving beta-lactamases, which provide resistance by breaking down beta-lactam rings. We have...
There is an arms race between beta-lactam antibiotics development and co-evolving beta-lactamases, which provide resistance by breaking down beta-lactam rings. We have observed that certain beta-lactamases tend to aggregate, which persists throughout their evolution under the selective pressure of antibiotics on their active sites. Interestingly, we find that existing beta-lactamase active site inhibitors can act as molecular chaperones, promoting the proper folding of these resistance factors. Therefore, we have created Pept-Ins, synthetic peptides designed to exploit the structural weaknesses of beta-lactamases by causing them to misfold into intracellular inclusion bodies. This approach restores sensitivity to a wide range of beta-lactam antibiotics in resistant clinical isolates, including those with Extended Spectrum variants that pose significant challenges in medical practice. Our findings suggest that targeted aggregation of resistance factors could offer a strategy for identifying molecules that aid in addressing the global antibiotic resistance crisis.
Topics: Anti-Bacterial Agents; Inclusion Bodies; Monobactams; R Factors; beta-Lactamase Inhibitors; beta-Lactamases
PubMed: 37689716
DOI: 10.1038/s41467-023-41191-z -
Acta Crystallographica. Section C,... Mar 2024Beauveriolides, including the main beauveriolide I {systematic name:...
Beauveriolides, including the main beauveriolide I {systematic name: (3R,6S,9S,13S)-9-benzyl-13-[(2S)-hexan-2-yl]-6-methyl-3-(2-methylpropyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone, CHNO}, are a series of cyclodepsipeptides that have shown promising results in the treatment of Alzheimer's disease and in the prevention of foam cell formation in atherosclerosis. Their crystal structure studies have been difficult due to their tiny crystal size and fibre-like morphology, until now. Recent developments in 3D electron diffraction methodology have made it possible to accurately study the crystal structures of submicron crystals by overcoming the problems of beam sensitivity and dynamical scattering. In this study, the absolute structure of beauveriolide I was determined by 3D electron diffraction. The cyclodepsipeptide crystallizes in the space group I2 with lattice parameters a = 40.2744 (4), b = 5.0976 (5), c = 27.698 (4) Å and β = 105.729 (6)°. After dynamical refinement, its absolute structure was determined by comparing the R factors and calculating the z-scores of the two possible enantiomorphs of beauveriolide I.
Topics: Biological Products; Electrons; Crystallography, X-Ray; Hydrogen Bonding; Cordyceps
PubMed: 38411548
DOI: 10.1107/S2053229624001359 -
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 -
Scientific Reports Apr 2024Antimicrobial resistance genes (ARG), such as extended-spectrum β-lactamase (ESBL) and carbapenemase genes, are commonly carried on plasmids. Plasmids can transmit...
Antimicrobial resistance genes (ARG), such as extended-spectrum β-lactamase (ESBL) and carbapenemase genes, are commonly carried on plasmids. Plasmids can transmit between bacteria, disseminate globally, and cause clinically important resistance. Therefore, targeting plasmids could reduce ARG prevalence, and restore the efficacy of existing antibiotics. Cobalt complexes possess diverse biological activities, including antimicrobial and anticancer properties. However, their effect on plasmid conjugation has not been explored yet. Here, we assessed the effect of four previously characterised bis(N-picolinamido)cobalt(II) complexes lacking antibacterial activity on plasmid conjugation in Escherichia coli and Klebsiella pneumoniae. Antimicrobial susceptibility testing of these cobalt complexes confirmed the lack of antibacterial activity in E. coli and K. pneumoniae. Liquid broth and solid agar conjugation assays were used to screen the activity of the complexes on four archetypical plasmids in E. coli J53. The cobalt complexes significantly reduced the conjugation of RP4, R6K, and R388 plasmids, but not pKM101, on solid agar in E. coli J53. Owing to their promising activity, the impact of cobalt complexes was tested on the conjugation of fluorescently tagged extended-spectrum β-lactamase encoding pCTgfp plasmid in E. coli and carbapenemase encoding pKpQILgfp plasmid in K. pneumoniae, using flow cytometry. The complexes significantly reduced the conjugation of pKpQILgfp in K. pneumoniae but had no impact on pCTgfp conjugation in E. coli. The cobalt complexes did not have plasmid-curing activity, suggesting that they target conjugation rather than plasmid stability. To our knowledge, this is the first study to report reduced conjugation of clinically relevant plasmids with cobalt complexes. These cobalt complexes are not cytotoxic towards mammalian cells and are not antibacterial, therefore they could be optimised and employed as inhibitors of plasmid conjugation.
Topics: Animals; Agar; Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactamases; Escherichia coli; Klebsiella Infections; Klebsiella pneumoniae; Mammals; Microbial Sensitivity Tests; Plasmids
PubMed: 38582880
DOI: 10.1038/s41598-024-58895-x -
Communications Biology Apr 2024Bacterial cooperation and antagonism mediated by secretion systems are among the ways in which bacteria interact with one another. Here we report the discovery of an...
Bacterial cooperation and antagonism mediated by secretion systems are among the ways in which bacteria interact with one another. Here we report the discovery of an antagonistic property of a type IV secretion system (T4SS) sourced from a conjugative plasmid, RP4, using engineering approaches. We scrutinized the genetic determinants and suggested that this antagonistic activity is independent of molecular cargos, while we also elucidated the resistance genes. We further showed that a range of Gram-negative bacteria and a mixed bacterial population can be eliminated by this T4SS-dependent antagonism. Finally, we showed that such an antagonistic property is not limited to T4SS sourced from RP4, rather it can also be observed in a T4SS originated from another conjugative plasmid, namely R388. Our results are the first demonstration of conjugative T4SS-dependent antagonism between Gram-negative bacteria on the genetic level and provide the foundation for future mechanistic studies.
Topics: Plasmids; Type IV Secretion Systems; Conjugation, Genetic; Gram-Negative Bacteria; Escherichia coli
PubMed: 38664513
DOI: 10.1038/s42003-024-06192-8 -
Communications Biology Mar 2024The increasing rate of carbapenem-resistant bacteria within healthcare environments is an issue of great concern that needs urgent attention. This resistance is driven...
The increasing rate of carbapenem-resistant bacteria within healthcare environments is an issue of great concern that needs urgent attention. This resistance is driven by metallo-β-lactamases (MBLs), which can catalyse the hydrolysis of almost all clinically available β-lactams and are resistant to all the clinically utilized β-lactamase inhibitors. In this study, an uncharacterized MBL is identified in a multidrug resistant isolate of the opportunistic pathogen, Chryseobacterium indologenes. Sequence analysis predicts this MBL (CIM-1) to be a lipoprotein with an atypical lipobox. Characterization of CIM-1 reveals it to be a high-affinity carbapenemase with a broad spectrum of activity that includes all cephalosporins and carbapenems. Results also shown that CIM-1 is potentially a membrane-associated MBL with an uncharacterized lipobox. Using prediction tools, we also identify more potentially lipidated MBLs with non-canonical lipoboxes highlighting the necessity of further investigation of lipidated MBLs.
Topics: Anti-Bacterial Agents; R Factors; beta-Lactamases; Bacterial Proteins
PubMed: 38454015
DOI: 10.1038/s42003-024-05940-0