Dextrin-aldehyde-based preparation of recyclable CDX-036 transaminase with high activity, stability and detailed characterization.

Designing an effective vaccine against different subtypes of Influenza A virus is a critical issue in the field of medical biotechnology. At the current study, a novel potential multi-epitope vaccine candidate based on the neuraminidase proteins for seven subtypes of Influenza virus was designed, using the in silico approach. Potential linear B-cell and T-cell binding epitopes from each neuraminidase protein (N1, N2, N3, N4, N6, N7, N8) were predicted by in silico tools of epitope prediction. The selected epitopes were joined by three different linkers, and physicochemical properties, toxicity, and allergenecity were investigated. The final multi-epitope construct was modeled using GalaxyWEB server, and the molecular interactions with immune receptors were investigated and the immune response simulation assay was performed. A multi-epitope construct with GPGPGPG linker with the lowest allergenicity and highest stability was selected. The molecular docking assay indicated the interactions with immune system receptors, including HLA1, HLA2, and TLR-3. Immune response simulation detected both humoral and cellular response, including the elevated count of B-cells, T-cell, and Nk-cells.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40203-021-00095-w.

Hard-to-dissolve nanofibers provide alternatives for high-efficiency and low-resistant air filtration but are limited by the universality and economics of fabrication methods. A scalable and efficient ionic solution blow-spinning strategy has herein been proposed in preparing hard-to-dissolve nanofibrous filters. The online version contains supplementary material available at 10.1007/s42765-022-00231-x.

The online version contains supplementary material available at 10.1007/s13197-021-05078-5.

Job crafting is beneficial for employees and organizations. To better predict these behaviors, we introduce the concept of job crafting self-efficacy (JCSE) and define it as an individual’s beliefs about their capability to modify the demands and resources of their job to better fit their needs. This article describes the development and validation of a scale to measure JCSE. We conducted a qualitative study to design and four quantitative studies to test the psychometric properties of this scale among Polish and American employees in both paper-and-pencil and online versions. Three independent (N1 = 364; N2 = 432; N3 = 403) confirmatory factor analyses demonstrated a good fit to a 3-factor solution comprising JCSE beliefs about increasing (a) structural job resources, (b) social job resources, and (c) challenging job demands. The 9-item JCSE Scale had good internal consistency, high time stability, and good validity. It correlated positively with general self-efficacy. JCSE explained unique variance in job crafting behaviors over and above general self-efficacy, and was more important in predicting job crafting than contextual factors. We demonstrate the role of social cognitions in shaping job redesign behaviors and provide a useful tool to evaluate the effectiveness of interventions dedicated to empowering JCSE.

The online version contains supplementary material available at 10.1007/s13205-021-02795-8.

BackgroundNon-cellular blood circulating microRNAs (plasma miRNAs) represent a promising source for the development of prognostic and diagnostic tools owing to their minimally invasive sampling, high stability, and simple quantification by standard techniques such as RT-qPCR. So far, the majority of association studies involving plasma miRNAs were disease-specific case-control analyses. In contrast, in the present study, plasma miRNAs were analysed in a sample of 372 individuals from a population-based cohort study, the Study of Health in Pomerania (SHIP).MethodsQuantification of miRNA levels was performed by RT-qPCR using the Exiqon Serum/Plasma Focus microRNA PCR Panel V3.M covering 179 different miRNAs. Of these, 155 were included in our analyses after quality-control. Associations between plasma miRNAs and the phenotypes age, body mass index (BMI), and sex were assessed via a two-step linear regression approach per miRNA. The first step regressed out the technical parameters and the second step determined the remaining associations between the respective plasma miRNA and the phenotypes of interest.ResultsAfter regressing out technical parameters and adjusting for the respective other two phenotypes, 7, 15, and 35 plasma miRNAs were significantly (q < 0.05) associated with age, BMI, and sex, respectively. Additional adjustment for the blood cell parameters identified 12 and 19 miRNAs to be significantly associated with age and BMI, respectively. Most of the BMI-associated miRNAs likely originate from liver. Sex-associated differences in miRNA levels were largely determined by differences in blood cell parameters. Thus, only 7 as compared to originally 35 sex-associated miRNAs displayed sex-specific differences after adjustment for blood cell parameters.ConclusionsThese findings emphasize that circulating miRNAs are strongly impacted by age, BMI, and sex. Hence, these parameters should be considered as covariates in association studies based on plasma miRNA levels. The established experimental and computational workflow can now be used in future screening studies to determine associations of plasma miRNAs with defined disease phenotypes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0136-7) contains supplementary material, which is available to authorized users.

This study aims to explore the effect of Artemisia argyi Levl.et Vant. (AAL) on the intestinal microbiota in UC mice and the possible mechanism of AAL in alleviating UC, providing new scientific evidence for clinical application. The chemical ingredients of AAL aqueous extract were analyzed using ultra-performance liquid chromatography Q-exactive mass spectrometry (UHPLC-QE-MS) non-target metabolomics. UC model mice were induced by 3% dextran sulfate sodium (DSS) to observe the ameliorative effect of AAL on colonic inflammation in UC mice. Mouse intestinal microbial diversity, community composition, and community function were analyzed using 16 S rRNA gene sequencing, linear discriminant analysis effect size (LEfSe), and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). The key targets of AAL for UC treatment were clarified using network pharmacology. The binding activities of AAL characteristic ingredients and core targets were matched by molecular docking technology. Finally, the mechanism of AAL treatment for UC was confirmed by immunohistochemistry (IHC) assay. UHPLC-QE-MS non-target metabolomics showed that the active ingredients of AAL aqueous extract with high stability and reliability can be detected in both positive and negative ion modes. AAL can alleviate colonic inflammation and reduce pathological damage to colonic tissues in UC mice. Intestinal microbial community analysis demonstrated that AAL can restore intestinal flora imbalance in UC mice by increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria. Network pharmacology revealed that TNF-α, IL-6, IL-1β, PTGS2, and ESR1 are key targets of AAL for UC treatment. The molecular docking results showed that 1,8-cineole and borneol formed stable complexes with all five core targets, and the complexes had high binding affinity. IHC assays showed that AAL inhibited the activation of IL-17 signaling pathway and regulated the ferroptosis pathway by down-regulating IL-17 A, IL-17RA, Act1, TRAF6, and PTGS2 expression and up-regulating GPX4 expression. AAL alleviates DSS-induced UC by synergistically inhibiting the inflammatory response, regulating intestinal flora dysbiosis, modulating the IL-17 signaling pathway, and suppressing the ferroptosis pathway. These findings preliminarily elucidate the mechanism of AAL in alleviating UC and potentially provide a theoretical basis for the clinical treatment of UC and the development of new drugs.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-20655-w.

Metal-organic frameworks (MOFs) are promising heterogeneous catalysts or catalyst support materials for biodiesel production due to their high surface area, tunable porosity, and diverse morphology. However, developing bimetallic MOFs that combine easy scalability, high stability, and good catalytic activity that are beneficial for large-scale synthesis and applications is still highly desirable. Herein, a fascinating bimetallic Bi/Ce-MOFs (Bi/Ce-BTC) supported heteropolyacid (HPMo) was constructed by a simple hydrothermal synthesis strategy, and its catalytic performance was evaluated in the esterification of oleic acid. A comprehensive characterization of the composite material’s structure, composition, and properties was performed using various techniques (XRD, FTIR, N2 physisorption, SEM-EDS, TG, NH3-TPD, Py-FTIR, and XPS). These characterization techniques thoroughly confirm the successful impregnation of HPMo on the Bi/Ce-BTC, and it possesses a relatively large specific surface area, meso-porosity, high acidity capacity, and synergistic catalytic effect between the substrates. Catalytic experiments demonstrated that HPMo@Bi/Ce-BTC exhibited the best catalytic performance, achieving 92.7% conversion of oleic acid under optimal reaction conditions. Remarkably, the catalyst could be easily reused six times with an acceptable oleic acid conversion (79.3%). In addition, the kinetic analysis of the esterification reaction by HPMo@Bi/Ce-BTC catalyst showed pseudo-first-order kinetics, with activation energies found to be 60.9 kJ/mol. Overall, the employment of bimetallic MOFs for impregnation of active species paves a potential way for broad applications in sustainable chemical processes.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s13065-025-01662-4.

BackgroundNumerous organisms have evolved a wide range of toxic peptides for self-defense and predation. Their effective interstitial and macro-environmental use requires energetic and structural stability. One successful group of these peptides includes a tri-disulfide domain arrangement that offers toxicity and high stability. Sequential tri-disulfide connectivity variants create highly compact disulfide folds capable of withstanding a variety of environmental stresses. Their combination of toxicity and stability make these peptides remarkably valuable for their potential as bio-insecticides, antimicrobial peptides and peptide drug candidates. However, the wide sequence variation, sources and modalities of group members impose serious limitations on our ability to rapidly identify potential members. As a result, there is a need for automated high-throughput member classification approaches that leverage their demonstrated tertiary and functional homology.ResultsWe developed an SVM-based model to predict sequential tri-disulfide peptide (STP) toxins from peptide sequences. One optimized model, called PredSTP, predicted STPs from training set with sensitivity, specificity, precision, accuracy and a Matthews correlation coefficient of 94.86 %, 94.11 %, 84.31 %, 94.30 % and 0.86, respectively, using 200 fold cross validation. The same model outperforms existing prediction approaches in three independent out of sample testsets derived from PDB.ConclusionPredSTP can accurately identify a wide range of cystine stabilized peptide toxins directly from sequences in a species-agnostic fashion. The ability to rapidly filter sequences for potential bioactive peptides can greatly compress the time between peptide identification and testing structural and functional properties for possible antimicrobial and insecticidal candidates. A web interface is freely available to predict STP toxins from http://crick.ecs.baylor.edu/.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0633-x) contains supplementary material, which is available to authorized users.

Viruses of the picornavirus-like supercluster mainly achieve cleavage of polyproteins into mature proteins through viral 3-chymotrypsin proteases (3Cpro) or 3-chymotrypsin-like proteases (3CLpro). Due to the essential role in processing viral polyproteins, 3Cpro/3CLpro is a drug target for treating viral infections. The 3CLpro is considered the main protease (Mpro) of coronaviruses. In the current study, the SARS-CoV-2 Mpro inhibitory activity of di- and tri-peptides (DTPs) resulted from the proteolysis of bovine milk proteins was evaluated. A set of 326 DTPs were obtained from virtual digestion of bovine milk major proteins. The resulted DTPs were screened using molecular docking. Twenty peptides (P1–P20) showed the best binding energies (ΔGb < − 7.0 kcal/mol). Among these 20 peptides, the top five ligands, namely P1 (RVY), P3 (QSW), P17 (DAY), P18 (QSA), and P20 (RNA), based on the highest binding affinity and the highest number of interactions with residues in the active site of Mpro were selected for further characterization by ADME/Tox analyses. For further validation of our results, molecular dynamics simulation was carried out for P3 as one of the most favorable candidates for up to 100 ns. In comparison to N3, a peptidomimetic control inhibitor, high stability was observed as supported by the calculated binding energy of the Mpro-P3 complex (− 59.48 ± 4.87 kcal/mol). Strong interactions between P3 and the Mpro active site, including four major hydrogen bonds to HIS41, ASN142, GLU166, GLN189 residues, and many hydrophobic interactions from which the interaction with CYS145 as a catalytic residue is worth mentioning. Conclusively, milk-derived bioactive peptides, especially the top five selected peptides P1, P3, P17, P18, and P20, show promise as an antiviral lead compound.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10989-021-10284-y.

BackgroundNext-generation sequencing technologies enable the re-sequencing of a large number of genomes and provide an unprecedented opportunity to discover numerous DNA polymorphisms throughout the genome of a species. As the second most abundant form of genetic variation, InDels, with characteristics of co-dominance, multiple alleles and high stability and density and that are easy to genotype, have received an increasing amount attention.ResultsIn this work, a total of 2,329,544 InDels were identified in 1767 rice genomes; these InDels were dispersed across all 12 rice chromosomes, with one InDel marker found, on average, every 160.22 bp. There were 162,380 highly polymorphic InDels with a polymorphism information content (PIC) ≥ 0.5, contributing 1.81 % to the unique primer set. Of these highly polymorphic InDels, we also selected InDels with major allele differences (the size difference between the most and second most frequent alleles) ≥ 3 bp or 8 bp for primer design, which provided a more flexible choice for researchers. Finally, we experimentally validated 100 highly polymorphic InDels for accuracy and polymorphism. The PCR results showed that the accuracy of the InDel markers was 95.70 %, while the average PIC value was 0.56, with a range of 0.19 to 0.78; the average allele number was 3.02, with a range of 2 to 5.ConclusionsOur genome-wide and easily used InDel markers with high polymorphism and density in both cultivated and wild rice will undoubtedly have practical implications in rice marker-assisted breeding and will also meet the need of fine-scale genetic mapping in map-based rice gene cloning.Electronic supplementary materialThe online version of this article (doi:10.1186/s12284-015-0063-4) contains supplementary material, which is available to authorized users.

BackgroundDNA methylation is thought to play an important role in the regulation of mammalian gene expression, partly based on the observation that a lack of CpG island methylation in gene promoters is associated with high transcriptional activity. However, the CpG island methylation level only accounts for a fraction of the variance in gene expression, and methylation in other domains is hypothesized to play a role. We hypothesized that regions of very high stability in methylation would exist and provide biological insight into the role of methylation both within and outside CpG islands.ResultsWe set out to identify highly stable regions in the human methylome, based on the subset of CpGs assayed with an Illumina Infinium 450 K array. Using 1,737 samples from 30 publically available studies, we identified 15,224 CpGs that are ‘ultrastable’ in their state across tissues and developmental stages (974 always methylated; 14,250 always unmethylated). Further analysis of ultrastable CpGs led us to identify a novel subset of CpG islands, ‘ravines’, which exhibit a markedly consistent pattern of low methylation with highly methylated flanking shores and shelves. We distinguish ravines from other CpG islands characterized by a broader flanking region of low methylation. Interestingly, ravines are associated with higher gene expression compared to typical unmethylated CpG islands, and are more often found near housekeeping genes.ConclusionsThe identification of ultrastable sites in the human methylome led us to identify a subclass of CpG islands characterized by a very stable pattern of methylation encompassing the island and flanking regions, established early in development and maintained through differentiation. This pattern is associated with particularly high levels of gene expression, providing new evidence that methylation beyond the CpG island could play a role in gene expression.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-8935-7-28) contains supplementary material, which is available to authorized users.

Background6-[Bis(carboxymethyl)amino]-1,4-bis(carboxymethyl)-6-methyl-1,4-diazepane (AAZTA ) is a promising chelator with potential advantages over 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for radiopharmaceutical applications. Its mesocyclic structure enables fast radiolabelling under mild conditions with trivalent metals including not only 68Ga for positron emission tomography (PET) but also 177Lu and 111In for single-photon emission computed tomography (SPECT) and radionuclide therapy. Here, we describe the evaluation of a bifunctional AAZTA derivative conjugated to a model minigastrin derivative as a potential theranostic agent.MethodsAn AAZTA derivative with an aliphatic C9 chain as linker was coupled to a minigastrin, namely [AAZTA0, D-Glu1, desGlu2–6]-minigastrin (AAZTA-MG), and labelled with 68Ga, 177Lu and 111In. The characterisation in vitro included stability studies in different media and determination of logD (octanol/PBS). Affinity determination (IC50) and cell uptake studies were performed in A431-CCK2R cells expressing the human CCK2 receptor. μPET/CT and ex vivo biodistribution studies were performed in CCK2 tumour xenograft-bearing nude mice and normal mice.ResultsAAZTA-MG showed high radiochemical yields for 68Ga (>95 %), 177Lu (>98 %) and 111In (>98 %). The logD value of −3.7 for both [68Ga]- and [177Lu]-AAZTA-MG indicates a highly hydrophilic character. Stability tests showed overall high stability in solution with some degradation in human plasma for [68Ga]- and transchelation towards DTPA for and [177Lu]-AAZTA-MG. An IC50 value of 10.0 nM was determined, which indicates a high affinity for the CCK2 receptor. Specific cell uptake after 60 min was >7.5 % for [68Ga]-AAZTA-MG and >9.5 % for [177Lu]-AAZTA-MG, comparable to other DOTA-MG-analogues. μPET/CT studies in CCK2 receptor tumour xenografted mice not only revealed high selective accumulation in A431-CCK2R positive tumours of 68Ga-labelled AAZTA-MG (1.5 % ID/g in 1 h post injection) but also higher blood levels as corresponding DOTA-analogues. The 111In-labelled peptide had a tumour uptake of 1.7 % ID/g. Biodistribution in normal mice with the [177Lu]-AAZTA-MG showed a considerable uptake in intestine (7.3 % ID/g) and liver (1.5 % ID/g).ConclusionOverall, AAZTA showed interesting properties as bifunctional chelator for peptides providing mild radiolabelling conditions for both 68Ga and trivalent metals having advantages over the currently used chelator DOTA. Studies are ongoing to further investigate in vivo targeting properties and stability issues and the influence of spacer length on biodistribution of AAZTA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0154-7) contains supplementary material, which is available to authorized users.

MammaPrint is an FDA-cleared microarray-based test that uses expression levels of the 70 MammaPrint genes to assess distant recurrence risk in early-stage breast cancer. The prospective RASTER study proved that MammaPrint Low Risk patients can safely forgo chemotherapy, which is further subject of the prospective randomized MINDACT trial. While MammaPrint diagnostic results are obtained from mini-arrays, clinical trials may be performed on whole-genome arrays. Here we demonstrate the equivalence and reproducibility of the MammaPrint test. MammaPrint indices were collected for breast cancer samples: (i) on both customized certified array types (n = 1,897 sample pairs), (ii) with matched fresh and FFPE tissues (n = 552 sample pairs), iii) for control samples replicated over a period of 10 years (n = 11,333), and iv) repeated measurements (n = 280). The array type indicated a near perfect Pearson correlation of 0.99 (95 % CI: 0.989–0.991). Paired fresh and FFPE samples showed an excellent Pearson correlation of 0.93 (95 % CI 0.92–0.94), in spite of the variability introduced by intratumoral tissue heterogeneity. Control samples showed high consistency over 10 year's time (overall reproducibility of 97.4 %). Precision and repeatability are overall 98.2 and 98.3 %, respectively. Results confirm that the combination of the near perfect correlation between array types, excellent equivalence between tissue types, and a very high stability, precision, and repeatability demonstrate that results from clinical trials (such as MINDACT and I-SPY 2) are equivalent to current MammaPrint FFPE and fresh diagnostics, and can be used interchangeably.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-016-3764-5) contains supplementary material, which is available to authorized users.

A novel label-free surface plasmon resonance (SPR) aptasensor has been constructed for the detection of N-gene of SARS-CoV-2 by using thiol-modified niobium carbide MXene quantum dots (Nb2C-SH QDs) as the bioplatform for anchoring N-gene-targeted aptamer. In the presence of SARS-CoV-2 N-gene, the immobilized aptamer strands changed their conformation to specifically bind with N-gene. It thus increased the contact area or enlarged the distance between aptamer and the SPR chip, resulting in a change of the SPR signal irradiated by the laser (He-Ne) with the wavelength (λ) of 633 nm. Nb2C QDs were derived from Nb2C MXene nanosheets via a solvothermal method, followed by functionalization with octadecanethiol through a self-assembling method. Subsequently, the gold chip for SPR measurements was modified with Nb2C-SH QDs via covalent binding of the Au-S bond also by self-assembling interaction. Nb2C-SH QDs not only resulted in high bioaffinity toward aptamer but also enhanced the SPR response. Thus, the Nb2C-SH QD-based SPR aptasensor had low limit of detection (LOD) of 4.9 pg mL−1 toward N-gene within the concentration range 0.05 to 100 ng mL−1. The sensor also showed excellent selectivity in the presence of various respiratory viruses and proteins in human serum and high stability. Moreover, the Nb2C-SH QD-based SPR aptasensor displayed a vast practical application for the qualitative analysis of N-gene from different samples, including seawater, seafood, and human serum. Thus, this work can provide a deep insight into the construction of the aptasensor for detecting SARS-CoV-2 in complex environments.Graphical abstractA novel label-free surface plasmon resonance aptasensor has been constructed to detect sensitively and selectively the N-gene of SARS-CoV-2 by using thiol-modified niobium carbide MXene quantum dots as the scaffold to anchor the N-gene-targeted aptamer.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00604-021-04974-z.